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Salvinorin A

January 01, 1970

Salvinorin A is the main active psychotropic molecule in Salvia divinorum. Salvinorin A is considered a dissociative hallucinogen.[3][4]

Salvinorin A
Clinical data
Routes of
administration		Buccal/Sublingual, Smoked
ATC code
  • none
Legal status
Legal status
Identifiers
  • methyl (2S,4aR,6aR,7R,9S,10aS,10bR)-9-(acetyloxy)-2-(furan-3-yl)-6a,10b-dimethyl-4,10-dioxo-dodecahydro-1H-naphtho[2,1-c]pyran-7-carboxylate
CAS Number
  • 83729-01-5 N
PubChem CID
  • 128563
IUPHAR/BPS
  • 1666
ChemSpider
  • 113947 Y
UNII
  • T56W91NG6J
KEGG
  • C20196 N
ChEBI
  • CHEBI:67900 N
ChEMBL
  • ChEMBL445332 Y
CompTox Dashboard (EPA)
  • DTXSID80232584
ECHA InfoCard100.215.796
Chemical and physical data
FormulaC23H28O8
Molar mass432.469 g·mol−1
3D model (JSmol)
  • Interactive image
Specific rotation[α]D = -45.3° at 22 °C/ (c = 8.530 CHCl3); [α]D = -41° at 25 °C (c = 1 in CHCl3)
Melting point238 to 240 °C (460 to 464 °F) (also reported 242–244 °C)[2]
Boiling point760.2 °C (1,400.4 °F)
Solubility in water25.07 mg/L at 25 °C (water, est) mg/mL (20 °C)
  • O=C(OC)[C@H]2[C@@]3(CC[C@H]4C(=O)O[C@H](c1ccoc1)C[C@@]4([C@H]3C(=O)[C@@H](OC(=O)C)C2)C)C
  • InChI=1S/C23H28O8/c1-12(24)30-16-9-15(20(26)28-4)22(2)7-5-14-21(27)31-17(13-6-8-29-11-13)10-23(14,3)19(22)18(16)25/h6,8,11,14-17,19H,5,7,9-10H2,1-4H3/t14-,15-,16-,17-,19-,22-,23-/m0/s1 Y
  • Key:OBSYBRPAKCASQB-AGQYDFLVSA-N Y
 NY (what is this?)  (verify)

It is structurally distinct from other naturally occurring hallucinogens (such as DMT, psilocybin, and mescaline) because it contains no nitrogen atoms; hence, it is not an alkaloid (and cannot be rendered as a salt), but rather is a terpenoid.[3] It also differs in subjective experience, compared to other hallucinogens, and has been described as dissociative.[4]

Salvinorin A can produce psychoactive experiences in humans with a typical duration of action being several minutes to an hour or so, depending on the method of ingestion.[5]

Salvinorin A is found with several other structurally related salvinorins. Salvinorin is a trans-neoclerodane diterpenoid. It acts as a kappa opioid receptor agonist and is the first known compound acting on this receptor that is not an alkaloid.[5]

History edit

Salvinorin A was first described and named in 1982 by Alfredo Ortega and colleagues in Mexico. They used a combination of spectroscopy and x-ray crystallography to determine the chemical structure of the compound, which was shown to have a bicyclic diterpene structure.[6] Around the same time, Leander Julián Valdés III independently isolated the molecule as part of his PhD research, published in 1983.[7] Valdés named the chemical divinorin, and also isolated an analog that he named divinorin B. The naming was subsequently corrected to salvinorin A and B after the work was published in 1984.[8] Valdés later isolated salvinorin C.[9]

Pharmacology edit

Salvinorin A is a trans-neoclerodane diterpenoid with the chemical formula C23H28O8.[10] Unlike other known opioid-receptor ligands, salvinorin A is not an alkaloid, as it does not contain a basic nitrogen atom.[3][11] Salvinorin A has no action at the 5-HT2A serotonin receptor, the principal molecular target responsible for the actions of 'classical' psychedelics such as LSD and mescaline.[5][11] Salvinorin A has also been shown to have effect on cannabinoid CB1 receptors.[12] It significantly increases prolactin and inconsistently increases cortisol.[13] It causes dysphoria by stopping release of dopamine in the striatum.[14] Salvinorin A increases activity of DAT while decreasing activity of SERT.[14]

Pharmacokinetics edit

Salvinorin A is effectively deactivated by the gastrointestinal system, so alternative routes of administration must be used for better absorption. It is absorbed by oral mucosa.[15] It has a half-life of around 8 minutes in non-human primates.[16]

Potency and selectivity edit

Salvinorin A is active at doses as low as 200 µg.[10][17][18] Synthetic chemicals, such as LSD (active at 20–30 µg doses), can be more potent.[19] Research has shown that salvinorin A is a potent κ-opioid receptor (KOR) agonist (Ki = 2.4 nM, EC50 = 1.8 nM).[10] It has a high affinity for the receptor, indicated by the low dissociation constant of 1.0 nanomolar (nM).[20] It has been reported that the effects of salvinorin A in mice are blocked by κ-opioid receptor antagonists.[21] In addition, salvinorin A has recently been found to act as a D2 receptor partial agonist, with an affinity of 5–10 nM, an intrinsic activity of 40–60%, and an EC50 of 48 nM.[22] This suggests that the D2 receptor may also play an important role in its effects.[22] Salvinorin A shows atypical properties as an agonist of the KOR relative to other KOR agonists.[23] For instance, it is 40-fold less potent in promoting internalization (receptor downregulation) of the human KOR relative to the prototypical KOR agonist U-50488.[citation needed]

Effect on intestinal motility edit

Salvinorin A is capable of inhibiting excess intestinal motility (e.g. diarrhea), through its potent κ-opioid-activating effects. The mechanism of action for salvinorin A on ileal tissue has been described as 'prejunctional', as it was able to modify electrically induced contractions, but not those of exogenous acetylcholine.[24] A pharmacologically important aspect of the contraction-reducing properties of ingested salvinorin A on gut tissue is that it is only pharmacologically active on inflamed and not normal tissue, thus reducing possible side-effects.[25]

Solubility edit

Salvinorin A is soluble in organic solvents such as ethanol and acetone, but not especially so in water.[26]

Detection in urine edit

Researchers found that humans who smoked 580 μg of the pure drug had urine salvinorin A concentrations of 2.4–10.9 µg/L during the first hour; the levels fell below the detection limit by 1.5 hours after smoking.[27]

Research edit

Salvinorin A has only been administered to humans in a few studies, one showing that its effects peaked at about 2 minutes, that its subjective effects may overlap with those of serotonergic psychedelics, and that it temporarily impairs recall and recognition memory.[4] Like most other agonists of kappa opioid receptors, salvinorin A produces sedation, psychotomimesis, dysphoria, anhedonia, and depression.[3][28][29] Salvinorin A has been screened for its possible use as a structural "scaffold" in medicinal chemistry in developing new drugs for treating psychiatric diseases[3][30] such as cocaine dependence.[31]

Synthesis edit

 
Salvinorin A

Biosynthesis edit

The biogenic origin of salvinorin A synthesis has been elucidated using nuclear magnetic resonance and ESI-MS analysis of incorporated precursors labeled with stable isotopes of carbon (carbon-13 13C) and hydrogen (deuterium 2H). It "is biosynthesized via the 1-deoxy-d-xylulose-5-phosphate pathway", rather than the classic mevalonate pathway, consistent with the common plastidial localization of diterpenoid metabolism.[32]

Terpenoids are biosynthesized from two 5-carbon precursors, isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). The NMR and MS study by Zjawiony suggested that the biosynthesis of salvinorin A proceeds via the 1-deoxy-d-xylulose-5-phosphate pathway. In the deoxyxylulose phosphate pathway, D-glyceraldehyde 3-phosphate and pyruvate, the intermediates of the glycolysis, are converted into 1-deoxy-D-xylulose 5-phosphate via decarboxylation. Subsequent reduction with NADPH generates 2C-methyl-D-erythritol 2,4-cyclodiphosphate, via the intermediates 4-diphosphocytidyl-2-C-methyl-D-erythritol and 4-diphosphocytidyl-2c-methyl-d-erythritol-2-phosphate, which then lead to IPP and DMAPP.

 
Synthesis of IPP and DMAPP via 1-deoxy-d-xylulose-5-phosphate pathway

Subsequent addition of three 5-carbon IPP units to a single 5-carbon DMAPP unit generates the 20-carbon central precursor, geranylgeranyl diphosphate (GGPP). Bicyclization of GGPP by the class II diterpene synthase, ent-clerodienyl diphosphate synthase (SdCPS2[33]), produces a labdanyl diphosphate carbocation, which is subsequently rearranged through a sequence of 1,2-hydride and methyl shifts to form the ent-clerodienyl diphosphate intermediate.[34] SdCPS2 catalyzes the first committed reaction in the biosynthesis of salvinorin A by producing its characteristic clerodane scaffold. A series of oxygenation, acylation and methylation reactions is then required to complete the biosynthesis of salvinorin A.[33]

 
Biosynthesis of salvinorin A

Similar to many plant-derived psychoactive compounds, salvinorin A is excreted via peltate glandular trichomes, which reside external to the epidermis.[35][36]

Chemical synthesis edit

A total asymmetric synthesis of salvinorin A, which relies on a transannular Michael reaction cascade to construct the ring system, was achieved as a 4.5% overall yield over 30 steps,[37] then revised using 24 steps to yield salvinorin A in 0.15% yield.[38] An approach to the trans-decalin ring system of salvinorin A used an intramolecular Diels-Alder reaction/Tsuji allylation strategy,[39] and a total synthesis of salvinorin A was achieved using the intramolecular Diels-Alder / Tsuji allylation approach, combined with an asymmetric late-stage addition of the furan moiety.[40]

Associated compounds edit

Main article: Salvinorin

Salvinorin A is one of several structurally related salvinorins found in the Salvia divinorum plant. Salvinorin A is the only naturally occurring salvinorin that is known to be psychoactive.[41] Salvinorin A can be synthesized from salvinorin B by acetylation, and de-acetylated salvinorin A becomes analog to salvinorin B.[42]

Research has produced a number of semi-synthetic compounds. Most derivatives are selective kappa opioid agonists as with salvinorin A, although some are even more potent, with the most potent compound salvinorin B ethoxymethyl ether being ten times stronger than salvinorin A. Some derivatives, such as herkinorin, reduce kappa opioid action and instead act as mu opioid agonists.[43][44][45][46]

The synthetic derivative RB-64 is notable because of its functional selectivity and potency.[47] Salvinorin B methoxymethyl ether is seven times more potent than salvinorin A at KOPr in GTP-γS assays.[48]

Natural occurrence edit

Salvinorin A occurs naturally in several Salvia species:

Salvinorin B has been detected in S. potentillifolia and S. adenocaulon, however these species do not contain a measureable amount of salvinorin A.[50]

Legal status edit

See also: Legal status of Salvia divinorum

Salvinorin A is sometimes regulated together with its host, Salvia divinorum, due to its psychoactive and analgesic effects.

United States edit

See also: Legal status of Salvia divinorum in the United States

Salvinorin A is not scheduled at the federal level in the United States.[51] Its molecular structure is unlike any Schedule I or II drug, so possession or sales is unlikely to be prosecuted under the Federal Analogue Act.[citation needed]

Florida edit

"Salvinorin A" is a Schedule I controlled substance in the state of Florida making it illegal to buy, sell, or possess in Florida. There is an exception however for "any drug product approved by the United States Food and Drug Administration which contains salvinorin A or its isomers, esters, ethers, salts, and salts of isomers, esters, and ethers, if the existence of such isomers, esters, ethers, and salts is possible within the specific chemical designation."[52]

Australia edit

Salvinorin A is considered a Schedule 9 prohibited substance in Australia under the Poisons Standard (October 2015).[53] A Schedule 9 substance is a substance which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities.[53]

Sweden edit

Sveriges riksdags health ministry Statens folkhälsoinstitut classified salvinorin A (and Salvia divinorum) as "health hazard" under the act Lagen om förbud mot vissa hälsofarliga varor (translated Act on the Prohibition of Certain Goods Dangerous to Health) as of April 1, 2006, in their regulation SFS 2006:167 listed as "salvinorin A", making it illegal to sell or possess.[54]

See also edit

References edit

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  49. ^ Brito-da-Costa AM, Dias-da-Silva D, Gomes NG, Dinis-Oliveira RJ, Madureira-Carvalho Á (February 2021). "Pharmacokinetics and Pharmacodynamics of Salvinorin A and Salvia divinorum: Clinical and Forensic Aspects". Pharmaceuticals. 14 (2): 116. doi:10.3390/ph14020116. PMC 7913753. PMID 33546518.
  50. ^ a b c d Hatipoglu SD, Yalcinkaya B, Akgoz M, Ozturk T, Goren AC, Topcu G (November 2017). "Screening of Hallucinogenic Compounds and Genomic Characterisation of 40 Anatolian Salvia Species". Phytochemical Analysis. 28 (6): 541–549. Bibcode:2017PChAn..28..541H. doi:10.1002/pca.2703. PMID 28722248.
  51. ^ Archived from the original on 2009-08-27. Retrieved 2014-12-18.
  52. ^ "Statutes & Constitution :View Statutes : Online Sunshine". leg.state.fl.us.
  53. ^ a b "Poisons Standard". The Australian Government. October 2015.
  54. ^ [Ordinance amending the ordinance (1999: 58) on the prohibition of certain dangerous goods] (PDF) (in Swedish). Svensk författningssamling. 2006. Archived from the original (PDF) on 2013-09-29. Retrieved 2013-09-25.

Further reading edit

  • Baselt RC (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 1405–6. ISBN 978-0-9626523-7-0.

January 01, 1970
salvinorin, main, active, psychotropic, molecule, salvia, divinorum, considered, dissociative, hallucinogen, clinical, dataroutes, ofadministrationbuccal, sublingual, smokedatc, codenonelegal, statuslegal, statusau, prohibited, substance, class, prohibited, ps. Salvinorin A is the main active psychotropic molecule in Salvia divinorum Salvinorin A is considered a dissociative hallucinogen 3 4 Salvinorin AClinical dataRoutes ofadministrationBuccal Sublingual SmokedATC codenoneLegal statusLegal statusAU S9 Prohibited substance BR Class F2 Prohibited psychotropics 1 CA Schedule IV UK Under Psychoactive Substances Act Uncontrolled though Salvia divinorum is controlled in some parts of the world such as in certain states in the US IdentifiersIUPAC name methyl 2S 4aR 6aR 7R 9S 10aS 10bR 9 acetyloxy 2 furan 3 yl 6a 10b dimethyl 4 10 dioxo dodecahydro 1H naphtho 2 1 c pyran 7 carboxylateCAS Number83729 01 5 NPubChem CID128563IUPHAR BPS1666ChemSpider113947 YUNIIT56W91NG6JKEGGC20196 NChEBICHEBI 67900 NChEMBLChEMBL445332 YCompTox Dashboard EPA DTXSID80232584ECHA InfoCard100 215 796Chemical and physical dataFormulaC 23H 28O 8Molar mass432 469 g mol 13D model JSmol Interactive imageSpecific rotation a D 45 3 at 22 C c 8 530 CHCl3 a D 41 at 25 C c 1 in CHCl3 Melting point238 to 240 C 460 to 464 F also reported 242 244 C 2 Boiling point760 2 C 1 400 4 F Solubility in water25 07 mg L at 25 C water est mg mL 20 C SMILES O C OC C H 2 C 3 CC C H 4C O O C H c1ccoc1 C C 4 C H 3C O C H OC O C C2 C CInChI InChI 1S C23H28O8 c1 12 24 30 16 9 15 20 26 28 4 22 2 7 5 14 21 27 31 17 13 6 8 29 11 13 10 23 14 3 19 22 18 16 25 h6 8 11 14 17 19H 5 7 9 10H2 1 4H3 t14 15 16 17 19 22 23 m0 s1 YKey OBSYBRPAKCASQB AGQYDFLVSA N Y N Y what is this verify It is structurally distinct from other naturally occurring hallucinogens such as DMT psilocybin and mescaline because it contains no nitrogen atoms hence it is not an alkaloid and cannot be rendered as a salt but rather is a terpenoid 3 It also differs in subjective experience compared to other hallucinogens and has been described as dissociative 4 Salvinorin A can produce psychoactive experiences in humans with a typical duration of action being several minutes to an hour or so depending on the method of ingestion 5 Salvinorin A is found with several other structurally related salvinorins Salvinorin is a trans neoclerodane diterpenoid It acts as a kappa opioid receptor agonist and is the first known compound acting on this receptor that is not an alkaloid 5 Contents 1 History 2 Pharmacology 2 1 Pharmacokinetics 2 2 Potency and selectivity 2 3 Effect on intestinal motility 2 4 Solubility 2 5 Detection in urine 3 Research 4 Synthesis 4 1 Biosynthesis 4 2 Chemical synthesis 5 Associated compounds 6 Natural occurrence 7 Legal status 7 1 United States 7 1 1 Florida 7 2 Australia 7 3 Sweden 8 See also 9 References 10 Further readingHistory editSalvinorin A was first described and named in 1982 by Alfredo Ortega and colleagues in Mexico They used a combination of spectroscopy and x ray crystallography to determine the chemical structure of the compound which was shown to have a bicyclic diterpene structure 6 Around the same time Leander Julian Valdes III independently isolated the molecule as part of his PhD research published in 1983 7 Valdes named the chemical divinorin and also isolated an analog that he named divinorin B The naming was subsequently corrected to salvinorin A and B after the work was published in 1984 8 Valdes later isolated salvinorin C 9 Pharmacology editSalvinorin A is a trans neoclerodane diterpenoid with the chemical formula C23H28O8 10 Unlike other known opioid receptor ligands salvinorin A is not an alkaloid as it does not contain a basic nitrogen atom 3 11 Salvinorin A has no action at the 5 HT2A serotonin receptor the principal molecular target responsible for the actions of classical psychedelics such as LSD and mescaline 5 11 Salvinorin A has also been shown to have effect on cannabinoid CB1 receptors 12 It significantly increases prolactin and inconsistently increases cortisol 13 It causes dysphoria by stopping release of dopamine in the striatum 14 Salvinorin A increases activity of DAT while decreasing activity of SERT 14 Pharmacokinetics edit Salvinorin A is effectively deactivated by the gastrointestinal system so alternative routes of administration must be used for better absorption It is absorbed by oral mucosa 15 It has a half life of around 8 minutes in non human primates 16 Potency and selectivity edit Salvinorin A is active at doses as low as 200 µg 10 17 18 Synthetic chemicals such as LSD active at 20 30 µg doses can be more potent 19 Research has shown that salvinorin A is a potent k opioid receptor KOR agonist Ki 2 4 nM EC50 1 8 nM 10 It has a high affinity for the receptor indicated by the low dissociation constant of 1 0 nanomolar nM 20 It has been reported that the effects of salvinorin A in mice are blocked by k opioid receptor antagonists 21 In addition salvinorin A has recently been found to act as a D2 receptor partial agonist with an affinity of 5 10 nM an intrinsic activity of 40 60 and an EC50 of 48 nM 22 This suggests that the D2 receptor may also play an important role in its effects 22 Salvinorin A shows atypical properties as an agonist of the KOR relative to other KOR agonists 23 For instance it is 40 fold less potent in promoting internalization receptor downregulation of the human KOR relative to the prototypical KOR agonist U 50488 citation needed Effect on intestinal motility edit Salvinorin A is capable of inhibiting excess intestinal motility e g diarrhea through its potent k opioid activating effects The mechanism of action for salvinorin A on ileal tissue has been described as prejunctional as it was able to modify electrically induced contractions but not those of exogenous acetylcholine 24 A pharmacologically important aspect of the contraction reducing properties of ingested salvinorin A on gut tissue is that it is only pharmacologically active on inflamed and not normal tissue thus reducing possible side effects 25 Solubility edit Salvinorin A is soluble in organic solvents such as ethanol and acetone but not especially so in water 26 Detection in urine edit Researchers found that humans who smoked 580 mg of the pure drug had urine salvinorin A concentrations of 2 4 10 9 µg L during the first hour the levels fell below the detection limit by 1 5 hours after smoking 27 Research editSalvinorin A has only been administered to humans in a few studies one showing that its effects peaked at about 2 minutes that its subjective effects may overlap with those of serotonergic psychedelics and that it temporarily impairs recall and recognition memory 4 Like most other agonists of kappa opioid receptors salvinorin A produces sedation psychotomimesis dysphoria anhedonia and depression 3 28 29 Salvinorin A has been screened for its possible use as a structural scaffold in medicinal chemistry in developing new drugs for treating psychiatric diseases 3 30 such as cocaine dependence 31 Synthesis edit nbsp Salvinorin A Biosynthesis edit The biogenic origin of salvinorin A synthesis has been elucidated using nuclear magnetic resonance and ESI MS analysis of incorporated precursors labeled with stable isotopes of carbon carbon 13 13C and hydrogen deuterium 2H It is biosynthesized via the 1 deoxy d xylulose 5 phosphate pathway rather than the classic mevalonate pathway consistent with the common plastidial localization of diterpenoid metabolism 32 Terpenoids are biosynthesized from two 5 carbon precursors isopentenyl diphosphate IPP and dimethylallyl diphosphate DMAPP The NMR and MS study by Zjawiony suggested that the biosynthesis of salvinorin A proceeds via the 1 deoxy d xylulose 5 phosphate pathway In the deoxyxylulose phosphate pathway D glyceraldehyde 3 phosphate and pyruvate the intermediates of the glycolysis are converted into 1 deoxy D xylulose 5 phosphate via decarboxylation Subsequent reduction with NADPH generates 2C methyl D erythritol 2 4 cyclodiphosphate via the intermediates 4 diphosphocytidyl 2 C methyl D erythritol and 4 diphosphocytidyl 2c methyl d erythritol 2 phosphate which then lead to IPP and DMAPP nbsp Synthesis of IPP and DMAPP via 1 deoxy d xylulose 5 phosphate pathway Subsequent addition of three 5 carbon IPP units to a single 5 carbon DMAPP unit generates the 20 carbon central precursor geranylgeranyl diphosphate GGPP Bicyclization of GGPP by the class II diterpene synthase ent clerodienyl diphosphate synthase SdCPS2 33 produces a labdanyl diphosphate carbocation which is subsequently rearranged through a sequence of 1 2 hydride and methyl shifts to form the ent clerodienyl diphosphate intermediate 34 SdCPS2 catalyzes the first committed reaction in the biosynthesis of salvinorin A by producing its characteristic clerodane scaffold A series of oxygenation acylation and methylation reactions is then required to complete the biosynthesis of salvinorin A 33 nbsp Biosynthesis of salvinorin A Similar to many plant derived psychoactive compounds salvinorin A is excreted via peltate glandular trichomes which reside external to the epidermis 35 36 Chemical synthesis edit A total asymmetric synthesis of salvinorin A which relies on a transannular Michael reaction cascade to construct the ring system was achieved as a 4 5 overall yield over 30 steps 37 then revised using 24 steps to yield salvinorin A in 0 15 yield 38 An approach to the trans decalin ring system of salvinorin A used an intramolecular Diels Alder reaction Tsuji allylation strategy 39 and a total synthesis of salvinorin A was achieved using the intramolecular Diels Alder Tsuji allylation approach combined with an asymmetric late stage addition of the furan moiety 40 Associated compounds editMain article Salvinorin Salvinorin A is one of several structurally related salvinorins found in the Salvia divinorum plant Salvinorin A is the only naturally occurring salvinorin that is known to be psychoactive 41 Salvinorin A can be synthesized from salvinorin B by acetylation and de acetylated salvinorin A becomes analog to salvinorin B 42 Research has produced a number of semi synthetic compounds Most derivatives are selective kappa opioid agonists as with salvinorin A although some are even more potent with the most potent compound salvinorin B ethoxymethyl ether being ten times stronger than salvinorin A Some derivatives such as herkinorin reduce kappa opioid action and instead act as mu opioid agonists 43 44 45 46 The synthetic derivative RB 64 is notable because of its functional selectivity and potency 47 Salvinorin B methoxymethyl ether is seven times more potent than salvinorin A at KOPr in GTP gS assays 48 Natural occurrence editSalvinorin A occurs naturally in several Salvia species S divinorum 0 89 mg g to 3 70 mg g 49 S recognita 212 9 mg g 50 S cryptantha 51 5 mg g 50 S glutinosa 38 9 mg g 50 Salvinorin B has been detected in S potentillifolia and S adenocaulon however these species do not contain a measureable amount of salvinorin A 50 Legal status editSee also Legal status of Salvia divinorum Salvinorin A is sometimes regulated together with its host Salvia divinorum due to its psychoactive and analgesic effects United States edit See also Legal status of Salvia divinorum in the United States Salvinorin A is not scheduled at the federal level in the United States 51 Its molecular structure is unlike any Schedule I or II drug so possession or sales is unlikely to be prosecuted under the Federal Analogue Act citation needed Florida edit Salvinorin A is a Schedule I controlled substance in the state of Florida making it illegal to buy sell or possess in Florida There is an exception however for any drug product approved by the United States Food and Drug Administration which contains salvinorin A or its isomers esters ethers salts and salts of isomers esters and ethers if the existence of such isomers esters ethers and salts is possible within the specific chemical designation 52 Australia edit Salvinorin A is considered a Schedule 9 prohibited substance in Australia under the Poisons Standard October 2015 53 A Schedule 9 substance is a substance which may be abused or misused the manufacture possession sale or use of which should be prohibited by law except when required for medical or scientific research or for analytical teaching or training purposes with approval of Commonwealth and or State or Territory Health Authorities 53 Sweden edit Sveriges riksdags health ministry Statens folkhalsoinstitut classified salvinorin A and Salvia divinorum as health hazard under the act Lagen om forbud mot vissa halsofarliga varor translated Act on the Prohibition of Certain Goods Dangerous to Health as of April 1 2006 in their regulation SFS 2006 167 listed as salvinorin A making it illegal to sell or possess 54 See also editPsychoactive drug List of entheogens Collybolide Nalfurafine Difelikefalin EnadolineReferences edit Anvisa 2023 07 24 RDC Nº 804 Listas de Substancias Entorpecentes Psicotropicas Precursoras e Outras sob Controle Especial Collegiate Board Resolution No 804 Lists of Narcotic Psychotropic Precursor and Other Substances under Special Control in Brazilian Portuguese Diario Oficial da Uniao published 2023 07 25 Archived from the original on 2023 08 27 Retrieved 2023 08 27 salvinorin A PubChem retrieved 2012 11 23 a b c d e Butelman ER Kreek MJ 2015 Salvinorin A a kappa opioid receptor agonist hallucinogen pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders Frontiers in Pharmacology 6 190 doi 10 3389 fphar 2015 00190 PMC 4561799 PMID 26441647 a b c MacLean KA Johnson MW Reissig CJ Prisinzano TE Griffiths RR March 2013 Dose related effects of salvinorin A in humans dissociative hallucinogenic and memory effects Psychopharmacology 226 2 381 392 doi 10 1007 s00213 012 2912 9 PMC 3581702 PMID 23135605 a b c Roth BL Baner K Westkaemper R Siebert D Rice KC Steinberg S et al September 2002 Salvinorin A a potent naturally occurring nonnitrogenous kappa opioid selective agonist Proceedings of the National Academy of Sciences of the United States of America 99 18 11934 11939 Bibcode 2002PNAS 9911934R doi 10 1073 pnas 182234399 JSTOR 3073142 PMC 129372 PMID 12192085 Ortega A Blount JF Manchard PD 1982 Salvinorin a new trans neoclerodane diterpene from Salvia divinorum Labiatae Journal of the Chemical Society Perkin Transactions 1 2505 8 doi 10 1039 P19820002505 Valdes III LJ 1983 The pharmacognosy ofSalvia divinorum Epling and Jativa M An Investigation of Ska Maria Pastora Mexico PhD thesis University of Michigan ProQuest 303280881 Valdes III LJ Butler WM Hatfield GM Paul AG Koreeda M 1984 Divinorin A a psychotropic terpenoid and divinorin B from the hallucinogenic Mexican mint Salvia divinorum Journal of Organic Chemistry 49 24 4716 20 doi 10 1021 jo00198a026 Valdes LJ Chang HM Visger DC Koreeda M November 2001 Salvinorin C a new neoclerodane diterpene from a bioactive fraction of the hallucinogenic Mexican mint Salvia divinorum Organic Letters 3 24 3935 3937 doi 10 1021 ol016820d PMID 11720573 a b c Prisinzano TE December 2005 Psychopharmacology of the hallucinogenic sage Salvia divinorum Life Sciences 78 5 527 531 doi 10 1016 j lfs 2005 09 008 PMID 16213533 a b Harding WW Schmidt M Tidgewell K Kannan P Holden KG Gilmour B et al January 2006 Synthetic studies of neoclerodane diterpenes from Salvia divinorum semisynthesis of salvinicins A and B and other chemical transformations of salvinorin A Journal of Natural Products 69 1 107 112 doi 10 1021 np050398i PMC 2544632 PMID 16441078 Salvinorin A pubchem ncbi nlm nih gov Johnson MW MacLean KA Caspers MJ Prisinzano TE Griffiths RR April 2016 Time course of pharmacokinetic and hormonal effects of inhaled high dose salvinorin A in humans Journal of Psychopharmacology 30 4 323 329 doi 10 1177 0269881116629125 PMC 5289219 PMID 26880225 a b Kivell B Uzelac Z Sundaramurthy S Rajamanickam J Ewald A Chefer V et al November 2014 Salvinorin A regulates dopamine transporter function via a kappa opioid receptor and ERK1 2 dependent mechanism Neuropharmacology 86 228 240 doi 10 1016 j neuropharm 2014 07 016 PMC 4188751 PMID 25107591 Siebert DJ June 1994 Salvia divinorum and salvinorin A new pharmacologic findings Journal of Ethnopharmacology 43 1 53 56 doi 10 1016 0378 8741 94 90116 3 PMID 7526076 Placzek MS Van de Bittner GC Wey HY Lukas SE Hooker JM December 2015 Immediate and Persistent Effects of Salvinorin A on the Kappa Opioid Receptor in Rodents Monitored In Vivo with PET Neuropsychopharmacology 40 13 2865 2872 doi 10 1038 npp 2015 159 PMC 4864638 PMID 26058662 Imanshahidi M Hosseinzadeh H June 2006 The pharmacological effects of Salvia species on the central nervous system Phytotherapy Research 20 6 427 437 doi 10 1002 ptr 1898 PMID 16619340 S2CID 35676076 However when smoked in a manner similar to free base cocaine the compound is effective in doses of 200 500 mg and produces visions that last from 30 minutes to an hour or two while doses over 2 mg are effective for much longer At doses greater than 500 mg the subject is often no longer aware of their surroundings and may enter an uncontrollable delirium This compound is the most potent naturally occurring hallucinogen thus far isolated Marushia R 2002 Salvia divinorum The Botany Ethnobotany Biochemistry and Future of a Mexican Mint PDF Ethnobotany Archived from the original PDF on October 7 2007 Retrieved 2006 12 23 Greiner T Burch NR Edelberg R February 1958 Psychopathology and psychophysiology of minimal LSD 25 dosage a preliminary dosage response spectrum A M A Archives of Neurology and Psychiatry 79 2 208 210 doi 10 1001 archneurpsyc 1958 02340020088016 PMID 13497365 Lee DY Ma Z Liu Chen LY Wang Y Chen Y Carlezon WA Cohen B October 2005 New neoclerodane diterpenoids isolated from the leaves of Salvia divinorum and their binding affinities for human kappa opioid receptors Bioorganic amp Medicinal Chemistry 13 19 5635 5639 doi 10 1016 j bmc 2005 05 054 PMID 16084728 Zhang Y Butelman ER Schlussman SD Ho A Kreek MJ May 2005 Effects of the plant derived hallucinogen salvinorin A on basal dopamine levels in the caudate putamen and in a conditioned place aversion assay in mice agonist actions at kappa opioid receptors Psychopharmacology 179 3 551 558 doi 10 1007 s00213 004 2087 0 PMID 15682306 S2CID 4533805 a b Seeman P Guan HC Hirbec H August 2009 Dopamine D2High receptors stimulated by phencyclidines lysergic acid diethylamide salvinorin A and modafinil Synapse 63 8 698 704 doi 10 1002 syn 20647 PMID 19391150 S2CID 17758902 Linda P Dwoskin 29 January 2014 Emerging Targets amp Therapeutics in the Treatment of Psychostimulant Abuse Elsevier Science pp 483 ISBN 978 0 12 420177 4 Capasso R Borrelli F Capasso F Siebert DJ Stewart DJ Zjawiony JK Izzo AA January 2006 The hallucinogenic herb Salvia divinorum and its active ingredient salvinorin A inhibit enteric cholinergic transmission in the guinea pig ileum Neurogastroenterology and Motility 18 1 69 75 doi 10 1111 j 1365 2982 2005 00725 x PMID 16371085 S2CID 4498185 Capasso R Borrelli F Zjawiony J Kutrzeba L Aviello G Sarnelli G et al February 2008 The hallucinogenic herb Salvia divinorum and its active ingredient salvinorin A reduce inflammation induced hypermotility in mice Neurogastroenterology and Motility 20 2 142 148 doi 10 1111 j 1365 2982 2007 00994 x PMID 17931335 S2CID 25081755 Salvia divinorum European Monitoring Centre for Drugs and Drug Addiction Retrieved 4 September 2014 Salvinorin A is unstable in basic solutions and is soluble in conventional organic solvents including acetone acetonitrile chloroform dimethyl sulfoxide and methanol but is essentially insoluble in hexane and water Pichini S Abanades S Farre M Pellegrini M Marchei E Pacifici R et al 30 June 2005 Quantification of the plant derived hallucinogen Salvinorin A in conventional and non conventional biological fluids by gas chromatography mass spectrometry after Salvia divinorum smoking Rapid Communications in Mass Spectrometry 19 12 1649 1656 Bibcode 2005RCMS 19 1649P doi 10 1002 rcm 1970 PMID 15915477 Mott PL 2 December 2011 A Literature Review on the Status and Effects of Salvia Divinorum on Cognitive Affective and Behavioral Functioning Universal Publishers pp 27 ISBN 978 1 61233 777 7 Biller J 2008 The Interface of Neurology amp Internal Medicine Lippincott Williams amp Wilkins pp 681 ISBN 978 0 7817 7906 7 Orton E Liu R 2014 Salvinorin A A Mini Review of Physical and Chemical Properties Affecting Its Translation from Research to Clinical Applications in Humans Translational Perioperative and Pain Medicine 1 1 9 11 PMC 4208627 PMID 25346937 Kivell BM Ewald AW Prisinzano TE 2014 Salvinorin a Analogs and Other Kappa Opioid Receptor Compounds as Treatments for Cocaine Abuse Salvinorin A analogs and other k opioid receptor compounds as treatments for cocaine abuse Advances in Pharmacology Vol 69 pp 481 511 doi 10 1016 B978 0 12 420118 7 00012 3 ISBN 9780124201187 PMC 4128345 PMID 24484985 Kutrzeba L Dayan FE Howell J Feng J Giner JL Zjawiony JK July 2007 Biosynthesis of salvinorin A proceeds via the deoxyxylulose phosphate pathway Phytochemistry 68 14 1872 1881 Bibcode 2007PChem 68 1872K doi 10 1016 j phytochem 2007 04 034 PMC 2065853 PMID 17574635 a b Salvia divinorum kolavenyl diphosphate synthase CPS2 mRNA complete cds December 11 2016 via NCBI Nucleotide Pelot KA Mitchell R Kwon M Hagelthorn LM Wardman JF Chiang A et al March 2017 Biosynthesis of the psychotropic plant diterpene salvinorin A Discovery and characterization of the Salvia divinorum clerodienyl diphosphate synthase The Plant Journal 89 5 885 897 doi 10 1111 tpj 13427 PMID 27865008 Siebert DJ June 2004 Localization of salvinorin A and related compounds in glandular trichomes of the psychoactive sage Salvia divinorum Annals of Botany 93 6 763 771 doi 10 1093 aob mch089 JSTOR 43576030 PMC 4242294 PMID 15087301 Kunkel D 2007 Leaf glandular trichome Salvia divinorum Dennis Kunkel Microscopy Inc Retrieved 2022 04 04 Scheerer JR Lawrence JF Wang GC Evans DA July 2007 Asymmetric synthesis of salvinorin A a potent kappa opioid receptor agonist Journal of the American Chemical Society 129 29 8968 8969 doi 10 1021 ja073590a PMID 17602636 Nozawa M Suka Y Hoshi T Suzuki T Hagiwara H April 2008 Total synthesis of the hallucinogenic neoclerodane diterpenoid salvinorin A Organic Letters 10 7 1365 1368 doi 10 1021 ol800101v PMID 18311991 Burns AC Forsyth CJ January 2008 Intramolecular Diels Alder Tsuji allylation assembly of the functionalized trans decalin of salvinorin A Organic Letters 10 1 97 100 doi 10 1021 ol7024058 PMID 18062692 Line NJ Burns AC Butler SC Casbohm J Forsyth CJ December 2016 Total Synthesis of Salvinorin A Chemistry A European Journal 22 50 17983 17986 doi 10 1002 chem 201604853 PMID 27758012 Munro TA Rizzacasa MA May 2003 Salvinorins D F new neoclerodane diterpenoids from Salvia divinorum and an improved method for the isolation of salvinorin A Journal of Natural Products 66 5 703 705 doi 10 1021 np0205699 PMID 12762813 Lee DY Karnati VV He M Liu Chen LY Kondaveti L Ma Z et al August 2005 Synthesis and in vitro pharmacological studies of new C 2 modified salvinorin A analogues Bioorganic amp Medicinal Chemistry Letters 15 16 3744 3747 doi 10 1016 j bmcl 2005 05 048 PMID 15993589 Munro TA Duncan KK Xu W Wang Y Liu Chen LY Carlezon WA et al February 2008 Standard protecting groups create potent and selective kappa opioids salvinorin B alkoxymethyl ethers Bioorganic amp Medicinal Chemistry 16 3 1279 1286 doi 10 1016 j bmc 2007 10 067 PMC 2568987 PMID 17981041 Holden KG Tidgewell K Marquam A Rothman RB Navarro H Prisinzano TE November 2007 Synthetic studies of neoclerodane diterpenes from Salvia divinorum exploration of the 1 position Bioorganic amp Medicinal Chemistry Letters 17 22 6111 6115 doi 10 1016 j bmcl 2007 09 050 PMC 2111044 PMID 17904842 Lee DY He M Liu Chen LY Wang Y Li JG Xu W et al November 2006 Synthesis and in vitro pharmacological studies of new C 4 modified salvinorin A analogues Bioorganic amp Medicinal Chemistry Letters 16 21 5498 5502 doi 10 1016 j bmcl 2006 08 051 PMID 16945525 Beguin C Richards MR Li JG Wang Y Xu W Liu Chen LY et al September 2006 Synthesis and in vitro evaluation of salvinorin A analogues effect of configuration at C 2 and substitution at C 18 Bioorganic amp Medicinal Chemistry Letters 16 17 4679 4685 doi 10 1016 j bmcl 2006 05 093 PMID 16777411 White KL Robinson JE Zhu H DiBerto JF Polepally PR Zjawiony JK et al January 2015 The G protein biased k opioid receptor agonist RB 64 is analgesic with a unique spectrum of activities in vivo The Journal of Pharmacology and Experimental Therapeutics 352 1 98 109 doi 10 1124 jpet 114 216820 PMC 4279099 PMID 25320048 Wang Y Chen Y Xu W Lee DY Ma Z Rawls SM et al March 2008 2 Methoxymethyl salvinorin B is a potent kappa opioid receptor agonist with longer lasting action in vivo than salvinorin A The Journal of Pharmacology and Experimental Therapeutics 324 3 1073 1083 doi 10 1124 jpet 107 132142 PMC 2519046 PMID 18089845 Brito da Costa AM Dias da Silva D Gomes NG Dinis Oliveira RJ Madureira Carvalho A February 2021 Pharmacokinetics and Pharmacodynamics of Salvinorin A and Salvia divinorum Clinical and Forensic Aspects Pharmaceuticals 14 2 116 doi 10 3390 ph14020116 PMC 7913753 PMID 33546518 a b c d Hatipoglu SD Yalcinkaya B Akgoz M Ozturk T Goren AC Topcu G November 2017 Screening of Hallucinogenic Compounds and Genomic Characterisation of 40 Anatolian Salvia Species Phytochemical Analysis 28 6 541 549 Bibcode 2017PChAn 28 541H doi 10 1002 pca 2703 PMID 28722248 21 CFR Schedules of Controlled Substances 1308 11 Schedule I Archived from the original on 2009 08 27 Retrieved 2014 12 18 Statutes amp Constitution View Statutes Online Sunshine leg state fl us a b Poisons Standard The Australian Government October 2015 Forordning om andring i forordningen 1999 58 om forbud mot vissa halsofarliga varor Ordinance amending the ordinance 1999 58 on the prohibition of certain dangerous goods PDF in Swedish Svensk forfattningssamling 2006 Archived from the original PDF on 2013 09 29 Retrieved 2013 09 25 Further reading editBaselt RC 2008 Disposition of Toxic Drugs and Chemicals in Man 8th ed Foster City CA Biomedical Publications pp 1405 6 ISBN 978 0 9626523 7 0 Retrieved from https en wikipedia org w index php title Salvinorin A amp oldid 1213995966, wikipedia, wiki, book, books, library,

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