Salvinorin A

Chembox new
ImageFile=Salvinorin-A structure.pngImageSize=150px
ImageFile2=Salvinorin A-sticks.pngImageSize2=130px
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Section1= Chembox Identifiers
CASNo=83729-01-5
PubChem=128563
SMILES=CC(=O)OC1CC(C2(CCC3C(=O)OC (CC3(C2C1=O)C)C4=COC=C4)C)C(=O)OC
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
MeSHName=Salvinorin+A
Section2= Chembox Properties
Formula=C₂₃H₂₈O₈
MolarMass=432.464
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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 quantitative 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.cite journal
author=Roth BL, Baner K, Westkaemper R, "et al"
title=Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist
journal=Proc. Natl. Acad. Sci. U.S.A.
volume=99
issue=18
pages=11934–9
year=2002
pmid=12192085
doi=10.1073/pnas.182234399]

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.

Chemistry

Salvinorin A is a "trans"-neoclerodane diterpenoid, chemical formula C₂₃H₂₈O₈.cite journal
author=Prisinzano TE
title=Psychopharmacology of the hallucinogenic sage Salvia divinorum
journal=Life Sci.
volume=78
issue=5
pages=527–31
year=2005
pmid=16213533
doi=10.1016/j.lfs.2005.09.008] Unlike other known opioid-receptor ligands, salvinorin A is not an alkaloid — it does not contain a basic nitrogen atom.cite journal
author=Harding WW, Schmidt M, Tidgewell K, "et al"
title=Synthetic studies of neoclerodane diterpenes from Salvia divinorum: semisynthesis of salvinicins A and B and other chemical transformations of salvinorin A
journal=J. Nat. Prod.
volume=69
issue=1
pages=107–12
year=2006
pmid=16441078
doi=10.1021/np050398i] Salvinorin A has no actions at the 5-HT_2A serotonin receptor, the principal molecular target responsible for the actions of 'classical' psychedelics such as LSD and mescaline.

Salvinorin A is one of the most potent naturally occurring psychoactive compounds known.cite journal
author=Imanshahidi M, Hosseinzadeh H
title=The pharmacological effects of Salvia species on the central nervous system
journal=Phytother Res
volume=20
issue=6
pages=427–37
year=2006
pmid=16619340
doi=10.1002/ptr.1898] It is active at doses as low as 200 µg.Citation
last=Marushia
first=Robin
year=2002
title="Salvia divinorum": The Botany, Ethnobotany, Biochemistry and Future of a Mexican Mint
journal=Ethnobotany
url=http://www.cyjack.com/Cognition/Salvia.pdf
accessdate=2006-12-23
format=dead link|date=June 2008 – ^{[http://scholar.google.co.uk/scholar?hl=en&lr=&q=author%3AMarushia+intitle%3A%27%27Salvia+divinorum%27%27%3A+The+Botany%2C+Ethnobotany%2C+Biochemistry+and+Future+of+a+Mexican+Mint&as_publication=Ethnobotany&as_ylo=2002&as_yhi=2002&btnG=Search Scholar search]} ] Recent research has shown that salvinorin A is a potent and selective κ (kappa) opioid receptor agonist. It has been reported that the effects of salvinorin A in mice are blocked by kappa opioid receptor antagonists.cite journal
author=Zhang Y, Butelman ER, Schlussman SD, Ho A, Kreek MJ
title=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
journal=Psychopharmacology (Berl.)
volume=179
issue=3
pages=551–8
year=2005
pmid=15682306
doi=10.1007/s00213-004-2087-0] 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.cite journal
author=Mowry M, Mosher M, Briner W
title=Acute physiologic and chronic histologic changes in rats and mice exposed to the unique hallucinogen salvinorin A
journal=J Psychoactive Drugs
volume=35
issue=3
pages=379–82
year=2003
pmid=14621136
url=http://www.sagewisdom.org/mowryetal.pdf
doi=]

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.cite journal
author=Bigham AK, Munro TA, Rizzacasa MA, Robins-Browne RM
title=Divinatorins A-C, new neoclerodane diterpenoids from the controlled sage Salvia divinorum
journal=J. Nat. Prod.
volume=66
issue=9
pages=1242–4
year=2003
pmid=14510607
doi=10.1021/np030313i]

alvinorin 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. [cite web
url = http://sagewisdom.org/faq.html
title = The "Salvia divinorum" FAQ
accessdate = 2007-07-05
accessdaymonth =
accessmonthday =
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author =
last = Siebert
first = Daniel
authorlink =
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date =
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publisher = The Salvia divinorum Research and Information Center
pages =
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quote = ] 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.

alvinorin A synthesis

A significant attempt at the synthesis of salvinorin A has been published by a group at RMIT University, adopting a convergentsynthesis of a functionalized cyclohexanone with a α,β-unsaturated lactone.cite journal
author= Lingham AR, Hügel HM, Rook TJ
title=Studies Towards the Synthesis of Salvinorin A
journal=Aust. J. Chem.
volume=59
issue=5
pages=340–348
year=2006
doi=10.1071/CH05338]

A total asymmetric synthesis of salvinorin A was achieved recently by Evans and co-workers.cite journal
author=Scheerer JR, Lawrence JF, Wang GC, Evans DA
title=Asymmetric synthesis of salvinorin A, a potent kappa opioid receptor agonist
journal=J. Am. Chem. Soc.
volume=129
issue=29
pages=8968–9
year=2007
pmid=17602636
doi=10.1021/ja073590a]

alvinorins 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.cite journal
author=Munro TA, Rizzacasa MA
title=Salvinorins D-F, new neoclerodane diterpenoids from Salvia divinorum, and an improved method for the isolation of salvinorin A
journal=J. Nat. Prod.
volume=66
issue=5
pages=703–5
year=2003
pmid=12762813
doi=10.1021/np0205699]

ee also

* Dissociative drug
* Psychoactive drug
* Psychedelic plants
* Salvia divinorum
* List of Entheogens
* Enadoline
* Herkinorin

References

Further reading

*Citation
last1=Chavkin
first1=Charles
first2=Sumit
last2=Sud
first3=Wenzhen
last3=Jin
first4=Jeremy
last4=Stewart
first5=Jordan K.
last5=Zjawiony
first6=Daniel J.
last6=Siebert
first7=Beth Ann
last7=Toth
first8=Sandra J.
last8=Hufeisen
first9=Bryan L.
last9=Roth
year=2004
date=Jan 2004
title=Salvinorin A, an Active Component of the Hallucinogenic Sage "Salvia divinorum" Is a Highly Efficacious κ-Opioid Receptor Agonist: Structural and Functional Considerations
journal=Journal of Pharmacology And Experimental Therapeutics
volume=308
issue=3
pages=1197–1203
url=http://jpet.aspetjournals.org/cgi/content/abstract/308/3/1197
doi=10.1124/jpet.103.059394
accessdate=2007-03-24
pmid=14718611.
*Citation
last1=Munro
first1=Thomas A.
first2=Mark A.
last2=Rizzacasa
first3=Bryan L.
last3=Roth
first4=Beth A.
last4=Toth
first5=Feng
last5=Yan
year=2005
date=Jan 2005
title=Studies toward the pharmacophore of salvinorin A, a potent kappa opioid receptor agonist
journal=Journal of Medicinal Chemistry
volume=48
issue=2
pages=345–348
url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=Display&DB=pubmed
pmid=15658846
accessdate=2007-03-24
doi=10.1021/jm049438q.

External links

* [http://www.sagewisdom.org/ The "Salvia divinorum" Research and Information Center (Daniel Siebert)]
* [http://www.erowid.org/plants/salvia/salvia.shtml Erowid "Salvia divinorum" vault]
* [http://leda.lycaeum.org/?ID=156 Lycaeum Salvinorin A]
* [http://www.tryptamind.com/salvinorin.html Tryptamind Salvinorin A] Downloadable salvinorin extraction photos.