fbpx
Wikipedia

Tianeptine

January 01, 1970

Tianeptine, sold under the brand names Stablon, Tatinol, and Coaxil among others, is an atypical tricyclic antidepressant which is used mainly in the treatment of major depressive disorder, although it may also be used to treat anxiety, asthma, and irritable bowel syndrome.[3][4][5]

Tianeptine
Clinical data
Trade namesStablon, Coaxil, Tatinol
Other namesTia;[1] ZaZa;[2] S-1574;[3][4][5] JNJ-39823277; TPI-1062[6]
AHFS/Drugs.comInternational Drug Names
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability99%[9][10]
Protein binding95%[10]
MetabolismHepatic[10] by β-oxidation[12]
Elimination half-life2.5–3 hours[9][10]
4–9 hours (elderly)[10][11]
ExcretionUrine: 65%[9]
Feces: 15%[10]
Identifiers
  • 7-[(3-Chloro-6-methyl-5,5-dioxo-11H-benzo[c][2,1]benzothiazepin-11-yl)amino]heptanoic acid
CAS Number
PubChem CID
  • 68870
IUPHAR/BPS
  • 7558
ChemSpider
  • 62102 Y
UNII
  • 0T493YFU8O
KEGG
  • D02575 Y
ChEBI
  • CHEBI:91749
ChEMBL
  • ChEMBL1289110 N
CompTox Dashboard (EPA)
  • DTXSID7048295
ECHA InfoCard100.131.750 100.069.844, 100.131.750
Chemical and physical data
FormulaC21H25ClN2O4S
Molar mass436.95 g·mol−1
3D model (JSmol)
  • Interactive image
  • Clc1cc2c(cc1)C(c3c(N(C)S2(=O)=O)cccc3)NCCCCCCC(=O)O
  • InChI=1S/C21H24ClN2NaO4S/c1-24-18-9-6-5-8-16(18)21(23-13-7-3-2-4-10-20(25)26)17-12-11-15(22)14-19(17)29(24,27)28/h5-6,8-9,11-12,14,21,23H,2-4,7,10,13H2,1H3,(H,25,26) Y
  • Key:JICJBGPOMZQUBB-UHFFFAOYSA-N Y
 NY (what is this?)  (verify)

Tianeptine has antidepressant and anxiolytic effects[13] with a relative lack of sedative, anticholinergic, and cardiovascular side effects.[10][14] It has been found to act as an atypical agonist of the μ-opioid receptor with clinically negligible effects on the δ- and κ-opioid receptors.[15][16][17] This may explain part of its antidepressant and anxiolytic effects; however, it is thought that tianeptine also modulates glutamate receptors, and this may also explain tianeptine's antidepressant/anxiolytic effects.

Tianeptine was discovered and patented by the French Society of Medical Research in the 1960s. Currently, tianeptine is approved in France and manufactured and marketed by Laboratories Servier SA; it is also marketed in a number of other European countries under the trade name Coaxil as well as in Asia (including Singapore) and Latin America as Stablon and Tatinol but it is not available in Australia, Canada, New Zealand, or the United Kingdom.[18][19] In the US, it is an unregulated drug sold under several names and some of these products have been found to be adulterated with other recreational drugs.[20]

Medical uses edit

Depression and anxiety edit

Tianeptine shows efficacy against serious depressive episodes (major depression), comparable to amitriptyline, imipramine and fluoxetine, but with significantly fewer side effects.[18] It was shown to be more effective than maprotiline in a group of people with co-existing depression and anxiety.[10] Tianeptine also displays significant anxiolytic properties and is useful in treating a spectrum of anxiety disorders including panic disorder, as evidenced by a study in which those administered 35% CO2 gas (carbogen) on paroxetine or tianeptine therapy showed equivalent panic-blocking effects.[21] Like many antidepressants (including bupropion, the selective serotonin reuptake inhibitors, the serotonin-norepinephrine reuptake inhibitors, moclobemide and numerous others) it may also have a beneficial effect on cognition in people with depression-induced cognitive dysfunction.[22] A 2005 study in Egypt showed tianeptine to be effective in men with depression and erectile dysfunction.[23]

Tianeptine has been found to be effective in depression, in people with Parkinson's disease,[24] and with post-traumatic stress disorder[25] for which it was as safe and effective as fluoxetine and moclobemide.[26]

Other uses edit

A clinical trial comparing its efficacy and tolerability with amitriptyline in the treatment of irritable bowel syndrome showed that tianeptine was at least as effective as amitriptyline and produced fewer prominent adverse effects, such as dry mouth and constipation.[27]

Tianeptine has been reported to be very effective for asthma. In August 1998, Dr. Fuad Lechin and colleagues at the Central University of Venezuela Institute of Experimental Medicine in Caracas published the results of a 52-week randomized controlled trial of asthmatic children; the children in the groups who received tianeptine had a sharp decrease in clinical rating and increased lung function.[28] Two years earlier, they had found a close, positive association between free serotonin in plasma and severity of asthma in symptomatic persons.[28] As tianeptine was the only agent known to both reduce free serotonin in plasma and enhance uptake in platelets, they decided to use it to see if reducing free serotonin levels in plasma would help.[28] By November 2004, there had been two double-blind placebo-controlled crossover trials and an under-25,000 person open-label study lasting over seven years, both showing effectiveness.[28]

Tianeptine also has anticonvulsant and analgesic effects,[29] and a clinical trial in Spain that ended in January 2007 has shown that tianeptine is effective in treating pain due to fibromyalgia.[30] Tianeptine has been shown to have efficacy with minimal side effects in the treatment of attention-deficit hyperactivity disorder.[31]

Contraindications edit

Known contraindications include the following:[32]

  • Hypersensitivity to tianeptine or any of the tablet's excipients.[33]

Side effects edit

Compared to other tricyclic antidepressants, it produces significantly fewer cardiovascular, anticholinergic (like dry mouth or constipation), sedative and appetite-stimulating effects.[14][18] Unlike other tricyclic antidepressants, tianeptine does not affect heart function.[34] μ-Opioid receptor agonists can sometimes induce euphoria, as does tianeptine, occasionally, at high doses, well above the normal therapeutic range. Tianeptine can also cause severe withdrawal symptoms after prolonged use at high doses which should prompt extreme caution.[35][36]

By frequency edit

Sources:[10][14][37]

Common (>1% frequency)
  • Headache (up to 18%)
  • Dizziness (up to 10%)
  • Insomnia/nightmares (up to 20%)
  • Drowsiness (up to 10%)
  • Dry mouth (up to 20%)
  • Constipation (up to 15%)
  • Nausea
  • Abdominal pain
  • Weight gain (~3%)
  • Agitation
  • Anxiety/irritability
Uncommon (0.1–1% frequency)
Rare (<0.1% frequency)

Pharmacology edit

Pharmacodynamics edit

See also: Pharmacology of antidepressants and Tricyclic antidepressant § Binding profiles
Tianeptine[39]
Site Ki (nM) Species Ref
MORTooltip μ-Opioid receptor 383–768 (Ki)
194 (EC50Tooltip Half-maximal effective concentration)		 Human [15][39]
[15]
DORTooltip δ-Opioid receptor >10,000 (Ki)
37,400 (EC50)		 Human [15][39]
[15]
KORTooltip κ-Opioid receptor >10,000 (Ki)
100,000 (EC50)		 Human [15][39]
[15]
SERTTooltip Serotonin transporter >10,000 Human [39]
NETTooltip Norepinephrine transporter >10,000 Human [39]
DATTooltip Dopamine transporter >10,000 Human [39]
5-HT1A >10,000 Human [39]
5-HT1B >10,000 Human [39]
5-HT1D >10,000 Human [39]
5-HT1E >10,000 Human [39]
5-HT2A >10,000 Human [39]
5-HT2B >10,000 Human [39]
5-HT2C >10,000 Human [39]
5-HT3 >10,000 Human [39]
5-HT5A >10,000 Human [39]
5-HT6 >10,000 Human [39]
5-HT7 >10,000 Human [39]
α1A >10,000 Human [39]
α1B >10,000 Human [39]
α2A >10,000 Human [39]
α2B >10,000 Human [39]
α2C >10,000 Human [39]
β1 >10,000 Human [39]
β2 >10,000 Human [39]
D1 >10,000 Human [39]
D2 >10,000 Human [39]
D3 >10,000 Human [39]
D4 >10,000 Human [39]
D5 >10,000 Human [39]
H1 >10,000 Human [39]
H2 >10,000 Human [39]
H3 >10,000 Human [39]
H4 >10,000 Human [39]
mAChTooltip Muscarinic acetylcholine receptor >10,000 Human [39]
σ1 >10,000 Guinea pig [39]
σ2 >10,000 Rat [39]
I1 >10,000 Human [39]
A1 >10,000 (EC50) Human [15]
VDCCTooltip Voltage-dependent calcium channel >10,000 Human [39]
Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug interacts with the site.

Atypical μ-opioid receptor agonist edit

In 2014, tianeptine was found to be a μ-opioid receptor (MOR) full agonist using human proteins.[15] It was also found to act as a full agonist of the δ-opioid receptor (DOR), although with approximately 200-fold lower potency.[15] The same researchers subsequently found that the MOR is required for the acute and chronic antidepressant-like behavioral effects of tianeptine in mice and that its primary metabolite had similar activity as a MOR agonist but with a much longer elimination half-life.[40] Moreover, in mice, although tianeptine produced other opioid-like behavioral effects such as analgesia and reward, it did not result in tolerance or withdrawal.[40] The authors suggested that tianeptine may be acting as a biased agonist of the MOR and that this may be responsible for its atypical profile as a MOR agonist.[40] However, there are reports that suggest that withdrawal effects resembling those of other typical opioid drugs (including but not limited to depression, insomnia, and cold/flu-like symptoms) do manifest following prolonged use at dosages far beyond the medical range.[41][42] In addition to its therapeutic effects, activation of the MOR is likely to also be responsible for the abuse potential of tianeptine at high doses that are well above the normal therapeutic range and efficacy threshold.

In rats, when co-administered with morphine, tianeptine prevents morphine-induced respiratory depression without impairing analgesia.[43] In humans, however, tianeptine was found to increase respiratory depression when administered in conjunction with the potent opioid remifentanil.[44]

Glutamatergic, neurotrophic, and neuroplastic modulation edit

Research suggests that tianeptine produces its antidepressant effects through indirect alteration and inhibition of glutamate receptor activity (i.e., AMPA receptors and NMDA receptors) and release of BDNFTooltip brain-derived neurotrophic factor, in turn affecting neural plasticity.[45][46][47][48][14][18] Some researchers hypothesize that tianeptine has a protective effect against stress induced neuronal remodeling.[45][14] There is also action on the NMDA and AMPA receptors.[45][14] In animal models, tianeptine inhibits the pathological stress-induced changes in glutamatergic neurotransmission in the amygdala and hippocampus. It may also facilitate signal transduction at the CA3 commissural associational synapse by altering the phosphorylation state of glutamate receptors. With the discovery of the rapid and novel antidepressant effects of drugs such as ketamine, many believe the efficacy of antidepressants is related to promotion of synaptic plasticity. This may be achieved by regulating the excitatory amino acid systems that are responsible for changes in the strength of synaptic connections as well as enhancing BDNF expression, although these findings are based largely on preclinical studies.[18]

Serotonin reuptake enhancer edit

Tianeptine is no longer labelled a selective serotonin reuptake enhancer (SSRE) antidepressant.[45][46][47][48][14][18] Tianeptine had been found to bind to the same allosteric site on the serotonin transporter (SERT) as conventional TCAs.[49] However, whereas conventional TCAs inhibit serotonin reuptake by the SERT, tianeptine appeared to enhance it.[49] This seems to be because of the unique C3 amino heptanoic acid side chain of tianeptine, which, in contrast to other TCAs, is thought to lock the SERT in a conformation that increases affinity for and reuptake (Vmax) of serotonin.[49] As such, tianeptine was thought to act a positive allosteric modulator of the SERT, or as a "serotonin reuptake enhancer".[49]

Although tianeptine was originally found to have no effect in vitro on monoamine reuptake, release, or receptor binding, upon acute and repeated administration, tianeptine decreased the extracellular levels of serotonin in rat brain without a decrease in serotonin release, leading to a theory of tianeptine enhancing serotonin reuptake.[50] The (−)-enantiomer is more active in this sense than the (+)-enantiomer.[51] However, more recent studies found that long-term administration of tianeptine does not elicit any marked alterations (neither increases nor decreases) in extracellular levels of serotonin in rats.[45] However, coadministration of tianeptine and the selective serotonin reuptake inhibitor fluoxetine inhibited the effect of tianeptine on long-term potentiation in hippocampal CA1 area. This is considered an argument for the opposite effects of tianeptine and fluoxetine on serotonin uptake,[14] although it has been shown that fluoxetine can be partially substituted for tianeptine in animal studies.[52] In any case, the collective research suggests that direct modulation of the serotonin system is unlikely to be the mechanism of action underlying the antidepressant effects of tianeptine.[49]

Other actions edit

Tianeptine modestly enhances the mesolimbic release of dopamine[53] and potentiates CNS D2 and D3 receptors.[54] Tianeptine has no affinity for the dopamine transporter or the dopamine receptors.[45] CREB-TF (CREB, cAMP response element-binding protein)[55] is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the genes.[56] CREB has a well-documented role in neuronal plasticity and long-term memory formation in the brain. Cocaine- and amphetamine-regulated transcript, also known as CART, is a neuropeptide protein that in humans is encoded by the CARTPT gene.[57][58] CART appears to have roles in reward, feeding, stress,[59] and it has the functional properties of an endogenous psychostimulant.[60] Taking into account that CART production is upregulated by CREB,[61] it could be hypothesized that due to tianeptine's central role in BDNF and neuronal plasticity, this CREB may be the transcription cascade through which this drug enhances mesolimbic release of dopamine.

Research indicates possible anticonvulsant (anti-seizure) and analgesic (painkilling) activity of tianeptine via downstream modulation of adenosine A1 receptors (as the effects could be experimentally blocked by antagonists of this receptor).[29] Tianpetine is also weak histone deacetylase inhibitor and analogs with increased potency and selectivity are developed.[62]

Pharmacokinetics edit

The bioavailability of tianeptine is approximately 99%.[9][10] Its plasma protein binding is about 95%.[10] The metabolism of tianeptine is hepatic, via β-oxidation.[10] CYP enzymes are not involved, which limits the potential for drug-drug interactions.[10] Maximal concentration is reached in about an hour and the elimination half-life is 2.5 to 3 hours.[9][10] The elimination half-life has been found to be increased to 4 to 9 hours in the elderly.[11] Tianeptine is usually packaged as a sodium salt but can also be found as tianeptine sulfate, a slower-releasing formulation patented by Janssen in 2012.[63] In 2022 Tonix Pharmaceuticals received permission from the US FDA to conduct phase II clinical trials on tianeptine hemioxalate extended-release tablets designed for once-daily use.[64] The project was discontinued in late 2023 because of disappointing results in clinical trials.

Tianeptine has two active metabolites, MC5 (a pentanoic acid derivative of the parent compound) and MC3 (a propionic acid derivative).[65][10] MC5 has a longer elimination half-life[40] of approximately 7.6 hours, and takes about a week to reach steady-state concentration under daily-dosing. MC5 is a mu-opioid agonist but not delta-opioid agonist, with EC50 at the mu-opioid receptor of 0.545 μM (vs 0.194 μM for tianeptine).[40] MC3 is a very weak mu-opioid agonist, with an EC50 of 16 μM.[40] Tianeptine is excreted 65% in the urine and 15% in feces.[9][10]

Chemistry edit

In terms of chemical structure, it is similar to tricyclic antidepressants (TCAs), but it has significantly different pharmacology and important structural differences, so it is not usually grouped with them.

Analogues edit

Although several related compounds are disclosed in the original patent,[66] no activity data are provided and it was unclear whether these share tianeptine's unique pharmacological effects. More recent structure-activity relationship studies have since been conducted, providing some further insight on μ-opioid, δ-opioid, and pharmacokinetic activity.[67][68][69][70][71] Derivatives where the aromatic chlorine substituent is replaced by bromine, iodine or methylthio, and/or the heptanoic acid tail is varied in length or replaced with other groups such as 3-methoxypropyl, show similar or increased opioid receptor activity relative to tianeptine itself.[72][73][74] Amineptine, the most closely related drug to have been widely studied, is a dopamine reuptake inhibitor with no significant effect on serotonin levels, nor opioid agonist activity. Tianeptinaline, analog of tianeptine, is a notable class I HDAC inhbitor.[62]

Society and culture edit

 
Stablon box and blister pack.

Approval and brand names edit

Brand names include:

Development edit

Under the code names JNJ-39823277 and TPI-1062, tianeptine was previously under development for the treatment of major depressive disorder in the United States and Belgium.[6] Phase I clinical trials were completed in Belgium and the United States in May and June 2009, respectively.[6] For unclear reasons development of tianeptine was discontinued in both countries in January 2012.[6] In October 2023, Tonix Pharmaceuticals announced that it had discontinued its development of tianeptine as a monotherapy for major depressive disorder after disappointing phase-2 clinical trial results.[75] An ongoing clinical trial, sponsored by the New York Psychiatric Institute, is examining tianeptine's use in treatment-resistant depression.[76]

U.S. National Poison Data System data on tianeptine showed a nationwide increase in tianeptine exposure calls and calls related to abuse and misuse during 2014–2017.[17]

Recreational use edit

As a μ-opioid agonist, tianeptine in large doses has high abuse potential. In 2001, Singapore's Ministry of Health restricted tianeptine prescribing to psychiatrists due to its recreational potential.[77]

Between 1989 and 2004, in France 141 cases of recreational use were identified, correlating to an incidence of 1 to 3 cases per 1000 persons treated with tianeptine and 45 between 2006 and 2011. According to Servier, stopping of treatment with tianeptine is difficult, due to the possibility of withdrawal symptoms in a person. The severity of the withdrawal is dependent on the daily dose, with high doses being extremely difficult to quit.[78][better source needed][79][80] An official DEA statement[81] states that the withdrawal symptoms in humans typically result in: agitation, nausea, vomiting, tachycardia, hypertension, diarrhea, tremor, and diaphoresis, similar to other opioid drugs.

In 2007, according to French Health Products Safety Agency, tianeptine's manufacturer Servier agreed to modify the drug's label, following problems with dependency.[82]

Tianeptine has been intravenously injected by drug users in Russia.[83][84] This method of administration reportedly causes an opioid-like effect and is sometimes used in an attempt to lessen opioid withdrawal symptoms.[83] Tianeptine tablets contain silica and do not dissolve completely. Often the solution is not filtered well thus particles in the injected fluid block capillaries, leading to thrombosis and then severe necrosis. Thus, in Russia tianeptine (sold under the brand name "Coaxil") is a schedule III controlled substance in the same list as the majority of benzodiazepines and barbiturates.[85]

The Centers for Disease Control and Prevention (CDC) has expressed concern that tianeptine may be an "emerging public health risk", citing an increase in exposure-related calls to poison control centers in the United States.[17] Sold retail as a dietary supplement and touted as a mood-booster and an aid for concentration, it is colloquially known as "gas-station heroin".[86] In the US, it is an unregulated drug sold under several product names and has been found to be adulterated with synthetic cannabinoid receptor agonists (SCRAs) or other drugs.[20]

A literature review conducted in 2018 found 25 articles involving 65 patients with tianeptine abuse or dependence.[35] Limited data showed that a majority of patients were male and that age ranged from 19 to 67. Routes of intake included oral, intravenous, and insufflation entry. In the 15 cases of overdose, 8 combined ingestion with at least one other substance, of which 3 resulted in death. Six additional deaths are reported involving tianeptine (making it 9 in total). In this report, the amount of tianeptine used ranged from 50 mg/day to 10 g/day orally.

Legality edit

In 2003, Bahrain classified tianeptine a controlled substance due to increasing reports of misuse and recreational use.[87]

In Russia, tianeptine (sold under the brand name "Coaxil") is a schedule III controlled substance in the same list as the majority of benzodiazepines and barbiturates.[85]

On March 13, 2020, with a decree approved by the Minister of Health, Italy became the first European country to outlaw tianeptine considering it a Class I controlled substance.[88]

United States edit

In the United States, tianeptine is not considered by the Drug Enforcement Administration as a controlled substance or analogue thereof.[89] However, its use in dietary supplements and food is unlawful.[90] The U.S. F.D.A. has issued warnings, as recently as January 2024, about the dangers of recreational tianeptine use and the risks posed by adulterated dietary supplements containing undeclared tianeptine.[91]

On 6 April 2018 Michigan became the first U.S. state to outlaw tianeptine sodium, classifying it as a schedule II controlled substance.[92] The scheduling of tianeptine sodium is effective 4 July 2018.[93]

On March 15, 2021, Alabama outlawed tianeptine, classifying it as a schedule II controlled substance.[94]

On July 1, 2022, Tennessee outlawed tianeptine and adds "any salt, sulfate, free acid, or other preparation of tianeptine, and any salt, sulfate, free acid, compound, derivative, precursor, or preparation thereof that is substantially chemically equivalent or identical with tianeptine", classifying it as a schedule II controlled substance.[95]

On December 22, 2022, Ohio outlawed tianeptine, classifying it as a schedule I controlled substance with Ohio Governor Mike DeWine referencing the widespread availability of the chemical there as "gas-station heroin."[96]

On March 23, 2023, Kentucky outlawed tianeptine, classifying it as a schedule I substance by an order of the Governor of Kentucky.[97][98]

On September 20, 2023, Florida outlawed tianeptine, classifying it as a schedule I substance by an administrative edict issued by the Florida Attorney General.[99][100][101][better source needed]

See also edit

References edit

  1. ^ Uzbekov M (2011). "FC13-09 - Antidepressant tianeptine (TIA) action is based on the acceleration of serotonin turnover in the synapse: a hypothesis". European Psychiatry. 26: 1890. doi:10.1016/S0924-9338(11)73594-5. S2CID 143885547. Retrieved 3 December 2023.
  2. ^ Wagner ML, Pergolizzi J, LeQuang JA, Breve F, Varrassi G (June 2023). "From Antidepressant Tianeptine to Street Drug ZaZa: A Narrative Review". Cureus. 15 (6): e40688. doi:10.7759/cureus.40688. PMC 10359047. PMID 37485121.
  3. ^ a b Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 1195–. ISBN 978-1-4757-2085-3.
  4. ^ a b Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. pp. 1024–. ISBN 978-3-88763-075-1.
  5. ^ a b "Tianeptine (International database)". Drugs.com.
  6. ^ a b c d "Tianeptine – AdisInsight". AdisInsight. Springer. Retrieved 31 January 2016.
  7. ^ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). from the original on 3 August 2023. Retrieved 16 August 2023.
  8. ^ "Poisons Standard June 2017". 29 May 2017.
  9. ^ a b c d e f Royer RJ, Albin H, Barrucand D, Salvadori-Failler C, Kamoun A (1988). "Pharmacokinetic and metabolic parameters of tianeptine in healthy volunteers and in populations with risk factors". Clinical Neuropharmacology. 11 (Suppl 2): S90-6. PMID 3180120.
  10. ^ a b c d e f g h i j k l m n o p Wagstaff AJ, Ormrod D, Spencer CM (March 2001). "Tianeptine: a review of its use in depressive disorders". CNS Drugs. 15 (3): 231–59. doi:10.2165/00023210-200115030-00006. PMID 11463130. S2CID 37796160.
  11. ^ a b Carlhant D, Le Garrec J, Guedes Y, Salvadori C, Mottier D, Riche C (September 1990). "Pharmacokinetics and bioavailability of tianeptine in the elderly". Drug Investigation. 2 (3): 167–172. doi:10.1007/BF03259191. S2CID 56502717.
  12. ^ Fromenty B, Freneaux E, Labbe G, Deschamps D, Larrey D, Letteron P, et al. (1 November 1989). "Tianeptine, a new tricyclic antidepressant metabolized by beta-oxidation of its heptanoic side chain, inhibits the mitochondrial oxidation of medium and short chain fatty acids in mice". Biochem Pharmacol. 38 (21): 3743–3751. doi:10.1016/0006-2952(89)90580-7. PMID 2597170.
  13. ^ Defrance R, Marey C, Kamoun A (1988). (PDF). Clinical Neuropharmacology. 11 (Suppl 2): S74-82. PMID 2902922. Archived from the original (PDF) on 4 April 2016.
  14. ^ a b c d e f g h Kasper S, McEwen BS (2008). "Neurobiological and clinical effects of the antidepressant tianeptine". CNS Drugs. 22 (1): 15–26. doi:10.2165/00023210-200822010-00002. PMID 18072812. S2CID 30330824.
  15. ^ a b c d e f g h i j Gassaway MM, Rives ML, Kruegel AC, Javitch JA, Sames D (July 2014). "The atypical antidepressant and neurorestorative agent tianeptine is a μ-opioid receptor agonist". Translational Psychiatry. 4 (7): e411. doi:10.1038/tp.2014.30. PMC 4119213. PMID 25026323.
  16. ^ Berridge KC, Kringelbach ML (August 2008). "Affective neuroscience of pleasure: reward in humans and animals". Psychopharmacology. 199 (3): 457–80. doi:10.1007/s00213-008-1099-6. PMC 3004012. PMID 18311558.
  17. ^ a b c El Zahran T, Schier J, Glidden E, Kieszak S, Law R, Bottei E, et al. (August 2018). "Characteristics of Tianeptine Exposures Reported to the National Poison Data System - United States, 2000-2017". MMWR. Morbidity and Mortality Weekly Report. 67 (30): 815–818. doi:10.15585/mmwr.mm6730a2. PMC 6072055. PMID 30070980.
  18. ^ a b c d e f Akiki T. . Glob. J. Med. Res. 13 (6). ISSN 2249-4618. Archived from the original on 3 November 2016. Retrieved 26 August 2015.
  19. ^ "Tianeptine Sodium". Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press. 5 December 2011. Retrieved 2 December 2013.
  20. ^ a b Counts CJ, Spadaro AV, Cerbini TA, Krotulski AJ, Greller HA, Nelson LS, et al. (February 2024). "Notes from the Field: Cluster of Severe Illness from Neptune's Fix Tianeptine Linked to Synthetic Cannabinoids - New Jersey, June-November 2023". MMWR. Morbidity and Mortality Weekly Report. 73 (4): 89–90. doi:10.15585/mmwr.mm7304a5. PMC 10843069. PMID 38300852.
  21. ^ Schruers K, Griez E (December 2004). "The effects of tianeptine or paroxetine on 35% CO2 provoked panic in panic disorder". Journal of Psychopharmacology. 18 (4): 553–8. doi:10.1177/0269881104047283. PMID 15582922. S2CID 26981110.
  22. ^ Baune BT, Renger L (September 2014). "Pharmacological and non-pharmacological interventions to improve cognitive dysfunction and functional ability in clinical depression--a systematic review". Psychiatry Research. 219 (1): 25–50. doi:10.1016/j.psychres.2014.05.013. PMID 24863864. S2CID 23684657.
  23. ^ El-Shafey H, Atteya A, Abu El-Magd S, Hassanein A, Fathy A, Shamloul R (September 2006). "Tianeptine can be effective in men with depression and erectile dysfunction". The Journal of Sexual Medicine. 3 (5): 910–917. doi:10.1111/j.1743-6109.2005.00141.x. PMID 16942535.
  24. ^ Levin OS (May 2007). "Coaxil (tianeptine) in the treatment of depression in Parkinson's disease". Neuroscience and Behavioral Physiology. 37 (4): 419–24. doi:10.1007/s11055-007-0029-0. PMID 17457538. S2CID 7637174.
  25. ^ Aleksandrovskiĭ I, Avedisova AS, Boev IV, Bukhanovkskiĭ AO, Voloshin VM, Tsygankov BD, et al. (2005). "[Efficacy and tolerability of coaxil (tianeptine) in the therapy of posttraumatic stress disorder]" Эффективность и переносимость коаксила (тианептина) при терапии посттравматического стрессового расстройства [Efficacy and tolerability of coaxil (tianeptine) in the therapy of posttraumatic stress disorder]. Zhurnal Nevrologii I Psikhiatrii Imeni S.S. Korsakova (in Russian). 105 (11): 24–9. PMID 16329631.
  26. ^ Onder E, Tural U, Aker T (April 2006). "A comparative study of fluoxetine, moclobemide, and tianeptine in the treatment of posttraumatic stress disorder following an earthquake". European Psychiatry. 21 (3): 174–9. doi:10.1016/j.eurpsy.2005.03.007. PMID 15964747. S2CID 21322928.
  27. ^ Sohn W, Lee OY, Kwon JG, Park KS, Lim YJ, Kim TH, et al. (September 2012). "Tianeptine vs amitriptyline for the treatment of irritable bowel syndrome with diarrhea: a multicenter, open-label, non-inferiority, randomized controlled study". Neurogastroenterology and Motility. 24 (9): 860–e398. doi:10.1111/j.1365-2982.2012.01945.x. PMID 22679908. S2CID 2914428.
  28. ^ a b c d Lechin F, van der Dijs B, Lechin AE (November 2004). "Treatment of bronchial asthma with tianeptine". Methods and Findings in Experimental and Clinical Pharmacology. 26 (9): 697–701. doi:10.1358/mf.2004.26.9.872567. PMID 15632955.
  29. ^ a b Uzbay TI (May 2008). "Tianeptine: potential influences on neuroplasticity and novel pharmacological effects". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 32 (4): 915–24. doi:10.1016/j.pnpbp.2007.08.007. PMID 17826881. S2CID 22365299.
  30. ^ . Controlled-trials.com. Archived from the original on 21 July 2010. Retrieved 13 August 2010.
  31. ^ Niederhofer H (2004). "Tianeptine as a slightly effective therapeutic option for attention-deficit hyperactivity disorder". Neuropsychobiology. 49 (3): 130–3. doi:10.1159/000076721. PMID 15034228. S2CID 34300575.
  32. ^ (PDF). Servier Austria GmbH. 20 August 2012. Archived from the original (PDF) on 11 August 2016. Retrieved 24 February 2020.
  33. ^ Le Bricquir Y, Larrey D, Blanc P, Pageaux GP, Michel H (November 1994). "Tianeptine--an instance of drug-induced hepatotoxicity predicted by prospective experimental studies". Journal of Hepatology. 21 (5): 771–773. doi:10.1016/s0168-8278(94)80237-8. PMID 7890892.
  34. ^ Bril A, Abadie C, Ben Baouali A, Maupoil V, Rochette L (1993). "Absence of relationship between antiarrhythmic effects of antidepressant drugs and lipid peroxidation". Pharmacology. 46 (1): 23–32. doi:10.1159/000139025. PMID 8434029.
  35. ^ a b Lauhan R, Hsu A, Alam A, Beizai K (November 2018). "Tianeptine Abuse and Dependence: Case Report and Literature Review". Psychosomatics. 59 (6): 547–553. doi:10.1016/j.psym.2018.07.006. PMID 30149933. S2CID 52099752.
  36. ^ Vadachkoria D, Gabunia L, Gambashidze K, Pkhaladze N, Kuridze N (September 2009). "Addictive potential of Tianeptine - the threatening reality". Georgian Medical News (174): 92–4. PMID 19801742.
  37. ^ Waintraub L, Septien L, Azoulay P (January 2002). "Efficacy and safety of tianeptine in major depression: evidence from a 3-month controlled clinical trial versus paroxetine". CNS Drugs. 16 (1): 65–75. doi:10.2165/00023210-200216010-00005. PMID 11772119. S2CID 31125177.
  38. ^ Gülen Yıldırım S, Başterzi AD, Göka E (2004). [Tianeptine Induced Mania: A Case Report] (PDF). Klinik Psikiyatri Dergisi (in Turkish). 7 (4): 177–180. Archived from the original (PDF) on 30 June 2006.
  39. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
  40. ^ a b c d e f Samuels BA, Nautiyal KM, Kruegel AC, Levinstein MR, Magalong VM, Gassaway MM, et al. (September 2017). "The Behavioral Effects of the Antidepressant Tianeptine Require the Mu-Opioid Receptor". Neuropsychopharmacology. 42 (10): 2052–2063. doi:10.1038/npp.2017.60. PMC 5561344. PMID 28303899.
  41. ^ Springer J, Cubała WJ (March 2018). "Tianeptine Abuse and Dependence in Psychiatric Patients: A Review of 18 Case Reports in the Literature". Journal of Psychoactive Drugs. 50 (3): 275–280. doi:10.1080/02791072.2018.1438687. PMID 29494783. S2CID 3603781.
  42. ^ Marraffa JM, Stork CM, Hoffman RS, Su MK (November 2018). "Poison control center experience with tianeptine: an unregulated pharmaceutical product with potential for abuse". Clinical Toxicology. 56 (11): 1155–1158. doi:10.1080/15563650.2018.1476694. PMID 29799284. S2CID 44112801.
  43. ^ Cavalla D, Chianelli F, Korsak A, Hosford PS, Gourine AV, Marina N (August 2015). "Tianeptine prevents respiratory depression without affecting analgesic effect of opiates in conscious rats". European Journal of Pharmacology. 761: 268–72. doi:10.1016/j.ejphar.2015.05.067. PMID 26068549.
  44. ^ Algera H, van der Schrier R, Cavalla D, van Velzen M, Roozekrans M, McMorn A, et al. (October 2022). "Respiratory Effects of the Atypical Tricyclic Antidepressant Tianeptine in Human Models of Opioid-induced Respiratory Depression". Anesthesiology. 137 (4): 446–458. doi:10.1097/ALN.0000000000004324. PMID 35867853. S2CID 250989511.
  45. ^ a b c d e f McEwen BS, Chattarji S, Diamond DM, Jay TM, Reagan LP, Svenningsson P, et al. (March 2010). "The neurobiological properties of tianeptine (Stablon): from monoamine hypothesis to glutamatergic modulation". Molecular Psychiatry. 15 (3): 237–49. doi:10.1038/mp.2009.80. PMC 2902200. PMID 19704408.
  46. ^ a b McEwen BS, Chattarji S (December 2004). "Molecular mechanisms of neuroplasticity and pharmacological implications: the example of tianeptine". European Neuropsychopharmacology. 14 (Suppl 5): S497-502. doi:10.1016/j.euroneuro.2004.09.008. PMID 15550348. S2CID 21953270.
  47. ^ a b McEwen BS, Olié JP (June 2005). "Neurobiology of mood, anxiety, and emotions as revealed by studies of a unique antidepressant: tianeptine". Molecular Psychiatry. 10 (6): 525–37. doi:10.1038/sj.mp.4001648. PMID 15753957.
  48. ^ a b Brink CB, Harvey BH, Brand L (January 2006). "Tianeptine: a novel atypical antidepressant that may provide new insights into the biomolecular basis of depression". Recent Patents on CNS Drug Discovery. 1 (1): 29–41. doi:10.2174/157488906775245327. PMID 18221189. Archived from the original on 14 April 2013.
  49. ^ a b c d e Bailey SJ, Almatroudi A, Kouris A (2018). "Tianeptine: An Atypical Antidepressant with Multimodal Pharmacology" (PDF). Current Psychopharmacology. 6 (2). doi:10.2174/2211556006666170525154616. ISSN 2211-5560. S2CID 55965184.
  50. ^ Mennini T, Mocaer E, Garattini S (November 1987). "Tianeptine, a selective enhancer of serotonin uptake in rat brain". Naunyn-Schmiedeberg's Archives of Pharmacology. 336 (5): 478–82. doi:10.1007/bf00169302. PMID 3437921. S2CID 21499462.
  51. ^ Oluyomi AO, Datla KP, Curzon G (March 1997). "Effects of the (+) and (-) enantiomers of the antidepressant drug tianeptine on 5-HTP-induced behaviour". Neuropharmacology. 36 (3): 383–7. doi:10.1016/s0028-3908(97)00016-6. PMID 9175617. S2CID 11465294.
  52. ^ Alici T, Kayir H, Aygoren MO, Saglam E, Uzbay IT (January 2006). "Discriminative stimulus properties of tianeptine". Psychopharmacology. 183 (4): 446–51. doi:10.1007/s00213-005-0210-5. PMID 16292591. S2CID 5820336.
  53. ^ Invernizzi R, Pozzi L, Garattini S, Samanin R (March 1992). "Tianeptine increases the extracellular concentrations of dopamine in the nucleus accumbens by a serotonin-independent mechanism". Neuropharmacology. 31 (3): 221–7. doi:10.1016/0028-3908(92)90171-K. PMID 1630590. S2CID 21610131.
  54. ^ Dziedzicka-Wasylewska M, Rogoz Z, Skuza G, Dlaboga D, Maj J (March 2002). "Effect of repeated treatment with tianeptine and fluoxetine on central dopamine D(2) /D(3) receptors". Behavioural Pharmacology. 13 (2): 127–38. doi:10.1097/00008877-200203000-00004. PMID 11981225. S2CID 2126834.
  55. ^ Bourtchuladze R, Frenguelli B, Blendy J, Cioffi D, Schutz G, Silva AJ (October 1994). "Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein". Cell. 79 (1): 59–68. doi:10.1016/0092-8674(94)90400-6. PMID 7923378. S2CID 17250247.
  56. ^ Purves D, Augustine GJ, Fitzpatrick D, Hall WC, LaMantia AS, McNamara JO, et al. (2008). Neuroscience (4th ed.). Sinauer Associates. pp. 170–6. ISBN 978-0-87893-697-7.
  57. ^ Douglass J, Daoud S (March 1996). "Characterization of the human cDNA and genomic DNA encoding CART: a cocaine- and amphetamine-regulated transcript". Gene. 169 (2): 241–5. doi:10.1016/0378-1119(96)88651-3. PMID 8647455.
  58. ^ Kristensen P, Judge ME, Thim L, Ribel U, Christjansen KN, Wulff BS, et al. (May 1998). "Hypothalamic CART is a new anorectic peptide regulated by leptin". Nature. 393 (6680): 72–6. Bibcode:1998Natur.393...72K. doi:10.1038/29993. PMID 9590691. S2CID 4427258.
  59. ^ Zhang M, Han L, Xu Y (June 2012). "Roles of cocaine- and amphetamine-regulated transcript in the central nervous system". Clinical and Experimental Pharmacology & Physiology. 39 (6): 586–92. doi:10.1111/j.1440-1681.2011.05642.x. PMID 22077697. S2CID 25134612.
  60. ^ Kuhar MJ, Adams S, Dominguez G, Jaworski J, Balkan B (February 2002). "CART peptides". Neuropeptides. 36 (1): 1–8. doi:10.1054/npep.2002.0887. PMID 12147208. S2CID 7079530.
  61. ^ Rogge GA, Jones DC, Green T, Nestler E, Kuhar MJ (January 2009). "Regulation of CART peptide expression by CREB in the rat nucleus accumbens in vivo". Brain Research. 1251: 42–52. doi:10.1016/j.brainres.2008.11.011. PMC 2734444. PMID 19046951.
  62. ^ a b Zhao WN, Ghosh B, Tyler M, Lalonde J, Joseph NF, Kosaric N, et al. (September 2018). "Class I Histone Deacetylase Inhibition by Tianeptinaline Modulates Neuroplasticity and Enhances Memory". ACS Chemical Neuroscience. 9 (9): 2262–2273. doi:10.1021/acschemneuro.8b00116. hdl:1721.1/126372. PMID 29932631. S2CID 49389560.
  63. ^ "Tianeptine sulfate salt forms and methods of making and using the same".
  64. ^ "Tonix Pharmaceuticals Announces IND Clearance for TNX-601 ER as a Potential Treatment for Major Depressive Disorder". Tonix Pharmaceuticals Holding Corp. GlobeNewswire News Room. 3 October 2022. Retrieved 5 November 2022.
  65. ^ Szafarz M, Wencel A, Pociecha K, Fedak FA, Wlaź P, Wyska E (February 2018). "Pharmacokinetic study of tianeptine and its active metabolite MC5 in rats following different routes of administration using a novel liquid chromatography tandem mass spectrometry analytical method". Naunyn-Schmiedeberg's Archives of Pharmacology. 391 (2): 185–196. doi:10.1007/s00210-017-1448-2. PMC 5778159. PMID 29230490. S2CID 253742631.
  66. ^ FR 2104728, Malen C, Danrée B, Poignant JC, "Nouveaux dérivés tricycliques et leur procédé de préparation [Novel tricyclic derivatives and process for preparing the same]", published 1972-04-21, assigned to Science Union et CIE Societe Francaise de Recherche Medicale 
  67. ^ Kruegel AC (2015). Chemical and Biological Explorations of Novel Opioid Receptor Modulators (Thesis). Columbia University. p. 338-358. doi:10.7916/d8v1242f.
  68. ^ Labrid C, Moleyre J, Poignant JC, Malen C, Mocaër E, Kamoun A (1988). "Structure-activity relationships of tricyclic antidepressants, with special reference to tianeptine". Clinical Neuropharmacology. 11 (Suppl 2): S21–S31. PMID 3180115.
  69. ^ Sánchez-Mateo CC, Darias V, Expósito-Orta MA, Albertos LM (January 2003). "Neuropharmacological study of hetero[2,1]benzothiazepine derivatives analogues of tianeptine". Farmaco. 58 (1). Societa Chimica Italiana: 1–10. doi:10.1016/S0014-827X(02)00021-6. PMID 12595031.
  70. ^ Sánchez-Mateo CC, Darias V, Albertos LM, Expósito-Orta MA (2003). "Psychopharmacological effects of tianeptine analogous hetero[2,1] benzothiazepine derivatives". Arzneimittel-Forschung. 53 (1): 12–20. doi:10.1055/s-0031-1297064. PMID 12608009. S2CID 23593291.
  71. ^ Expósito-Orta MA, Albertos LM, Darias V, Sánchez-Mateo CC (2004). "Behavioural effects of thieno and pyrazolo [2,1] benzothiazepine derivatives in mice". Arzneimittel-Forschung. 54 (7): 365–70. doi:10.1055/s-0031-1296985. PMID 15344839. S2CID 24437547.
  72. ^ Kruegel AC (2015). Chemical and Biological Explorations of Novel Opioid Receptor Modulators (PhD thesis). Columbia University. doi:10.7916/D8V1242F.
  73. ^ US 10183919, Kruegel AC, Henke A, Gassaway MM, Rives MM, Javitch JA, Sames D, "Class of mu-opioid receptor agonists", published 2019-01-22, assigned to The Trustees of Columbia University in the City of New York 
  74. ^ WO 2017049158, Kruegel A, Sames D, Gassaway M, Javitch JA, "Carboxylic diarylthiazepineamines as mu-opioid receptor agonists", published 2017-03-23, assigned to The Trustees of Columbia University in the City of New York 
  75. ^ "Tonix Pharmaceuticals Announces Topline Results from Phase 2 Proof-of-Concept Study of TNX-601 ER for the Treatment of Major Depressive Disorder". Tonix Pharmaceuticals Holding Corp. 31 October 2023. Retrieved 2 November 2023.
  76. ^ Javitch JA (15 June 2023). "Tianeptine for Treatment Resistant Depression". Clinicaltrials.gov. Retrieved 2 November 2023.
  77. ^ World Health Organization (2001). (PDF). Archived from the original (PDF) on 17 November 2008. Retrieved 24 July 2008.
  78. ^ APM Health Europe (2007). . Archived from the original on 7 July 2011. Retrieved 24 July 2008.
  79. ^ Gibaja V (2006). (PDF). Archived from the original (PDF) on 20 July 2011. Retrieved 24 July 2008.
  80. ^ "Tianeptine (Stablon°) dans la dépression : risque trop important de dépendance". www.prescrire.org.
  81. ^ "Drug Enforcement AdministrationDiversion Control DivisionDrug & Chemical Evaluation Section - Tianeptine" (PDF).
  82. ^ French Health Products Safety Agency (Afssaps) (2007). . Archived from the original on 1 April 2008. Retrieved 24 July 2008.
  83. ^ a b Ives R (2008). (PDF). Archived from the original (PDF) on 1 December 2010. Retrieved 4 November 2008.
  84. ^ "Illicit Drug Trades in the Russian Federation" (PDF). United Nations Office on Drugs and Crime. April 2008. Retrieved 16 July 2014.
  85. ^ a b "Decision of the Government of the Russian Federation No. 681 of June 30, 1998 on the Approval of the List of Narcotic Drugs, Psychotropic Substances and Their Precursors That Shall Be Subject to Control in the Russian Federation (with Amendments and Additions)" (in Russian).
  86. ^ Hoffman J (10 January 2024). "'Gas-Station Heroin' Sold as Dietary Supplement Alarms Health Officials". The New York Times – via NYTimes.com.
  87. ^ World Health Organization (2003). (PDF). Archived from the original (PDF) on 29 June 2011. Retrieved 24 July 2008.
  88. ^ "Gazzetta Ufficiale".
  89. ^ "Tianeptine" (PDF). Office of Diversion Control at the D.E.A. Retrieved 25 May 2023.
  90. ^ "Tianeptine in Dietary Supplements". Food and Drug Administration. 22 February 2023. Retrieved 25 May 2023.
  91. ^ Musa A (24 January 2024). "FDA urges consumers not to buy tianeptine products due to serious risks as lawmakers call for "immediate action"". CNN. Retrieved 30 January 2024.
  92. ^ "Michigan approves ban on antidepressant tianeptine sodium". Associated Press – via Detroit Free Press.
  93. ^ "Public Health Code Section 333.7214.amended". Michigan Legislature. Legislative Council, State of Michigan. Retrieved 18 May 2018.[permanent dead link]
  94. ^ "New crime trend in Giles Co. after Alabama stops selling ZaZa Red, controversial stimulant". WKRN News 2. 25 May 2021. Retrieved 14 December 2022.
  95. ^ . Tennessee General Assembly. 30 March 2022. Archived from the original on 8 April 2022.
  96. ^ "Governor DeWine Authorizes the State of Ohio Board of Pharmacy to Adopt Emergency Rule to Ban the Sale and Use of Tianeptine" (PDF). State of Ohio Board of Pharmacy. 23 December 2022. Retrieved 5 January 2023.
  97. ^ Besher A, Friedlander EC. (PDF). Government of the State of Kentucky. Archived from the original (PDF) on 1 April 2023.
  98. ^ "Growing Danger Of 'Gas Station Heroin': Kentucky Latest State To Ban Tianeptine—Opioid-Like Drug Sold In Groceries". Forbes. Retrieved 26 October 2023.
  99. ^ "Adoption package for Emergency Rule 2ER23-1" (PDF). Florida Department of State.
  100. ^ "VIDEO: Attorney General Moody Outlaws Gas Station Heroin in Florida | My Florida Legal".
  101. ^ "Florida Just Banned 'Gas Station Heroin'". 25 September 2023.

External links edit

  • Tianeptine – David Pearce – The Good Drug Guide

January 01, 1970
tianeptine, sold, under, brand, names, stablon, tatinol, coaxil, among, others, atypical, tricyclic, antidepressant, which, used, mainly, treatment, major, depressive, disorder, although, also, used, treat, anxiety, asthma, irritable, bowel, syndrome, clinical. Tianeptine sold under the brand names Stablon Tatinol and Coaxil among others is an atypical tricyclic antidepressant which is used mainly in the treatment of major depressive disorder although it may also be used to treat anxiety asthma and irritable bowel syndrome 3 4 5 TianeptineClinical dataTrade namesStablon Coaxil TatinolOther namesTia 1 ZaZa 2 S 1574 3 4 5 JNJ 39823277 TPI 1062 6 AHFS Drugs comInternational Drug NamesRoutes ofadministrationBy mouthATC codeN06AX14 WHO Legal statusLegal statusBR Class C1 Other controlled substances 7 In general Rx onlyUS Investigational New Drug AU S4 8 Others controlled in FR BH SGPharmacokinetic dataBioavailability99 9 10 Protein binding95 10 MetabolismHepatic 10 by b oxidation 12 Elimination half life2 5 3 hours 9 10 4 9 hours elderly 10 11 ExcretionUrine 65 9 Feces 15 10 IdentifiersIUPAC name 7 3 Chloro 6 methyl 5 5 dioxo 11H benzo c 2 1 benzothiazepin 11 yl amino heptanoic acidCAS Number72797 41 2 Y 30123 17 2 sodium 1224690 84 9 sulfate 2231739 19 6 hemioxalate PubChem CID68870IUPHAR BPS7558ChemSpider62102 YUNII0T493YFU8OKEGGD02575 YChEBICHEBI 91749ChEMBLChEMBL1289110 NCompTox Dashboard EPA DTXSID7048295ECHA InfoCard100 131 750 100 069 844 100 131 750Chemical and physical dataFormulaC 21H 25Cl N 2O 4SMolar mass436 95 g mol 13D model JSmol Interactive imageSMILES Clc1cc2c cc1 C c3c N C S2 O O cccc3 NCCCCCCC O OInChI InChI 1S C21H24ClN2NaO4S c1 24 18 9 6 5 8 16 18 21 23 13 7 3 2 4 10 20 25 26 17 12 11 15 22 14 19 17 29 24 27 28 h5 6 8 9 11 12 14 21 23H 2 4 7 10 13H2 1H3 H 25 26 YKey JICJBGPOMZQUBB UHFFFAOYSA N Y N Y what is this verify Tianeptine has antidepressant and anxiolytic effects 13 with a relative lack of sedative anticholinergic and cardiovascular side effects 10 14 It has been found to act as an atypical agonist of the m opioid receptor with clinically negligible effects on the d and k opioid receptors 15 16 17 This may explain part of its antidepressant and anxiolytic effects however it is thought that tianeptine also modulates glutamate receptors and this may also explain tianeptine s antidepressant anxiolytic effects Tianeptine was discovered and patented by the French Society of Medical Research in the 1960s Currently tianeptine is approved in France and manufactured and marketed by Laboratories Servier SA it is also marketed in a number of other European countries under the trade name Coaxil as well as in Asia including Singapore and Latin America as Stablon and Tatinol but it is not available in Australia Canada New Zealand or the United Kingdom 18 19 In the US it is an unregulated drug sold under several names and some of these products have been found to be adulterated with other recreational drugs 20 Contents 1 Medical uses 1 1 Depression and anxiety 1 2 Other uses 2 Contraindications 3 Side effects 3 1 By frequency 4 Pharmacology 4 1 Pharmacodynamics 4 1 1 Atypical m opioid receptor agonist 4 1 2 Glutamatergic neurotrophic and neuroplastic modulation 4 1 3 Serotonin reuptake enhancer 4 1 4 Other actions 4 2 Pharmacokinetics 5 Chemistry 5 1 Analogues 6 Society and culture 6 1 Approval and brand names 6 2 Development 6 3 Recreational use 7 Legality 7 1 United States 8 See also 9 References 10 External linksMedical uses editDepression and anxiety edit Tianeptine shows efficacy against serious depressive episodes major depression comparable to amitriptyline imipramine and fluoxetine but with significantly fewer side effects 18 It was shown to be more effective than maprotiline in a group of people with co existing depression and anxiety 10 Tianeptine also displays significant anxiolytic properties and is useful in treating a spectrum of anxiety disorders including panic disorder as evidenced by a study in which those administered 35 CO2 gas carbogen on paroxetine or tianeptine therapy showed equivalent panic blocking effects 21 Like many antidepressants including bupropion the selective serotonin reuptake inhibitors the serotonin norepinephrine reuptake inhibitors moclobemide and numerous others it may also have a beneficial effect on cognition in people with depression induced cognitive dysfunction 22 A 2005 study in Egypt showed tianeptine to be effective in men with depression and erectile dysfunction 23 Tianeptine has been found to be effective in depression in people with Parkinson s disease 24 and with post traumatic stress disorder 25 for which it was as safe and effective as fluoxetine and moclobemide 26 Other uses edit A clinical trial comparing its efficacy and tolerability with amitriptyline in the treatment of irritable bowel syndrome showed that tianeptine was at least as effective as amitriptyline and produced fewer prominent adverse effects such as dry mouth and constipation 27 Tianeptine has been reported to be very effective for asthma In August 1998 Dr Fuad Lechin and colleagues at the Central University of Venezuela Institute of Experimental Medicine in Caracas published the results of a 52 week randomized controlled trial of asthmatic children the children in the groups who received tianeptine had a sharp decrease in clinical rating and increased lung function 28 Two years earlier they had found a close positive association between free serotonin in plasma and severity of asthma in symptomatic persons 28 As tianeptine was the only agent known to both reduce free serotonin in plasma and enhance uptake in platelets they decided to use it to see if reducing free serotonin levels in plasma would help 28 By November 2004 there had been two double blind placebo controlled crossover trials and an under 25 000 person open label study lasting over seven years both showing effectiveness 28 Tianeptine also has anticonvulsant and analgesic effects 29 and a clinical trial in Spain that ended in January 2007 has shown that tianeptine is effective in treating pain due to fibromyalgia 30 Tianeptine has been shown to have efficacy with minimal side effects in the treatment of attention deficit hyperactivity disorder 31 Contraindications editKnown contraindications include the following 32 Hypersensitivity to tianeptine or any of the tablet s excipients 33 Side effects editCompared to other tricyclic antidepressants it produces significantly fewer cardiovascular anticholinergic like dry mouth or constipation sedative and appetite stimulating effects 14 18 Unlike other tricyclic antidepressants tianeptine does not affect heart function 34 m Opioid receptor agonists can sometimes induce euphoria as does tianeptine occasionally at high doses well above the normal therapeutic range Tianeptine can also cause severe withdrawal symptoms after prolonged use at high doses which should prompt extreme caution 35 36 By frequency edit Sources 10 14 37 Common gt 1 frequency Headache up to 18 Dizziness up to 10 Insomnia nightmares up to 20 Drowsiness up to 10 Dry mouth up to 20 Constipation up to 15 Nausea Abdominal pain Weight gain 3 Agitation Anxiety irritability Uncommon 0 1 1 frequency Bitter taste Flatulence Gastralgia Blurred vision Muscle aches Premature ventricular contractions Micturition disturbances Palpitations Orthostatic hypotension Hot flushes Tremor Rare lt 0 1 frequency Hepatitis Hypomania 38 Euphoria ECG changes Pruritus allergic type skin reactions Protracted muscle aches General fatiguePharmacology editPharmacodynamics edit See also Pharmacology of antidepressants and Tricyclic antidepressant Binding profiles Tianeptine 39 Site Ki nM Species Ref MORTooltip m Opioid receptor 383 768 Ki 194 EC50Tooltip Half maximal effective concentration Human 15 39 15 DORTooltip d Opioid receptor gt 10 000 Ki 37 400 EC50 Human 15 39 15 KORTooltip k Opioid receptor gt 10 000 Ki 100 000 EC50 Human 15 39 15 SERTTooltip Serotonin transporter gt 10 000 Human 39 NETTooltip Norepinephrine transporter gt 10 000 Human 39 DATTooltip Dopamine transporter gt 10 000 Human 39 5 HT1A gt 10 000 Human 39 5 HT1B gt 10 000 Human 39 5 HT1D gt 10 000 Human 39 5 HT1E gt 10 000 Human 39 5 HT2A gt 10 000 Human 39 5 HT2B gt 10 000 Human 39 5 HT2C gt 10 000 Human 39 5 HT3 gt 10 000 Human 39 5 HT5A gt 10 000 Human 39 5 HT6 gt 10 000 Human 39 5 HT7 gt 10 000 Human 39 a1A gt 10 000 Human 39 a1B gt 10 000 Human 39 a2A gt 10 000 Human 39 a2B gt 10 000 Human 39 a2C gt 10 000 Human 39 b1 gt 10 000 Human 39 b2 gt 10 000 Human 39 D1 gt 10 000 Human 39 D2 gt 10 000 Human 39 D3 gt 10 000 Human 39 D4 gt 10 000 Human 39 D5 gt 10 000 Human 39 H1 gt 10 000 Human 39 H2 gt 10 000 Human 39 H3 gt 10 000 Human 39 H4 gt 10 000 Human 39 mAChTooltip Muscarinic acetylcholine receptor gt 10 000 Human 39 s1 gt 10 000 Guinea pig 39 s2 gt 10 000 Rat 39 I1 gt 10 000 Human 39 A1 gt 10 000 EC50 Human 15 VDCCTooltip Voltage dependent calcium channel gt 10 000 Human 39 Values are Ki nM unless otherwise noted The smaller the value the more strongly the drug interacts with the site Atypical m opioid receptor agonist edit In 2014 tianeptine was found to be a m opioid receptor MOR full agonist using human proteins 15 It was also found to act as a full agonist of the d opioid receptor DOR although with approximately 200 fold lower potency 15 The same researchers subsequently found that the MOR is required for the acute and chronic antidepressant like behavioral effects of tianeptine in mice and that its primary metabolite had similar activity as a MOR agonist but with a much longer elimination half life 40 Moreover in mice although tianeptine produced other opioid like behavioral effects such as analgesia and reward it did not result in tolerance or withdrawal 40 The authors suggested that tianeptine may be acting as a biased agonist of the MOR and that this may be responsible for its atypical profile as a MOR agonist 40 However there are reports that suggest that withdrawal effects resembling those of other typical opioid drugs including but not limited to depression insomnia and cold flu like symptoms do manifest following prolonged use at dosages far beyond the medical range 41 42 In addition to its therapeutic effects activation of the MOR is likely to also be responsible for the abuse potential of tianeptine at high doses that are well above the normal therapeutic range and efficacy threshold In rats when co administered with morphine tianeptine prevents morphine induced respiratory depression without impairing analgesia 43 In humans however tianeptine was found to increase respiratory depression when administered in conjunction with the potent opioid remifentanil 44 Glutamatergic neurotrophic and neuroplastic modulation edit Research suggests that tianeptine produces its antidepressant effects through indirect alteration and inhibition of glutamate receptor activity i e AMPA receptors and NMDA receptors and release of BDNFTooltip brain derived neurotrophic factor in turn affecting neural plasticity 45 46 47 48 14 18 Some researchers hypothesize that tianeptine has a protective effect against stress induced neuronal remodeling 45 14 There is also action on the NMDA and AMPA receptors 45 14 In animal models tianeptine inhibits the pathological stress induced changes in glutamatergic neurotransmission in the amygdala and hippocampus It may also facilitate signal transduction at the CA3 commissural associational synapse by altering the phosphorylation state of glutamate receptors With the discovery of the rapid and novel antidepressant effects of drugs such as ketamine many believe the efficacy of antidepressants is related to promotion of synaptic plasticity This may be achieved by regulating the excitatory amino acid systems that are responsible for changes in the strength of synaptic connections as well as enhancing BDNF expression although these findings are based largely on preclinical studies 18 Serotonin reuptake enhancer edit Tianeptine is no longer labelled a selective serotonin reuptake enhancer SSRE antidepressant 45 46 47 48 14 18 Tianeptine had been found to bind to the same allosteric site on the serotonin transporter SERT as conventional TCAs 49 However whereas conventional TCAs inhibit serotonin reuptake by the SERT tianeptine appeared to enhance it 49 This seems to be because of the unique C3 amino heptanoic acid side chain of tianeptine which in contrast to other TCAs is thought to lock the SERT in a conformation that increases affinity for and reuptake Vmax of serotonin 49 As such tianeptine was thought to act a positive allosteric modulator of the SERT or as a serotonin reuptake enhancer 49 Although tianeptine was originally found to have no effect in vitro on monoamine reuptake release or receptor binding upon acute and repeated administration tianeptine decreased the extracellular levels of serotonin in rat brain without a decrease in serotonin release leading to a theory of tianeptine enhancing serotonin reuptake 50 The enantiomer is more active in this sense than the enantiomer 51 However more recent studies found that long term administration of tianeptine does not elicit any marked alterations neither increases nor decreases in extracellular levels of serotonin in rats 45 However coadministration of tianeptine and the selective serotonin reuptake inhibitor fluoxetine inhibited the effect of tianeptine on long term potentiation in hippocampal CA1 area This is considered an argument for the opposite effects of tianeptine and fluoxetine on serotonin uptake 14 although it has been shown that fluoxetine can be partially substituted for tianeptine in animal studies 52 In any case the collective research suggests that direct modulation of the serotonin system is unlikely to be the mechanism of action underlying the antidepressant effects of tianeptine 49 Other actions edit Tianeptine modestly enhances the mesolimbic release of dopamine 53 and potentiates CNS D2 and D3 receptors 54 Tianeptine has no affinity for the dopamine transporter or the dopamine receptors 45 CREB TF CREB cAMP response element binding protein 55 is a cellular transcription factor It binds to certain DNA sequences called cAMP response elements CRE thereby increasing or decreasing the transcription of the genes 56 CREB has a well documented role in neuronal plasticity and long term memory formation in the brain Cocaine and amphetamine regulated transcript also known as CART is a neuropeptide protein that in humans is encoded by the CARTPT gene 57 58 CART appears to have roles in reward feeding stress 59 and it has the functional properties of an endogenous psychostimulant 60 Taking into account that CART production is upregulated by CREB 61 it could be hypothesized that due to tianeptine s central role in BDNF and neuronal plasticity this CREB may be the transcription cascade through which this drug enhances mesolimbic release of dopamine Research indicates possible anticonvulsant anti seizure and analgesic painkilling activity of tianeptine via downstream modulation of adenosine A1 receptors as the effects could be experimentally blocked by antagonists of this receptor 29 Tianpetine is also weak histone deacetylase inhibitor and analogs with increased potency and selectivity are developed 62 Pharmacokinetics edit The bioavailability of tianeptine is approximately 99 9 10 Its plasma protein binding is about 95 10 The metabolism of tianeptine is hepatic via b oxidation 10 CYP enzymes are not involved which limits the potential for drug drug interactions 10 Maximal concentration is reached in about an hour and the elimination half life is 2 5 to 3 hours 9 10 The elimination half life has been found to be increased to 4 to 9 hours in the elderly 11 Tianeptine is usually packaged as a sodium salt but can also be found as tianeptine sulfate a slower releasing formulation patented by Janssen in 2012 63 In 2022 Tonix Pharmaceuticals received permission from the US FDA to conduct phase II clinical trials on tianeptine hemioxalate extended release tablets designed for once daily use 64 The project was discontinued in late 2023 because of disappointing results in clinical trials Tianeptine has two active metabolites MC5 a pentanoic acid derivative of the parent compound and MC3 a propionic acid derivative 65 10 MC5 has a longer elimination half life 40 of approximately 7 6 hours and takes about a week to reach steady state concentration under daily dosing MC5 is a mu opioid agonist but not delta opioid agonist with EC50 at the mu opioid receptor of 0 545 mM vs 0 194 mM for tianeptine 40 MC3 is a very weak mu opioid agonist with an EC50 of 16 mM 40 Tianeptine is excreted 65 in the urine and 15 in feces 9 10 Chemistry editIn terms of chemical structure it is similar to tricyclic antidepressants TCAs but it has significantly different pharmacology and important structural differences so it is not usually grouped with them Analogues edit Although several related compounds are disclosed in the original patent 66 no activity data are provided and it was unclear whether these share tianeptine s unique pharmacological effects More recent structure activity relationship studies have since been conducted providing some further insight on m opioid d opioid and pharmacokinetic activity 67 68 69 70 71 Derivatives where the aromatic chlorine substituent is replaced by bromine iodine or methylthio and or the heptanoic acid tail is varied in length or replaced with other groups such as 3 methoxypropyl show similar or increased opioid receptor activity relative to tianeptine itself 72 73 74 Amineptine the most closely related drug to have been widely studied is a dopamine reuptake inhibitor with no significant effect on serotonin levels nor opioid agonist activity Tianeptinaline analog of tianeptine is a notable class I HDAC inhbitor 62 Society and culture edit nbsp Stablon box and blister pack Approval and brand names edit Brand names include Coaxil BG CR CZ EE HU LT LV PL RO RU SK UA Salymbra EE Stablon AR AT BR FR IN ID MY MX PK PT SG SK TH TT TR VE Tatinol CN Tianeurax DE Tynept IN Zinosal ES Tianesal PL Development edit Under the code names JNJ 39823277 and TPI 1062 tianeptine was previously under development for the treatment of major depressive disorder in the United States and Belgium 6 Phase I clinical trials were completed in Belgium and the United States in May and June 2009 respectively 6 For unclear reasons development of tianeptine was discontinued in both countries in January 2012 6 In October 2023 Tonix Pharmaceuticals announced that it had discontinued its development of tianeptine as a monotherapy for major depressive disorder after disappointing phase 2 clinical trial results 75 An ongoing clinical trial sponsored by the New York Psychiatric Institute is examining tianeptine s use in treatment resistant depression 76 U S National Poison Data System data on tianeptine showed a nationwide increase in tianeptine exposure calls and calls related to abuse and misuse during 2014 2017 17 Recreational use edit As a m opioid agonist tianeptine in large doses has high abuse potential In 2001 Singapore s Ministry of Health restricted tianeptine prescribing to psychiatrists due to its recreational potential 77 Between 1989 and 2004 in France 141 cases of recreational use were identified correlating to an incidence of 1 to 3 cases per 1000 persons treated with tianeptine and 45 between 2006 and 2011 According to Servier stopping of treatment with tianeptine is difficult due to the possibility of withdrawal symptoms in a person The severity of the withdrawal is dependent on the daily dose with high doses being extremely difficult to quit 78 better source needed 79 80 An official DEA statement 81 states that the withdrawal symptoms in humans typically result in agitation nausea vomiting tachycardia hypertension diarrhea tremor and diaphoresis similar to other opioid drugs In 2007 according to French Health Products Safety Agency tianeptine s manufacturer Servier agreed to modify the drug s label following problems with dependency 82 Tianeptine has been intravenously injected by drug users in Russia 83 84 This method of administration reportedly causes an opioid like effect and is sometimes used in an attempt to lessen opioid withdrawal symptoms 83 Tianeptine tablets contain silica and do not dissolve completely Often the solution is not filtered well thus particles in the injected fluid block capillaries leading to thrombosis and then severe necrosis Thus in Russia tianeptine sold under the brand name Coaxil is a schedule III controlled substance in the same list as the majority of benzodiazepines and barbiturates 85 The Centers for Disease Control and Prevention CDC has expressed concern that tianeptine may be an emerging public health risk citing an increase in exposure related calls to poison control centers in the United States 17 Sold retail as a dietary supplement and touted as a mood booster and an aid for concentration it is colloquially known as gas station heroin 86 In the US it is an unregulated drug sold under several product names and has been found to be adulterated with synthetic cannabinoid receptor agonists SCRAs or other drugs 20 A literature review conducted in 2018 found 25 articles involving 65 patients with tianeptine abuse or dependence 35 Limited data showed that a majority of patients were male and that age ranged from 19 to 67 Routes of intake included oral intravenous and insufflation entry In the 15 cases of overdose 8 combined ingestion with at least one other substance of which 3 resulted in death Six additional deaths are reported involving tianeptine making it 9 in total In this report the amount of tianeptine used ranged from 50 mg day to 10 g day orally Legality editIn 2003 Bahrain classified tianeptine a controlled substance due to increasing reports of misuse and recreational use 87 In Russia tianeptine sold under the brand name Coaxil is a schedule III controlled substance in the same list as the majority of benzodiazepines and barbiturates 85 On March 13 2020 with a decree approved by the Minister of Health Italy became the first European country to outlaw tianeptine considering it a Class I controlled substance 88 United States edit In the United States tianeptine is not considered by the Drug Enforcement Administration as a controlled substance or analogue thereof 89 However its use in dietary supplements and food is unlawful 90 The U S F D A has issued warnings as recently as January 2024 about the dangers of recreational tianeptine use and the risks posed by adulterated dietary supplements containing undeclared tianeptine 91 On 6 April 2018 Michigan became the first U S state to outlaw tianeptine sodium classifying it as a schedule II controlled substance 92 The scheduling of tianeptine sodium is effective 4 July 2018 93 On March 15 2021 Alabama outlawed tianeptine classifying it as a schedule II controlled substance 94 On July 1 2022 Tennessee outlawed tianeptine and adds any salt sulfate free acid or other preparation of tianeptine and any salt sulfate free acid compound derivative precursor or preparation thereof that is substantially chemically equivalent or identical with tianeptine classifying it as a schedule II controlled substance 95 On December 22 2022 Ohio outlawed tianeptine classifying it as a schedule I controlled substance with Ohio Governor Mike DeWine referencing the widespread availability of the chemical there as gas station heroin 96 On March 23 2023 Kentucky outlawed tianeptine classifying it as a schedule I substance by an order of the Governor of Kentucky 97 98 On September 20 2023 Florida outlawed tianeptine classifying it as a schedule I substance by an administrative edict issued by the Florida Attorney General 99 100 101 better source needed See also editAmineptine List of antidepressants List of investigational anxiolyticsReferences edit Uzbekov M 2011 FC13 09 Antidepressant tianeptine TIA action is based on the acceleration of serotonin turnover in the synapse a hypothesis European Psychiatry 26 1890 doi 10 1016 S0924 9338 11 73594 5 S2CID 143885547 Retrieved 3 December 2023 Wagner ML Pergolizzi J LeQuang JA Breve F Varrassi G June 2023 From Antidepressant Tianeptine to Street Drug ZaZa A Narrative Review Cureus 15 6 e40688 doi 10 7759 cureus 40688 PMC 10359047 PMID 37485121 a b Elks J 14 November 2014 The Dictionary of Drugs Chemical Data Chemical Data Structures and Bibliographies Springer pp 1195 ISBN 978 1 4757 2085 3 a b Index Nominum 2000 International Drug Directory Taylor amp Francis 2000 pp 1024 ISBN 978 3 88763 075 1 a b Tianeptine International database Drugs com a b c d Tianeptine AdisInsight AdisInsight Springer Retrieved 31 January 2016 Anvisa 31 March 2023 RDC Nº 784 Listas de Substancias Entorpecentes Psicotropicas Precursoras e Outras sob Controle Especial Collegiate Board Resolution No 784 Lists of Narcotic Psychotropic Precursor and Other Substances under Special Control in Brazilian Portuguese Diario Oficial da Uniao published 4 April 2023 Archived from the original on 3 August 2023 Retrieved 16 August 2023 Poisons Standard June 2017 29 May 2017 a b c d e f Royer RJ Albin H Barrucand D Salvadori Failler C Kamoun A 1988 Pharmacokinetic and metabolic parameters of tianeptine in healthy volunteers and in populations with risk factors Clinical Neuropharmacology 11 Suppl 2 S90 6 PMID 3180120 a b c d e f g h i j k l m n o p Wagstaff AJ Ormrod D Spencer CM March 2001 Tianeptine a review of its use in depressive disorders CNS Drugs 15 3 231 59 doi 10 2165 00023210 200115030 00006 PMID 11463130 S2CID 37796160 a b Carlhant D Le Garrec J Guedes Y Salvadori C Mottier D Riche C September 1990 Pharmacokinetics and bioavailability of tianeptine in the elderly Drug Investigation 2 3 167 172 doi 10 1007 BF03259191 S2CID 56502717 Fromenty B Freneaux E Labbe G Deschamps D Larrey D Letteron P et al 1 November 1989 Tianeptine a new tricyclic antidepressant metabolized by beta oxidation of its heptanoic side chain inhibits the mitochondrial oxidation of medium and short chain fatty acids in mice Biochem Pharmacol 38 21 3743 3751 doi 10 1016 0006 2952 89 90580 7 PMID 2597170 Defrance R Marey C Kamoun A 1988 Antidepressant and anxiolytic activities of tianeptine an overview of clinical trials PDF Clinical Neuropharmacology 11 Suppl 2 S74 82 PMID 2902922 Archived from the original PDF on 4 April 2016 a b c d e f g h Kasper S McEwen BS 2008 Neurobiological and clinical effects of the antidepressant tianeptine CNS Drugs 22 1 15 26 doi 10 2165 00023210 200822010 00002 PMID 18072812 S2CID 30330824 a b c d e f g h i j Gassaway MM Rives ML Kruegel AC Javitch JA Sames D July 2014 The atypical antidepressant and neurorestorative agent tianeptine is a m opioid receptor agonist Translational Psychiatry 4 7 e411 doi 10 1038 tp 2014 30 PMC 4119213 PMID 25026323 Berridge KC Kringelbach ML August 2008 Affective neuroscience of pleasure reward in humans and animals Psychopharmacology 199 3 457 80 doi 10 1007 s00213 008 1099 6 PMC 3004012 PMID 18311558 a b c El Zahran T Schier J Glidden E Kieszak S Law R Bottei E et al August 2018 Characteristics of Tianeptine Exposures Reported to the National Poison Data System United States 2000 2017 MMWR Morbidity and Mortality Weekly Report 67 30 815 818 doi 10 15585 mmwr mm6730a2 PMC 6072055 PMID 30070980 a b c d e f Akiki T The etiology of depression and the therapeutic implications Glob J Med Res 13 6 ISSN 2249 4618 Archived from the original on 3 November 2016 Retrieved 26 August 2015 Tianeptine Sodium Martindale The Complete Drug Reference London UK Pharmaceutical Press 5 December 2011 Retrieved 2 December 2013 a b Counts CJ Spadaro AV Cerbini TA Krotulski AJ Greller HA Nelson LS et al February 2024 Notes from the Field Cluster of Severe Illness from Neptune s Fix Tianeptine Linked to Synthetic Cannabinoids New Jersey June November 2023 MMWR Morbidity and Mortality Weekly Report 73 4 89 90 doi 10 15585 mmwr mm7304a5 PMC 10843069 PMID 38300852 Schruers K Griez E December 2004 The effects of tianeptine or paroxetine on 35 CO2 provoked panic in panic disorder Journal of Psychopharmacology 18 4 553 8 doi 10 1177 0269881104047283 PMID 15582922 S2CID 26981110 Baune BT Renger L September 2014 Pharmacological and non pharmacological interventions to improve cognitive dysfunction and functional ability in clinical depression a systematic review Psychiatry Research 219 1 25 50 doi 10 1016 j psychres 2014 05 013 PMID 24863864 S2CID 23684657 El Shafey H Atteya A Abu El Magd S Hassanein A Fathy A Shamloul R September 2006 Tianeptine can be effective in men with depression and erectile dysfunction The Journal of Sexual Medicine 3 5 910 917 doi 10 1111 j 1743 6109 2005 00141 x PMID 16942535 Levin OS May 2007 Coaxil tianeptine in the treatment of depression in Parkinson s disease Neuroscience and Behavioral Physiology 37 4 419 24 doi 10 1007 s11055 007 0029 0 PMID 17457538 S2CID 7637174 Aleksandrovskiĭ I Avedisova AS Boev IV Bukhanovkskiĭ AO Voloshin VM Tsygankov BD et al 2005 Efficacy and tolerability of coaxil tianeptine in the therapy of posttraumatic stress disorder Effektivnost i perenosimost koaksila tianeptina pri terapii posttravmaticheskogo stressovogo rasstrojstva Efficacy and tolerability of coaxil tianeptine in the therapy of posttraumatic stress disorder Zhurnal Nevrologii I Psikhiatrii Imeni S S Korsakova in Russian 105 11 24 9 PMID 16329631 Onder E Tural U Aker T April 2006 A comparative study of fluoxetine moclobemide and tianeptine in the treatment of posttraumatic stress disorder following an earthquake European Psychiatry 21 3 174 9 doi 10 1016 j eurpsy 2005 03 007 PMID 15964747 S2CID 21322928 Sohn W Lee OY Kwon JG Park KS Lim YJ Kim TH et al September 2012 Tianeptine vs amitriptyline for the treatment of irritable bowel syndrome with diarrhea a multicenter open label non inferiority randomized controlled study Neurogastroenterology and Motility 24 9 860 e398 doi 10 1111 j 1365 2982 2012 01945 x PMID 22679908 S2CID 2914428 a b c d Lechin F van der Dijs B Lechin AE November 2004 Treatment of bronchial asthma with tianeptine Methods and Findings in Experimental and Clinical Pharmacology 26 9 697 701 doi 10 1358 mf 2004 26 9 872567 PMID 15632955 a b Uzbay TI May 2008 Tianeptine potential influences on neuroplasticity and novel pharmacological effects Progress in Neuro Psychopharmacology amp Biological Psychiatry 32 4 915 24 doi 10 1016 j pnpbp 2007 08 007 PMID 17826881 S2CID 22365299 ISRCTN16400909 Tianeptine for the treatment of fibromyalgia a prospective double blind randomised single centre placebo controlled parallel group study Controlled trials com Archived from the original on 21 July 2010 Retrieved 13 August 2010 Niederhofer H 2004 Tianeptine as a slightly effective therapeutic option for attention deficit hyperactivity disorder Neuropsychobiology 49 3 130 3 doi 10 1159 000076721 PMID 15034228 S2CID 34300575 Package Insert Stablon German PDF Servier Austria GmbH 20 August 2012 Archived from the original PDF on 11 August 2016 Retrieved 24 February 2020 Le Bricquir Y Larrey D Blanc P Pageaux GP Michel H November 1994 Tianeptine an instance of drug induced hepatotoxicity predicted by prospective experimental studies Journal of Hepatology 21 5 771 773 doi 10 1016 s0168 8278 94 80237 8 PMID 7890892 Bril A Abadie C Ben Baouali A Maupoil V Rochette L 1993 Absence of relationship between antiarrhythmic effects of antidepressant drugs and lipid peroxidation Pharmacology 46 1 23 32 doi 10 1159 000139025 PMID 8434029 a b Lauhan R Hsu A Alam A Beizai K November 2018 Tianeptine Abuse and Dependence Case Report and Literature Review Psychosomatics 59 6 547 553 doi 10 1016 j psym 2018 07 006 PMID 30149933 S2CID 52099752 Vadachkoria D Gabunia L Gambashidze K Pkhaladze N Kuridze N September 2009 Addictive potential of Tianeptine the threatening reality Georgian Medical News 174 92 4 PMID 19801742 Waintraub L Septien L Azoulay P January 2002 Efficacy and safety of tianeptine in major depression evidence from a 3 month controlled clinical trial versus paroxetine CNS Drugs 16 1 65 75 doi 10 2165 00023210 200216010 00005 PMID 11772119 S2CID 31125177 Gulen Yildirim S Basterzi AD Goka E 2004 Tianeptinin Neden Oldugu Hipomani Bir Olgu Sunumu Tianeptine Induced Mania A Case Report PDF Klinik Psikiyatri Dergisi in Turkish 7 4 177 180 Archived from the original PDF on 30 June 2006 a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am Roth BL Driscol J PDSP Ki Database Psychoactive Drug Screening Program PDSP University of North Carolina at Chapel Hill and the United States National Institute of Mental Health Retrieved 14 August 2017 a b c d e f Samuels BA Nautiyal KM Kruegel AC Levinstein MR Magalong VM Gassaway MM et al September 2017 The Behavioral Effects of the Antidepressant Tianeptine Require the Mu Opioid Receptor Neuropsychopharmacology 42 10 2052 2063 doi 10 1038 npp 2017 60 PMC 5561344 PMID 28303899 Springer J Cubala WJ March 2018 Tianeptine Abuse and Dependence in Psychiatric Patients A Review of 18 Case Reports in the Literature Journal of Psychoactive Drugs 50 3 275 280 doi 10 1080 02791072 2018 1438687 PMID 29494783 S2CID 3603781 Marraffa JM Stork CM Hoffman RS Su MK November 2018 Poison control center experience with tianeptine an unregulated pharmaceutical product with potential for abuse Clinical Toxicology 56 11 1155 1158 doi 10 1080 15563650 2018 1476694 PMID 29799284 S2CID 44112801 Cavalla D Chianelli F Korsak A Hosford PS Gourine AV Marina N August 2015 Tianeptine prevents respiratory depression without affecting analgesic effect of opiates in conscious rats European Journal of Pharmacology 761 268 72 doi 10 1016 j ejphar 2015 05 067 PMID 26068549 Algera H van der Schrier R Cavalla D van Velzen M Roozekrans M McMorn A et al October 2022 Respiratory Effects of the Atypical Tricyclic Antidepressant Tianeptine in Human Models of Opioid induced Respiratory Depression Anesthesiology 137 4 446 458 doi 10 1097 ALN 0000000000004324 PMID 35867853 S2CID 250989511 a b c d e f McEwen BS Chattarji S Diamond DM Jay TM Reagan LP Svenningsson P et al March 2010 The neurobiological properties of tianeptine Stablon from monoamine hypothesis to glutamatergic modulation Molecular Psychiatry 15 3 237 49 doi 10 1038 mp 2009 80 PMC 2902200 PMID 19704408 a b McEwen BS Chattarji S December 2004 Molecular mechanisms of neuroplasticity and pharmacological implications the example of tianeptine European Neuropsychopharmacology 14 Suppl 5 S497 502 doi 10 1016 j euroneuro 2004 09 008 PMID 15550348 S2CID 21953270 a b McEwen BS Olie JP June 2005 Neurobiology of mood anxiety and emotions as revealed by studies of a unique antidepressant tianeptine Molecular Psychiatry 10 6 525 37 doi 10 1038 sj mp 4001648 PMID 15753957 a b Brink CB Harvey BH Brand L January 2006 Tianeptine a novel atypical antidepressant that may provide new insights into the biomolecular basis of depression Recent Patents on CNS Drug Discovery 1 1 29 41 doi 10 2174 157488906775245327 PMID 18221189 Archived from the original on 14 April 2013 a b c d e Bailey SJ Almatroudi A Kouris A 2018 Tianeptine An Atypical Antidepressant with Multimodal Pharmacology PDF Current Psychopharmacology 6 2 doi 10 2174 2211556006666170525154616 ISSN 2211 5560 S2CID 55965184 Mennini T Mocaer E Garattini S November 1987 Tianeptine a selective enhancer of serotonin uptake in rat brain Naunyn Schmiedeberg s Archives of Pharmacology 336 5 478 82 doi 10 1007 bf00169302 PMID 3437921 S2CID 21499462 Oluyomi AO Datla KP Curzon G March 1997 Effects of the and enantiomers of the antidepressant drug tianeptine on 5 HTP induced behaviour Neuropharmacology 36 3 383 7 doi 10 1016 s0028 3908 97 00016 6 PMID 9175617 S2CID 11465294 Alici T Kayir H Aygoren MO Saglam E Uzbay IT January 2006 Discriminative stimulus properties of tianeptine Psychopharmacology 183 4 446 51 doi 10 1007 s00213 005 0210 5 PMID 16292591 S2CID 5820336 Invernizzi R Pozzi L Garattini S Samanin R March 1992 Tianeptine increases the extracellular concentrations of dopamine in the nucleus accumbens by a serotonin independent mechanism Neuropharmacology 31 3 221 7 doi 10 1016 0028 3908 92 90171 K PMID 1630590 S2CID 21610131 Dziedzicka Wasylewska M Rogoz Z Skuza G Dlaboga D Maj J March 2002 Effect of repeated treatment with tianeptine and fluoxetine on central dopamine D 2 D 3 receptors Behavioural Pharmacology 13 2 127 38 doi 10 1097 00008877 200203000 00004 PMID 11981225 S2CID 2126834 Bourtchuladze R Frenguelli B Blendy J Cioffi D Schutz G Silva AJ October 1994 Deficient long term memory in mice with a targeted mutation of the cAMP responsive element binding protein Cell 79 1 59 68 doi 10 1016 0092 8674 94 90400 6 PMID 7923378 S2CID 17250247 Purves D Augustine GJ Fitzpatrick D Hall WC LaMantia AS McNamara JO et al 2008 Neuroscience 4th ed Sinauer Associates pp 170 6 ISBN 978 0 87893 697 7 Douglass J Daoud S March 1996 Characterization of the human cDNA and genomic DNA encoding CART a cocaine and amphetamine regulated transcript Gene 169 2 241 5 doi 10 1016 0378 1119 96 88651 3 PMID 8647455 Kristensen P Judge ME Thim L Ribel U Christjansen KN Wulff BS et al May 1998 Hypothalamic CART is a new anorectic peptide regulated by leptin Nature 393 6680 72 6 Bibcode 1998Natur 393 72K doi 10 1038 29993 PMID 9590691 S2CID 4427258 Zhang M Han L Xu Y June 2012 Roles of cocaine and amphetamine regulated transcript in the central nervous system Clinical and Experimental Pharmacology amp Physiology 39 6 586 92 doi 10 1111 j 1440 1681 2011 05642 x PMID 22077697 S2CID 25134612 Kuhar MJ Adams S Dominguez G Jaworski J Balkan B February 2002 CART peptides Neuropeptides 36 1 1 8 doi 10 1054 npep 2002 0887 PMID 12147208 S2CID 7079530 Rogge GA Jones DC Green T Nestler E Kuhar MJ January 2009 Regulation of CART peptide expression by CREB in the rat nucleus accumbens in vivo Brain Research 1251 42 52 doi 10 1016 j brainres 2008 11 011 PMC 2734444 PMID 19046951 a b Zhao WN Ghosh B Tyler M Lalonde J Joseph NF Kosaric N et al September 2018 Class I Histone Deacetylase Inhibition by Tianeptinaline Modulates Neuroplasticity and Enhances Memory ACS Chemical Neuroscience 9 9 2262 2273 doi 10 1021 acschemneuro 8b00116 hdl 1721 1 126372 PMID 29932631 S2CID 49389560 Tianeptine sulfate salt forms and methods of making and using the same Tonix Pharmaceuticals Announces IND Clearance for TNX 601 ER as a Potential Treatment for Major Depressive Disorder Tonix Pharmaceuticals Holding Corp GlobeNewswire News Room 3 October 2022 Retrieved 5 November 2022 Szafarz M Wencel A Pociecha K Fedak FA Wlaz P Wyska E February 2018 Pharmacokinetic study of tianeptine and its active metabolite MC5 in rats following different routes of administration using a novel liquid chromatography tandem mass spectrometry analytical method Naunyn Schmiedeberg s Archives of Pharmacology 391 2 185 196 doi 10 1007 s00210 017 1448 2 PMC 5778159 PMID 29230490 S2CID 253742631 FR 2104728 Malen C Danree B Poignant JC Nouveaux derives tricycliques et leur procede de preparation Novel tricyclic derivatives and process for preparing the same published 1972 04 21 assigned to Science Union et CIE Societe Francaise de Recherche Medicale Kruegel AC 2015 Chemical and Biological Explorations of Novel Opioid Receptor Modulators Thesis Columbia University p 338 358 doi 10 7916 d8v1242f Labrid C Moleyre J Poignant JC Malen C Mocaer E Kamoun A 1988 Structure activity relationships of tricyclic antidepressants with special reference to tianeptine Clinical Neuropharmacology 11 Suppl 2 S21 S31 PMID 3180115 Sanchez Mateo CC Darias V Exposito Orta MA Albertos LM January 2003 Neuropharmacological study of hetero 2 1 benzothiazepine derivatives analogues of tianeptine Farmaco 58 1 Societa Chimica Italiana 1 10 doi 10 1016 S0014 827X 02 00021 6 PMID 12595031 Sanchez Mateo CC Darias V Albertos LM Exposito Orta MA 2003 Psychopharmacological effects of tianeptine analogous hetero 2 1 benzothiazepine derivatives Arzneimittel Forschung 53 1 12 20 doi 10 1055 s 0031 1297064 PMID 12608009 S2CID 23593291 Exposito Orta MA Albertos LM Darias V Sanchez Mateo CC 2004 Behavioural effects of thieno and pyrazolo 2 1 benzothiazepine derivatives in mice Arzneimittel Forschung 54 7 365 70 doi 10 1055 s 0031 1296985 PMID 15344839 S2CID 24437547 Kruegel AC 2015 Chemical and Biological Explorations of Novel Opioid Receptor Modulators PhD thesis Columbia University doi 10 7916 D8V1242F US 10183919 Kruegel AC Henke A Gassaway MM Rives MM Javitch JA Sames D Class of mu opioid receptor agonists published 2019 01 22 assigned to The Trustees of Columbia University in the City of New York WO 2017049158 Kruegel A Sames D Gassaway M Javitch JA Carboxylic diarylthiazepineamines as mu opioid receptor agonists published 2017 03 23 assigned to The Trustees of Columbia University in the City of New York Tonix Pharmaceuticals Announces Topline Results from Phase 2 Proof of Concept Study of TNX 601 ER for the Treatment of Major Depressive Disorder Tonix Pharmaceuticals Holding Corp 31 October 2023 Retrieved 2 November 2023 Javitch JA 15 June 2023 Tianeptine for Treatment Resistant Depression Clinicaltrials gov Retrieved 2 November 2023 World Health Organization 2001 Pharmaceuticals Restrictions in use and availability March 2001 PDF Archived from the original PDF on 17 November 2008 Retrieved 24 July 2008 APM Health Europe 2007 Addiction leads to warning on Servier s antidepressant Stablon Archived from the original on 7 July 2011 Retrieved 24 July 2008 Gibaja V 2006 Use Drug Abuse and Tianeptine in French PDF Archived from the original PDF on 20 July 2011 Retrieved 24 July 2008 Tianeptine Stablon dans la depression risque trop important de dependance www prescrire org Drug Enforcement AdministrationDiversion Control DivisionDrug amp Chemical Evaluation Section Tianeptine PDF French Health Products Safety Agency Afssaps 2007 Important Information on Drug Update of the Summary of Product Characteristics Stablon 16 May 2007 French Archived from the original on 1 April 2008 Retrieved 24 July 2008 a b Ives R 2008 Assessment Mission Report for the SCAD V Programme Component on Prevention and on Media Work PDF Archived from the original PDF on 1 December 2010 Retrieved 4 November 2008 Illicit Drug Trades in the Russian Federation PDF United Nations Office on Drugs and Crime April 2008 Retrieved 16 July 2014 a b Decision of the Government of the Russian Federation No 681 of June 30 1998 on the Approval of the List of Narcotic Drugs Psychotropic Substances and Their Precursors That Shall Be Subject to Control in the Russian Federation with Amendments and Additions in Russian Hoffman J 10 January 2024 Gas Station Heroin Sold as Dietary Supplement Alarms Health Officials The New York Times via NYTimes com World Health Organization 2003 Pharmaceuticals Restrictions in use and availability April 2003 PDF Archived from the original PDF on 29 June 2011 Retrieved 24 July 2008 Gazzetta Ufficiale Tianeptine PDF Office of Diversion Control at the D E A Retrieved 25 May 2023 Tianeptine in Dietary Supplements Food and Drug Administration 22 February 2023 Retrieved 25 May 2023 Musa A 24 January 2024 FDA urges consumers not to buy tianeptine products due to serious risks as lawmakers call for immediate action CNN Retrieved 30 January 2024 Michigan approves ban on antidepressant tianeptine sodium Associated Press via Detroit Free Press Public Health Code Section 333 7214 amended Michigan Legislature Legislative Council State of Michigan Retrieved 18 May 2018 permanent dead link New crime trend in Giles Co after Alabama stops selling ZaZa Red controversial stimulant WKRN News 2 25 May 2021 Retrieved 14 December 2022 HB 2043 by Cochran Controlled Substances Tennessee General Assembly 30 March 2022 Archived from the original on 8 April 2022 Governor DeWine Authorizes the State of Ohio Board of Pharmacy to Adopt Emergency Rule to Ban the Sale and Use of Tianeptine PDF State of Ohio Board of Pharmacy 23 December 2022 Retrieved 5 January 2023 Besher A Friedlander EC Statement of Emergency PDF Government of the State of Kentucky Archived from the original PDF on 1 April 2023 Growing Danger Of Gas Station Heroin Kentucky Latest State To Ban Tianeptine Opioid Like Drug Sold In Groceries Forbes Retrieved 26 October 2023 Adoption package for Emergency Rule 2ER23 1 PDF Florida Department of State VIDEO Attorney General Moody Outlaws Gas Station Heroin in Florida My Florida Legal Florida Just Banned Gas Station Heroin 25 September 2023 External links editTianeptine David Pearce The Good Drug Guide Retrieved from https en wikipedia org w index php title Tianeptine amp oldid 1222899971, wikipedia, wiki, book, books, library,

article

, read, download, free, free download, mp3, video, mp4, 3gp, jpg, jpeg, gif, png, picture, music, song, movie, book, game, games.