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Amineptine

April 11, 2024

Amineptine, formerly sold under the brand name Survector among others, is an atypical antidepressant of the tricyclic antidepressant (TCA) family.[4][5] It acts as a selective and mixed dopamine reuptake inhibitor and releasing agent, and to a lesser extent as a norepinephrine reuptake inhibitor.[4][5]

Amineptine
Clinical data
Trade namesSurvector, others
Other namesS-1694
Routes of
administration		Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
MetabolismHepatic
Elimination half-lifeAmineptine: 0.8–1.0 hours[2][3]
Metabolite: 1.5–2.5 hours[2][3]
ExcretionRenal
Identifiers
  • 7-[(10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5-yl)amino]heptanoic acid
CAS Number
  • 57574-09-1 Y
PubChem CID
  • 34870
DrugBank
  • DB04836 Y
ChemSpider
  • 32091 Y
UNII
  • 27T1I13L6G
KEGG
  • D07335 Y
ChEBI
  • CHEBI:32499 Y
ChEMBL
  • ChEMBL418995 Y
CompTox Dashboard (EPA)
  • DTXSID1048831
ECHA InfoCard100.055.271
Chemical and physical data
FormulaC22H28NO2
Molar mass338.471 g·mol−1
3D model (JSmol)
  • Interactive image
  • O=C(O)CCCCCCNC1c2ccccc2CCc2ccccc21
  • InChI=1S/C22H27NO2/c24-21(25)13-3-1-2-8-16-23-22-19-11-6-4-9-17(19)14-15-18-10-5-7-12-20(18)22/h4-7,9-12,22-23H,1-3,8,13-16H2,(H,24,25) Y
  • Key:ONNOFKFOZAJDHT-UHFFFAOYSA-N Y
  (verify)

Amineptine was developed by the French Society of Medical research in the 1960s.[6] Introduced in France in 1978 by the pharmaceutical company Servier,[7] amineptine soon gained a reputation for abuse due to its short-lived, but pleasant, stimulant effect experienced by some patients.

After its release into the European market, cases of hepatotoxicity emerged, some serious. This, along with the potential for abuse, led to the suspension of the French marketing authorization for Survector in 1999.[8]

Amineptine is illegal in both Germany and the United States.

Medical uses edit

Amineptine was approved in France for severe clinical depression of endogenous origin in 1978.[9]

Contraindications edit

Precautions for use edit

Warnings and precautions before taking amineptine:[10]

Effects on the fetus edit

  • Lacking information in humans
  • Non-teratogenic in rodents

Side effects edit

Dermatological edit

Severe acne due to amineptine was first reported in 1988 by various authors—Grupper, Thioly-Bensoussan, Vexiau, Fiet, Puissant, Gourmel, Teillac, Levigne, to name a few—simultaneously[11][12][13][14][15] in the same issue of Annales de Dermatologie et de Vénéréologie and in the 12 March 1988 issue of The Lancet.[16] A year later, Dr Martin-Ortega and colleagues in Barcelona, Spain reported a case of "acneiform eruption" in a 54-year-old woman whose intake of amineptine was described as "excessive."[17] One year after that, Vexiau and colleagues reported six women, one of whom never admitted to using amineptine, getting severe acne concentrated in the face, back and thorax, the severity of which varied with the dosage.[18] Most of them were treated unsuccessfully with isotretinoin (Accutane) for about 18 months; two of the three that discontinued amineptine experienced a reduction in cutaneous symptoms, with the least affected patient going into remission.[18]

Psychiatric edit

Psychomotor excitation can very rarely occur with this drug.

Abuse and dependence edit

The risk of addiction is low, but exists nonetheless. Between 1978 and 1988, there were 186 cases of amineptine addiction reported to the French Regional Centres of Pharmacovigilance; an analysis of 155 of those cases found that they were predominantly female, and that two-thirds of cases had known risk factors for addiction.[19] However, a 1981 study of known opiate addicts and schizophrenia patients found no drug addiction in any of the subjects.[20] In a 1990 study of eight amineptine dependence cases, the gradual withdrawal of amineptine could be achieved without problems in six people; in two others, anxiety, psychomotor agitation, and/or bulimia appeared.[21]

Withdrawal edit

Pharmacodependence is very common with amineptine compared to other antidepressants.[22] A variety of psychological symptoms can occur during withdrawal from amineptine,[23] such as anxiety and agitation.[24]

Cardiovascular edit

Very rarely:

Hepatic edit

Amineptine can rarely cause hepatitis, of the cytolytic, cholestatic varieties.[25] Amineptine-induced hepatitis, which is sometimes preceded by a rash, is believed to be due to an immunoallergic reaction.[26] It resolves upon discontinuation of the offending drug.[25] The risk of getting this may or may not be genetically determined.[27]

Additionally, amineptine is known to rarely elevate transaminases, alkaline phosphatase, and bilirubin.[28]

Mixed hepatitis, which is very rare, generally occurs between the 15th and 30th day of treatment. Often preceded by sometimes intense abdominal pains, nausea, vomiting or a rash, the jaundice is variable. Hepatitis is either of mixed type or with cholestatic prevalence. The evolution was, in all the cases, favorable to the discontinuation of the drug. The mechanism is discussed (immunoallergic and/or toxic).[29]

In circa 1994 Spain, there was a case associating acute pancreatitis and mixed hepatitis, after three weeks of treatment.[30]

Lazaros and colleagues at the Western Attica General Hospital in Athens, Greece reported two cases of drug induced hepatitis 18 and 15 days of treatment.[31]

One case of cytolytic hepatitis occurred after ingestion of only one tablet.[32]

Gastrointestinal edit

  • Acute pancreatitis (very rare) A case associating acute pancreatitis and mixed hepatitis after three weeks of treatment.[30]

Immunological edit

In 1989, Sgro and colleagues at the Centre de Pharmacovigilance[33] in Dijon reported a case of anaphylactic shock in a woman who had been taking amineptine.[34]

Pharmacology edit

Pharmacodynamics edit

Amineptine[35]
Site Ki (nM) Species Ref
SERTTooltip Serotonin transporter >100,000 (IC50) Rat [36]
NETTooltip Norepinephrine transporter 10,000 (IC50)
3,560		 Rat
Canine		 [36][37]
[38]
DATTooltip Dopamine transporter 1,000–1,400 (IC50)
3,330		 Rat
Canine		 [36][39][37]
[38]
5-HT1A >100,000 Rat [40]
5-HT2A 74,000 Rat [40]
α1 >100,000 Rat [40]
α2 >100,000 Rat [40]
β >100,000 Rat [40]
D1 >100,000 Canine [36]
D2 >100,000 Rat/canine [36][40]
H1 >100,000
13,000		 Rat
Guinea pig		 [40]
[41]
mAChTooltip Muscarinic acetylcholine receptor >100,000 Rat [40]
Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site.

Amineptine inhibits the reuptake of dopamine and, to a much lesser extent, of norepinephrine.[37][36][42] In addition, it has been found to induce the release of dopamine.[37][36][42] However, amineptine is much less efficacious as a dopamine releasing agent relative to D-amphetamine, and the drug appears to act predominantly as a dopamine reuptake inhibitor.[37][36][42] In contrast to the case for dopamine, amineptine does not induce the release of norepinephrine, and hence acts purely as a norepinephrine reuptake inhibitor.[37][36][42] Unlike other TCAs, amineptine interacts very weakly or not at all with the serotonin, adrenergic, dopamine, histamine, and muscarinic acetylcholine receptors.[40][41][42] The major metabolites of amineptine have similar activity to that of the parent compound, albeit with lower potency.[42]

No human data appear to be available for binding or inhibition of the monoamine transporters by amineptine.[43]

Pharmacokinetics edit

Peak plasma levels of amineptine following a single 100 mg oral dose have been found to range between 277 and 2,215 ng/mL (818–6,544 nM), with a mean of 772 ng/mL (2,281 nM), whereas maximal plasma concentrations of its major metabolite ranged between 144 and 1,068 ng/mL (465–3,452 nM), with a mean of 471 ng/mL (1,522 nM).[2] After a single 200 mg oral dose of amineptine, mean peak plasma levels of amineptine were around 750 to 940 ng/mL (2,216–2,777 nM), while those of its major metabolite were about 750 to 970 ng/mL (2,216–3,135 nM).[3] The time to peak concentrations is about 1 hour for amineptine and 1.5 hours for its major metabolite.[2][3] The elimination half-life of amineptine is about 0.80 to 1.0 hours and that of its major metabolite is about 1.5 to 2.5 hours.[2][3] Due to their very short elimination half-lives, amineptine and its major metabolite do not accumulate significantly with repeated administration.[2]

Society and culture edit

Brand names edit

Amineptine has been sold under a variety of brand names including Survector, Maneon, Directim, Neolior, Provector, and Viaspera.

Legal status edit

It had been proposed that Amineptine become a Schedule I controlled substance in the United States in July 2021.[44] This announcement was followed by the placement of Amineptine into Schedule I. [45]

References edit

  1. ^ 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.
  2. ^ a b c d e f Lachatre G, Piva C, Riche C, et al. (1989). "Single-dose pharmacokinetics of amineptine and of its main metabolite in healthy young adults". Fundam Clin Pharmacol. 3 (1): 19–26. doi:10.1111/j.1472-8206.1989.tb00026.x. PMID 2714729. S2CID 25992333.
  3. ^ a b c d e Sbarra C, Castelli MG, Noseda A, Fanelli R (1981). "Pharmacokinetics of amineptine in man". Eur J Drug Metab Pharmacokinet. 6 (2): 123–6. doi:10.1007/bf03189478. PMID 7274306. S2CID 31069503.
  4. ^ a b Vaugeois JM, Corera AT, Deslandes A, Costentin J (June 1999). "Although chemically related to amineptine, the antidepressant tianeptine is not a dopamine uptake inhibitor". Pharmacology Biochemistry and Behavior. 63 (2): 285–90. doi:10.1016/S0091-3057(98)00242-1. PMID 10371658. S2CID 32862145.
  5. ^ a b Dunlop BW, Nemeroff CB (2007). "The role of dopamine in the pathophysiology of depression". Arch. Gen. Psychiatry. 64 (3): 327–37. doi:10.1001/archpsyc.64.3.327. PMID 17339521. S2CID 26550661.
  6. ^ DE Patent 2011806 – NEW TRICYCLIC DERIVATIVES AND PROCESS FOR THEIR MANUFACTURE
  7. ^ Sittig M (1 April 1988) [1979]. Pharmaceutical Manufacturing Encyclopedia (2nd ed.). Park Ridge, New Jersey, United States American: William Andrew Publishing/Noyes Publications. ISBN 978-0-8155-1144-1. from the original on 23 October 2005. Retrieved 29 October 2005.[page needed]
  8. ^ "Docket No. 02N-0101". U.S. Food and Drug Administration. 9 April 2002. Retrieved 30 January 2014.
  9. ^ Doctissimo (2005). (in French). Archived from the original on 9 March 2005. Retrieved 27 October 2005.
  10. ^ Amineptine Medication – Uses, Side Effects and Precautions of Amineptine. Health-care-information.org. Retrieved on 28 September 2013
  11. ^ Grupper C (1988). "[New iatrogenic acne: acne caused by amineptin (Survector)]". Annales de Dermatologie et de Vénéréologie (in French). 115 (11): 1174–6. PMID 2977079.
  12. ^ Thioly-Bensoussan D, Charpentier A, Triller R, et al. (1988). "[Iatrogenic acne caused by amineptin (Survector). Apropos of 8 cases]". Annales de Dermatologie et de Vénéréologie (in French). 115 (11): 1177–80. PMID 2977080.
  13. ^ Vexiau P, Gourmel B, Husson C, et al. (1988). "[Severe lesions of acne type induced by chronic amineptin poisoning: apropos of 6 cases]". Annales de Dermatologie et de Vénéréologie (in French). 115 (11): 1180–2. PMID 2977081.
  14. ^ Teillac D, Weber MJ, Lowenstein W, de Prost Y (1988). "[Acne caused by Survector]". Annales de Dermatologie et de Vénéréologie (in French). 115 (11): 1183–4. PMID 2977082.
  15. ^ Lévigne V, Faisant M, Mourier C, et al. (1988). "[Monstrous acne in the adult. Inducer role of Survector?]". Annales de Dermatologie et de Vénéréologie (in French). 115 (11): 1184–5. PMID 2977083.
  16. ^ Vexiau P, Gourmel B, Julien R, et al. (March 1988). "Severe acne-like lesions caused by amineptine overdose". Lancet. 1 (8585): 585. doi:10.1016/S0140-6736(88)91373-6. PMID 2894512. S2CID 32936080.
  17. ^ Martín-Ortega E, Zamora E, Herrero C, Palou J (1989). "[Acneiform eruption induced by amineptin (Survector)]". Medicina Cutánea Ibero-latino-americana (in Spanish). 17 (6): 414–6. PMID 2534534.
  18. ^ a b Vexiau P, Gourmel B, Castot A, et al. (1990). "Severe acne due to chronic amineptine overdose". Archives of Dermatological Research. 282 (2): 103–7. doi:10.1007/BF00493467. PMID 2141246. S2CID 39394890.
  19. ^ Castot A, Benzaken C, Wagniart F, Efthymiou ML (1990). "[Amineptin abuse. Analysis of 155 cases. An evaluation of the official cooperative survey of the Regional Centers of Pharmacovigilance]". Thérapie (in French). 45 (5): 399–405. PMID 2260032.
  20. ^ Deniker P, Lôo H, Zarifian E, et al. (1981). "[Amineptine and amotival syndrome (author's transl)]". L'Encéphale (in French). 7 (1): 59–64. PMID 7227285.
  21. ^ Bertschy G, Luxembourger I, Bizouard P, Vandel S, Allers G, Volmat R (1990). "[Amineptin dependence. Detection of patients at risk. Report of 8 cases]". L'Encéphale (in French). 16 (5): 405–9. PMID 2265603.
  22. ^ Blayac JP, Hillaire-Buys D, Peyrière H (1997). "[Pharmacovigilance of new antidepressants: evaluation of neuro-psychobehavioral disorders]". Thérapie. 52 (2): 117–22. PMID 9231505.
  23. ^ Castot A, Benzaken C, Wagniart F, Efthymiou ML (1990). "[Amineptin abuse. Analysis of 155 cases. An evaluation of the official cooperative survey of the Regional Centers of Pharmacovigilance]". Thérapie. 45 (5): 399–405. PMID 2260032.
  24. ^ Bertschy G, Luxembourger I, Bizouard P, Vandel S, Allers G, Volmat R (1990). "[Amineptin dependence. Detection of patients at risk. Report of 8 cases]". L'Encéphale. 16 (5): 405–9. PMID 2265603.
  25. ^ a b Bories P, Pomier-Layrargues G, Chotard JP, et al. (December 1980). "[Amineptine-induced cholestatic hepatitis. 5 cases (author's transl)]". La Nouvelle Presse Médicale (in French). 9 (48): 3689–92. PMID 7454584.
  26. ^ Pessayre D, Larrey D (April 1988). "Acute and chronic drug-induced hepatitis". Baillière's Clinical Gastroenterology. 2 (2): 385–422. doi:10.1016/0950-3528(88)90009-7. PMID 3044468.
  27. ^ Larrey D, Pageaux GP (1997). "Genetic predisposition to drug-induced hepatotoxicity". Journal of Hepatology. 26 (Suppl 2): 12–21. doi:10.1016/S0168-8278(97)80492-8. PMID 9204405.
  28. ^ "Questions au Professeur Daniel Dhumeaux" [Drug-induced liver disorders. Questions for Professor Daniel Dhumeaux]. Gastroentérologie Clinique et Biologique (in French). 23 (8–9): 917–20. 1999. PMID 10533145.
  29. ^ Concours Med 1982; 104:5733-5734[verification needed]
  30. ^ a b Sebastián Domingo JJ, Simón Marco MA, Uribarrena Echebarría R (March 1994). "Hepatic and pancreatic injury associated with amineptine therapy". Journal of Clinical Gastroenterology. 18 (2): 168–9. doi:10.1097/00004836-199403000-00023. PMID 8189020.
  31. ^ Lazaros GA, Stavrinos C, Papatheodoridis GV, Delladetsima JK, Toliopoulos A, Tassopoulos NC (1996). "Amineptine induced liver injury. Report of two cases and brief review of the literature". Hepato-gastroenterology. 43 (10): 1015–9. PMID 8884331.
  32. ^ Jonville AP, Dutertre JP, Autret E (1992). "[Immediate acute hepatic cytolysis after the administration of a single amineptin tablet]". Gastroentérologie Clinique et Biologique (in French). 16 (4): 368. PMID 1397859.
  33. ^ centres-pharmacovigilance.net 8 February 2012 at the Wayback Machine
  34. ^ Sgro C, Lacroix S, Waldner A, Lacroix M, Ferrut O, Bureau A (1989). "[Anaphylactic shock caused by amineptine. Report of a case]". La Revue de Médecine Interne (in French). 10 (5): 461–2. doi:10.1016/s0248-8663(89)80054-2. PMID 2488491.
  35. ^ 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.
  36. ^ a b c d e f g h i Garattini S, Mennini T (1989). "Pharmacology of amineptine: synthesis and updating". Clin Neuropharmacol. 12 (Suppl 2): S13–8. doi:10.1097/00002826-198912002-00003. PMID 2698268. S2CID 10947713.
  37. ^ a b c d e f Ceci A, Garattini S, Gobbi M, Mennini T (1986). "Effect of long term amineptine treatment on pre- and postsynaptic mechanisms in rat brain". Br. J. Pharmacol. 88 (1): 269–75. doi:10.1111/j.1476-5381.1986.tb09495.x. PMC 1917102. PMID 3708219.
  38. ^ a b Nishino S, Mao J, Sampathkumaran R, Shelton J (1998). "Increased dopaminergic transmission mediates the wake-promoting effects of CNS stimulants". Sleep Res Online. 1 (1): 49–61. PMID 11382857.
  39. ^ Protais P, Arbaoui J, Bakkali EH, Bermejo A, Cortes D (1995). "Effects of various isoquinoline alkaloids on in vitro 3H-dopamine uptake by rat striatal synaptosomes". J. Nat. Prod. 58 (10): 1475–84. doi:10.1021/np50124a001. PMID 8676127.
  40. ^ a b c d e f g h i Hall H, Sällemark M, Wedel I (1984). "Acute effects of atypical antidepressants on various receptors in the rat brain". Acta Pharmacol Toxicol (Copenh). 54 (5): 379–84. doi:10.1111/j.1600-0773.1984.tb01945.x. PMID 6464782.
  41. ^ a b Hall H, Ogren SO (1984). "Effects of antidepressant drugs on histamine-H1 receptors in the brain". Life Sci. 34 (6): 597–605. doi:10.1016/0024-3205(84)90494-6. PMID 6141518.
  42. ^ a b c d e f Garattini S (1997). "Pharmacology of amineptine, an antidepressant agent acting on the dopaminergic system: a review". Int Clin Psychopharmacol. 12 (Suppl 3): S15–9. doi:10.1097/00004850-199707003-00003. PMID 9347388. S2CID 23014661.
  43. ^ Andersen J, Kristensen AS, Bang-Andersen B, Strømgaard K (2009). "Recent advances in the understanding of the interaction of antidepressant drugs with serotonin and norepinephrine transporters". Chem. Commun. (25): 3677–92. doi:10.1039/b903035m. PMID 19557250.
  44. ^ . Archived from the original on 3 December 2021. Retrieved 30 November 2021.
  45. ^ "Federal Register". Federal Register. National Archives & Drug Enforcement Administration. 17 November 2022.

April 11, 2024
amineptine, formerly, sold, under, brand, name, survector, among, others, atypical, antidepressant, tricyclic, antidepressant, family, acts, selective, mixed, dopamine, reuptake, inhibitor, releasing, agent, lesser, extent, norepinephrine, reuptake, inhibitor,. Amineptine formerly sold under the brand name Survector among others is an atypical antidepressant of the tricyclic antidepressant TCA family 4 5 It acts as a selective and mixed dopamine reuptake inhibitor and releasing agent and to a lesser extent as a norepinephrine reuptake inhibitor 4 5 AmineptineClinical dataTrade namesSurvector othersOther namesS 1694Routes ofadministrationOralATC codeN06AA19 WHO Legal statusLegal statusAU Unscheduled BR Class B1 Psychoactive drugs 1 CA Schedule III DE Anlage II Authorized trade only not prescriptible UK Class C US Schedule I UN Psychotropic Schedule IIPharmacokinetic dataMetabolismHepaticElimination half lifeAmineptine 0 8 1 0 hours 2 3 Metabolite 1 5 2 5 hours 2 3 ExcretionRenalIdentifiersIUPAC name 7 10 11 dihydro 5H dibenzo a d cyclohepten 5 yl amino heptanoic acidCAS Number57574 09 1 YPubChem CID34870DrugBankDB04836 YChemSpider32091 YUNII27T1I13L6GKEGGD07335 YChEBICHEBI 32499 YChEMBLChEMBL418995 YCompTox Dashboard EPA DTXSID1048831ECHA InfoCard100 055 271Chemical and physical dataFormulaC 22H 28N O 2Molar mass338 471 g mol 13D model JSmol Interactive imageSMILES O C O CCCCCCNC1c2ccccc2CCc2ccccc21InChI InChI 1S C22H27NO2 c24 21 25 13 3 1 2 8 16 23 22 19 11 6 4 9 17 19 14 15 18 10 5 7 12 20 18 22 h4 7 9 12 22 23H 1 3 8 13 16H2 H 24 25 YKey ONNOFKFOZAJDHT UHFFFAOYSA N Y verify Amineptine was developed by the French Society of Medical research in the 1960s 6 Introduced in France in 1978 by the pharmaceutical company Servier 7 amineptine soon gained a reputation for abuse due to its short lived but pleasant stimulant effect experienced by some patients After its release into the European market cases of hepatotoxicity emerged some serious This along with the potential for abuse led to the suspension of the French marketing authorization for Survector in 1999 8 Amineptine is illegal in both Germany and the United States Contents 1 Medical uses 2 Contraindications 2 1 Precautions for use 2 2 Effects on the fetus 3 Side effects 3 1 Dermatological 3 2 Psychiatric 3 2 1 Abuse and dependence 3 2 2 Withdrawal 3 3 Cardiovascular 3 4 Hepatic 3 5 Gastrointestinal 3 6 Immunological 4 Pharmacology 4 1 Pharmacodynamics 4 2 Pharmacokinetics 5 Society and culture 5 1 Brand names 5 2 Legal status 6 ReferencesMedical uses editAmineptine was approved in France for severe clinical depression of endogenous origin in 1978 9 Contraindications editChorea Hypersensitivity Known hypersensitivity to amineptine in particular antecedents of hepatitis after dosage of the product MAO inhibitorsPrecautions for use edit Warnings and precautions before taking amineptine 10 Breast feeding Children less than 15 year of age General anaesthesia Discontinue the drug 24 to 48 hours before anaesthesia citation needed Official sports Olympic Games Prohibited substance 7 March Official Journal 2000 Pregnancy first trimester citation needed Effects on the fetus edit Lacking information in humans Non teratogenic in rodentsSide effects editDermatological edit Severe acne due to amineptine was first reported in 1988 by various authors Grupper Thioly Bensoussan Vexiau Fiet Puissant Gourmel Teillac Levigne to name a few simultaneously 11 12 13 14 15 in the same issue of Annales de Dermatologie et de Venereologie and in the 12 March 1988 issue of The Lancet 16 A year later Dr Martin Ortega and colleagues in Barcelona Spain reported a case of acneiform eruption in a 54 year old woman whose intake of amineptine was described as excessive 17 One year after that Vexiau and colleagues reported six women one of whom never admitted to using amineptine getting severe acne concentrated in the face back and thorax the severity of which varied with the dosage 18 Most of them were treated unsuccessfully with isotretinoin Accutane for about 18 months two of the three that discontinued amineptine experienced a reduction in cutaneous symptoms with the least affected patient going into remission 18 Psychiatric edit Psychomotor excitation can very rarely occur with this drug Insomnia Irritability Nervousness Suicidal ideation Seen early in the treatment by lifting of psychomotor inhibition Abuse and dependence edit The risk of addiction is low but exists nonetheless Between 1978 and 1988 there were 186 cases of amineptine addiction reported to the French Regional Centres of Pharmacovigilance an analysis of 155 of those cases found that they were predominantly female and that two thirds of cases had known risk factors for addiction 19 However a 1981 study of known opiate addicts and schizophrenia patients found no drug addiction in any of the subjects 20 In a 1990 study of eight amineptine dependence cases the gradual withdrawal of amineptine could be achieved without problems in six people in two others anxiety psychomotor agitation and or bulimia appeared 21 Withdrawal edit Pharmacodependence is very common with amineptine compared to other antidepressants 22 A variety of psychological symptoms can occur during withdrawal from amineptine 23 such as anxiety and agitation 24 Cardiovascular edit Very rarely Arterial hypotension Palpitations Vasomotor episodeHepatic edit Amineptine can rarely cause hepatitis of the cytolytic cholestatic varieties 25 Amineptine induced hepatitis which is sometimes preceded by a rash is believed to be due to an immunoallergic reaction 26 It resolves upon discontinuation of the offending drug 25 The risk of getting this may or may not be genetically determined 27 Additionally amineptine is known to rarely elevate transaminases alkaline phosphatase and bilirubin 28 Mixed hepatitis which is very rare generally occurs between the 15th and 30th day of treatment Often preceded by sometimes intense abdominal pains nausea vomiting or a rash the jaundice is variable Hepatitis is either of mixed type or with cholestatic prevalence The evolution was in all the cases favorable to the discontinuation of the drug The mechanism is discussed immunoallergic and or toxic 29 In circa 1994 Spain there was a case associating acute pancreatitis and mixed hepatitis after three weeks of treatment 30 Lazaros and colleagues at the Western Attica General Hospital in Athens Greece reported two cases of drug induced hepatitis 18 and 15 days of treatment 31 One case of cytolytic hepatitis occurred after ingestion of only one tablet 32 Gastrointestinal edit Acute pancreatitis very rare A case associating acute pancreatitis and mixed hepatitis after three weeks of treatment 30 Immunological edit In 1989 Sgro and colleagues at the Centre de Pharmacovigilance 33 in Dijon reported a case of anaphylactic shock in a woman who had been taking amineptine 34 Pharmacology editPharmacodynamics edit Amineptine 35 Site Ki nM Species RefSERTTooltip Serotonin transporter gt 100 000 IC50 Rat 36 NETTooltip Norepinephrine transporter 10 000 IC50 3 560 RatCanine 36 37 38 DATTooltip Dopamine transporter 1 000 1 400 IC50 3 330 RatCanine 36 39 37 38 5 HT1A gt 100 000 Rat 40 5 HT2A 74 000 Rat 40 a1 gt 100 000 Rat 40 a2 gt 100 000 Rat 40 b gt 100 000 Rat 40 D1 gt 100 000 Canine 36 D2 gt 100 000 Rat canine 36 40 H1 gt 100 00013 000 RatGuinea pig 40 41 mAChTooltip Muscarinic acetylcholine receptor gt 100 000 Rat 40 Values are Ki nM unless otherwise noted The smaller the value the more strongly the drug binds to the site Amineptine inhibits the reuptake of dopamine and to a much lesser extent of norepinephrine 37 36 42 In addition it has been found to induce the release of dopamine 37 36 42 However amineptine is much less efficacious as a dopamine releasing agent relative to D amphetamine and the drug appears to act predominantly as a dopamine reuptake inhibitor 37 36 42 In contrast to the case for dopamine amineptine does not induce the release of norepinephrine and hence acts purely as a norepinephrine reuptake inhibitor 37 36 42 Unlike other TCAs amineptine interacts very weakly or not at all with the serotonin adrenergic dopamine histamine and muscarinic acetylcholine receptors 40 41 42 The major metabolites of amineptine have similar activity to that of the parent compound albeit with lower potency 42 No human data appear to be available for binding or inhibition of the monoamine transporters by amineptine 43 Pharmacokinetics edit Peak plasma levels of amineptine following a single 100 mg oral dose have been found to range between 277 and 2 215 ng mL 818 6 544 nM with a mean of 772 ng mL 2 281 nM whereas maximal plasma concentrations of its major metabolite ranged between 144 and 1 068 ng mL 465 3 452 nM with a mean of 471 ng mL 1 522 nM 2 After a single 200 mg oral dose of amineptine mean peak plasma levels of amineptine were around 750 to 940 ng mL 2 216 2 777 nM while those of its major metabolite were about 750 to 970 ng mL 2 216 3 135 nM 3 The time to peak concentrations is about 1 hour for amineptine and 1 5 hours for its major metabolite 2 3 The elimination half life of amineptine is about 0 80 to 1 0 hours and that of its major metabolite is about 1 5 to 2 5 hours 2 3 Due to their very short elimination half lives amineptine and its major metabolite do not accumulate significantly with repeated administration 2 Society and culture editBrand names edit Amineptine has been sold under a variety of brand names including Survector Maneon Directim Neolior Provector and Viaspera Legal status edit It had been proposed that Amineptine become a Schedule I controlled substance in the United States in July 2021 44 This announcement was followed by the placement of Amineptine into Schedule I 45 References edit 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 a b c d e f Lachatre G Piva C Riche C et al 1989 Single dose pharmacokinetics of amineptine and of its main metabolite in healthy young adults Fundam Clin Pharmacol 3 1 19 26 doi 10 1111 j 1472 8206 1989 tb00026 x PMID 2714729 S2CID 25992333 a b c d e Sbarra C Castelli MG Noseda A Fanelli R 1981 Pharmacokinetics of amineptine in man Eur J Drug Metab Pharmacokinet 6 2 123 6 doi 10 1007 bf03189478 PMID 7274306 S2CID 31069503 a b Vaugeois JM Corera AT Deslandes A Costentin J June 1999 Although chemically related to amineptine the antidepressant tianeptine is not a dopamine uptake inhibitor Pharmacology Biochemistry and Behavior 63 2 285 90 doi 10 1016 S0091 3057 98 00242 1 PMID 10371658 S2CID 32862145 a b Dunlop BW Nemeroff CB 2007 The role of dopamine in the pathophysiology of depression Arch Gen Psychiatry 64 3 327 37 doi 10 1001 archpsyc 64 3 327 PMID 17339521 S2CID 26550661 DE Patent 2011806 NEW TRICYCLIC DERIVATIVES AND PROCESS FOR THEIR MANUFACTURE Sittig M 1 April 1988 1979 Pharmaceutical Manufacturing Encyclopedia 2nd ed Park Ridge New Jersey United States American William Andrew Publishing Noyes Publications ISBN 978 0 8155 1144 1 Archived from the original on 23 October 2005 Retrieved 29 October 2005 page needed Docket No 02N 0101 U S Food and Drug Administration 9 April 2002 Retrieved 30 January 2014 Doctissimo 2005 SURVECTOR Amineptine in French Archived from the original on 9 March 2005 Retrieved 27 October 2005 Amineptine Medication Uses Side Effects and Precautions of Amineptine Health care information org Retrieved on 28 September 2013 Grupper C 1988 New iatrogenic acne acne caused by amineptin Survector Annales de Dermatologie et de Venereologie in French 115 11 1174 6 PMID 2977079 Thioly Bensoussan D Charpentier A Triller R et al 1988 Iatrogenic acne caused by amineptin Survector Apropos of 8 cases Annales de Dermatologie et de Venereologie in French 115 11 1177 80 PMID 2977080 Vexiau P Gourmel B Husson C et al 1988 Severe lesions of acne type induced by chronic amineptin poisoning apropos of 6 cases Annales de Dermatologie et de Venereologie in French 115 11 1180 2 PMID 2977081 Teillac D Weber MJ Lowenstein W de Prost Y 1988 Acne caused by Survector Annales de Dermatologie et de Venereologie in French 115 11 1183 4 PMID 2977082 Levigne V Faisant M Mourier C et al 1988 Monstrous acne in the adult Inducer role of Survector Annales de Dermatologie et de Venereologie in French 115 11 1184 5 PMID 2977083 Vexiau P Gourmel B Julien R et al March 1988 Severe acne like lesions caused by amineptine overdose Lancet 1 8585 585 doi 10 1016 S0140 6736 88 91373 6 PMID 2894512 S2CID 32936080 Martin Ortega E Zamora E Herrero C Palou J 1989 Acneiform eruption induced by amineptin Survector Medicina Cutanea Ibero latino americana in Spanish 17 6 414 6 PMID 2534534 a b Vexiau P Gourmel B Castot A et al 1990 Severe acne due to chronic amineptine overdose Archives of Dermatological Research 282 2 103 7 doi 10 1007 BF00493467 PMID 2141246 S2CID 39394890 Castot A Benzaken C Wagniart F Efthymiou ML 1990 Amineptin abuse Analysis of 155 cases An evaluation of the official cooperative survey of the Regional Centers of Pharmacovigilance Therapie in French 45 5 399 405 PMID 2260032 Deniker P Loo H Zarifian E et al 1981 Amineptine and amotival syndrome author s transl L Encephale in French 7 1 59 64 PMID 7227285 Bertschy G Luxembourger I Bizouard P Vandel S Allers G Volmat R 1990 Amineptin dependence Detection of patients at risk Report of 8 cases L Encephale in French 16 5 405 9 PMID 2265603 Blayac JP Hillaire Buys D Peyriere H 1997 Pharmacovigilance of new antidepressants evaluation of neuro psychobehavioral disorders Therapie 52 2 117 22 PMID 9231505 Castot A Benzaken C Wagniart F Efthymiou ML 1990 Amineptin abuse Analysis of 155 cases An evaluation of the official cooperative survey of the Regional Centers of Pharmacovigilance Therapie 45 5 399 405 PMID 2260032 Bertschy G Luxembourger I Bizouard P Vandel S Allers G Volmat R 1990 Amineptin dependence Detection of patients at risk Report of 8 cases L Encephale 16 5 405 9 PMID 2265603 a b Bories P Pomier Layrargues G Chotard JP et al December 1980 Amineptine induced cholestatic hepatitis 5 cases author s transl La Nouvelle Presse Medicale in French 9 48 3689 92 PMID 7454584 Pessayre D Larrey D April 1988 Acute and chronic drug induced hepatitis Bailliere s Clinical Gastroenterology 2 2 385 422 doi 10 1016 0950 3528 88 90009 7 PMID 3044468 Larrey D Pageaux GP 1997 Genetic predisposition to drug induced hepatotoxicity Journal of Hepatology 26 Suppl 2 12 21 doi 10 1016 S0168 8278 97 80492 8 PMID 9204405 Questions au Professeur Daniel Dhumeaux Drug induced liver disorders Questions for Professor Daniel Dhumeaux Gastroenterologie Clinique et Biologique in French 23 8 9 917 20 1999 PMID 10533145 Concours Med 1982 104 5733 5734 verification needed a b Sebastian Domingo JJ Simon Marco MA Uribarrena Echebarria R March 1994 Hepatic and pancreatic injury associated with amineptine therapy Journal of Clinical Gastroenterology 18 2 168 9 doi 10 1097 00004836 199403000 00023 PMID 8189020 Lazaros GA Stavrinos C Papatheodoridis GV Delladetsima JK Toliopoulos A Tassopoulos NC 1996 Amineptine induced liver injury Report of two cases and brief review of the literature Hepato gastroenterology 43 10 1015 9 PMID 8884331 Jonville AP Dutertre JP Autret E 1992 Immediate acute hepatic cytolysis after the administration of a single amineptin tablet Gastroenterologie Clinique et Biologique in French 16 4 368 PMID 1397859 centres pharmacovigilance net Archived 8 February 2012 at the Wayback Machine Sgro C Lacroix S Waldner A Lacroix M Ferrut O Bureau A 1989 Anaphylactic shock caused by amineptine Report of a case La Revue de Medecine Interne in French 10 5 461 2 doi 10 1016 s0248 8663 89 80054 2 PMID 2488491 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 g h i Garattini S Mennini T 1989 Pharmacology of amineptine synthesis and updating Clin Neuropharmacol 12 Suppl 2 S13 8 doi 10 1097 00002826 198912002 00003 PMID 2698268 S2CID 10947713 a b c d e f Ceci A Garattini S Gobbi M Mennini T 1986 Effect of long term amineptine treatment on pre and postsynaptic mechanisms in rat brain Br J Pharmacol 88 1 269 75 doi 10 1111 j 1476 5381 1986 tb09495 x PMC 1917102 PMID 3708219 a b Nishino S Mao J Sampathkumaran R Shelton J 1998 Increased dopaminergic transmission mediates the wake promoting effects of CNS stimulants Sleep Res Online 1 1 49 61 PMID 11382857 Protais P Arbaoui J Bakkali EH Bermejo A Cortes D 1995 Effects of various isoquinoline alkaloids on in vitro 3H dopamine uptake by rat striatal synaptosomes J Nat Prod 58 10 1475 84 doi 10 1021 np50124a001 PMID 8676127 a b c d e f g h i Hall H Sallemark M Wedel I 1984 Acute effects of atypical antidepressants on various receptors in the rat brain Acta Pharmacol Toxicol Copenh 54 5 379 84 doi 10 1111 j 1600 0773 1984 tb01945 x PMID 6464782 a b Hall H Ogren SO 1984 Effects of antidepressant drugs on histamine H1 receptors in the brain Life Sci 34 6 597 605 doi 10 1016 0024 3205 84 90494 6 PMID 6141518 a b c d e f Garattini S 1997 Pharmacology of amineptine an antidepressant agent acting on the dopaminergic system a review Int Clin Psychopharmacol 12 Suppl 3 S15 9 doi 10 1097 00004850 199707003 00003 PMID 9347388 S2CID 23014661 Andersen J Kristensen AS Bang Andersen B Stromgaard K 2009 Recent advances in the understanding of the interaction of antidepressant drugs with serotonin and norepinephrine transporters Chem Commun 25 3677 92 doi 10 1039 b903035m PMID 19557250 2021 Placement of Amineptine in Schedule I Archived from the original on 3 December 2021 Retrieved 30 November 2021 Federal Register Federal Register National Archives amp Drug Enforcement Administration 17 November 2022 Retrieved from https en wikipedia org w index php title Amineptine amp oldid 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