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Salvinorin A



Salvinorin A
Identifiers
CAS number 83729-01-5
PubChem 128563
MeSH Salvinorin+A
SMILES CC(=O)OC1CC(C2(CCC3C(=O)OC (CC3(C2C1=O)C)C4=COC=C4)C)C(=O)OC
InChI InChI=1/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
Properties
Molecular formula C23H28O8
Molar mass 432.464
Except where noted otherwise, data are given for
materials in their standard state
(at 25 °C, 100 kPa)

Infobox disclaimer and references

Salvinorin A is the main active psychotropic molecule in Salvia divinorum, a Mexican plant which has a long history of use as an entheogen by indigenous Mazatec shamans. Salvinorin A is a hallucinogenic compound with dissociative effects. It is structurally quite distinct from other naturally occurring hallucinogens such as N,N-dimethyltryptamine, psilocybin, and mescaline and from synthetic hallucinogens such as lysergic acid diethylamide (LSD), and ketamine. Salvinorin A has been reported to be the most potent naturally occurring psychoactive drug known to date, with an effective dose in humans in the 200- to 1,000-µg range when smoked. In that way Salvinorin A's qualitative potency may be compared with LSD, though it is otherwise dissimilar, having quite different effects and timeframes. 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.[1]

Salvinorin A is found together 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. Salvinorin A was isolated in 1982 by Alfredo Ortega in Mexico. Its pharmacological mechanism was elucidated in the laboratory of Bryan L. Roth.

Additional recommended knowledge

Contents

Chemistry

Salvinorin A is a trans-neoclerodane diterpenoid, chemical formula C23H28O8.[2] Unlike other known opioid-receptor ligands, salvinorin A is not an alkaloid — it does not contain a basic nitrogen atom.[3] Salvinorin A has no actions at the 5-HT2A serotonin receptor, the principal molecular target responsible for the actions of 'classical' psychedelics such as LSD and mescaline.[3]

Salvinorin A is the most potent naturally-occurring psychoactive compound known.[4] It is active at doses as low as 200 µg.[2][4][5] Recent research has shown that salvinorin A is a potent and selective κ (kappa) opioid receptor agonist.[2] It has been reported that the effects of salvinorin A in mice are blocked by kappa opioid receptor antagonists.[6] This makes it unlikely that another mechanism contributes independently to the compound’s observed effects in mice. Salvinorin A is unique in that it is the only naturally occurring substance known to induce a visionary state via this mode of action (although there are a few other synthetic kappa opioid agonists, such as enadoline, which show similar hallucinatory and dissociative effects).

Salvinorin's potency should not be confused with toxicity. Rodents chronically exposed to dosages many times greater than those to which humans are exposed did not show signs of organ damage.[7]

Many other terpenoids have been isolated from S. divinorum, including other salvinorins and related compounds named divinatorins and salvinicins. None of these compounds has shown significant (sub-micromolar) affinity at the kappa opioid receptor, and there is no evidence that they contribute to the plant's psychoactivity.[8][9]

Salvinorin extraction

 

According to Daniel Siebert in his Salvia Divinorum FAQ, the extraction and purification of salvinorin A should only be attempted by qualified researchers with experience in chemistry and the proper laboratory equipment, particularly as measurement of safe dosages is difficult.[10] Though salvinorin A can be vaporized and inhaled, the overwhelming potency of even minute quantities of salvinorin A makes a sophisticated analytical balance essential for measuring a safe dose. However, rather than trying to obtain pure salvinorin crystals, many less technically qualified choose to produce a concentrate, starting from a given amount of leaf mass, for the purpose of making enhanced strength leaf. The resulting wax/crystal mix from such partial extraction is then returned to a smaller amount of leaf or a substrate. By choosing the amount of leaf or substrate to deposit the mix onto, the dosage is controlled by the ratio of substrate to original leaf mass.

Salvinorin A synthesis

A significant attempt at the synthesis of salvinorin A has been published by a group at RMIT University, adopting a convergent synthesis of a functionalized cyclohexanone with a α,β-unsaturated lactone.[11]

A total asymmetric synthesis of salvinorin A was achieved recently by Evans and co-workers.[12]

Salvinorins A - F

Salvinorin A is one of several structurally related salvinorins. Salvinorin A can be synthesized from the inactive salvinorin B by acetylation. The des-acetylated analog salvinorin B is devoid of human activity. It was speculated that salvinorin C might be even more potent than salvinorin A, but human tests and receptor binding assays could not confirm this. Salvinorin A seems to be the only active naturally occurring salvinorin.[9]

 
Salvinorins A - F: General formulas
   
Salvinorins A - F
NameR1StructureActivity
Salvinorin A-OCOCH3-1active
Salvinorin B-OH-1inactive
Salvinorin C-OCOCH3-OCOCH32inactive
Salvinorin D-OH-OCOCH32inactive
Salvinorin E-OCOCH3-OH2inactive
Salvinorin F-H-OH2unknown

See also

References

  1. ^ Roth BL, Baner K, Westkaemper R, et al (2002). "Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist". Proc. Natl. Acad. Sci. U.S.A. 99 (18): 11934–9. doi:10.1073/pnas.182234399. PMID 12192085.
  2. ^ a b c Prisinzano TE (2005). "Psychopharmacology of the hallucinogenic sage Salvia divinorum". Life Sci. 78 (5): 527–31. doi:10.1016/j.lfs.2005.09.008. PMID 16213533.
  3. ^ a b Harding WW, Schmidt M, Tidgewell K, et al (2006). "Synthetic studies of neoclerodane diterpenes from Salvia divinorum: semisynthesis of salvinicins A and B and other chemical transformations of salvinorin A". J. Nat. Prod. 69 (1): 107–12. doi:10.1021/np050398i. PMID 16441078.
  4. ^ a b Imanshahidi M, Hosseinzadeh H (2006). "The pharmacological effects of Salvia species on the central nervous system". Phytother Res 20 (6): 427–37. doi:10.1002/ptr.1898. PMID 16619340.
  5. ^ Marushia, Robin (2002), " ", Ethnobotany, . Retrieved on 2006-12-23
  6. ^ Zhang Y, Butelman ER, Schlussman SD, Ho A, Kreek MJ (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 (Berl.) 179 (3): 551–8. doi:10.1007/s00213-004-2087-0. PMID 15682306.
  7. ^ Mowry M, Mosher M, Briner W (2003). "Acute physiologic and chronic histologic changes in rats and mice exposed to the unique hallucinogen salvinorin A". J Psychoactive Drugs 35 (3): 379–82. PMID 14621136.
  8. ^ Bigham AK, Munro TA, Rizzacasa MA, Robins-Browne RM (2003). "Divinatorins A-C, new neoclerodane diterpenoids from the controlled sage Salvia divinorum". J. Nat. Prod. 66 (9): 1242–4. doi:10.1021/np030313i. PMID 14510607.
  9. ^ a b Munro TA, Rizzacasa MA (2003). "Salvinorins D-F, new neoclerodane diterpenoids from Salvia divinorum, and an improved method for the isolation of salvinorin A". J. Nat. Prod. 66 (5): 703–5. doi:10.1021/np0205699. PMID 12762813.
  10. ^ Siebert, Daniel. The Salvia divinorum FAQ. The Salvia divinorum Research and Information Center. Retrieved on 2007-07-05.
  11. ^ Lingham AR, Hügel HM, Rook TJ (2006). "Studies Towards the Synthesis of Salvinorin A". Aust. J. Chem. 59 (5): 340-348. doi:10.1071/CH05338.
  12. ^ Scheerer JR, Lawrence JF, Wang GC, Evans DA (2007). "Asymmetric synthesis of salvinorin A, a potent kappa opioid receptor agonist". J. Am. Chem. Soc. 129 (29): 8968–9. doi:10.1021/ja073590a. PMID 17602636.

Further reading

  • Chavkin, Charles; Sud, Sumit & Jin, Wenzhen et al. (Jan 2004), " ", Journal of Pharmacology And Experimental Therapeutics 308 (3): 1197-1203, doi:10.1124/jpet.103.059394, . Retrieved on 2007-03-24.
  • Munro, Thomas A.; Rizzacasa, Mark A. & Roth, Bryan L. et al. (Jan 2005), " ", Journal of Medicinal Chemistry 48 (2): 345–348, PMID 15658846, . Retrieved on 2007-03-24.
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Salvinorin_A". A list of authors is available in Wikipedia.
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