Salvinorin A
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| Salvinorin A | |
|---|---|
| Chemical name |
(2S,4aR,6aR,7R,9S,10aS,10bR)-methyl |
| Chemical formula | C23H28O8 |
| Molecular mass | 432.46 g/mol |
| Melting point | 238 - 240 °C |
| CAS number | 83729-01-5 |
| SMILES | O=C1[C@@]2([H])[C@](CC[C@]3([H])[C@] 2(C)C[C@](C4=COC=C4)([H])OC3=O)(C) [C@H]([C@](OC)=O)C[C@@H]1OC(C)=O |
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 independently in 1982 by Alfredo Ortega in Mexico and in 1984 by Leander J. Valdes III in the USA. Its pharmacological mechanism was elucidated in the laboratory of Bryan L. Roth.
Contents |
[edit] 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 hallucinogens.[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 effects. Salvinorin A is unique in that it is the only naturally occurring substance known to induce a visionary state via this mode of action.
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.
[edit] 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. 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.
[edit] 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.[8]
[edit] 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.
Structure 1:
Salvinorin A and B |
Structure 2:
Salvinorin C - F |
| Name | R1 | R2 | Structure | Activity |
|---|---|---|---|---|
| Salvinorin A | -OCOCH3 | - | 1 | active |
| Salvinorin B | -OH | - | 1 | inactive |
| Salvinorin C | -OCOCH3 | -OCOCH3 | 2 | inactive |
| Salvinorin D | -OH | -OCOCH3 | 2 | inactive |
| Salvinorin E | -OCOCH3 | -OH | 2 | inactive |
| Salvinorin F | -H | -OH | 2 | unknown |
[edit] See also
[edit] References
- ^ Roth et al. 2002, p. intro.
- ^ a b c Prisinzano 2005, p. 528.
- ^ a b Harding, Schmidt & Tidgewell 2006, p. 107.
- ^ a b Imanshahidi & Hosseinzadeh 2006, p. 431.
- ^ Marushia 2002, p. 11.
- ^ Zhang et al. 2005, p. abstract.
- ^ Mowry, Mosher & Briner 2003, p. 382.
- ^ Lingham, Hügel & Rook 2006, p. 340.
[edit] Citations
- Harding, Wayne W.; Matthew Schmidt & Kevin Tidgewell (Jan 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, PMID 16441078.
- Imanshahidi, Mohsen & Hossein Hosseinzadeh (Apr 2006), "The Pharmacological Effects of Salvia species on the Central Nervous System", Phytotherapy Research 20: 427–437, DOI:10.1002/ptr.1898.
- Lingham, Anthony; Hügel Helmut & Rook Trevor (Jul 2006), "Studies Towards the Synthesis of Salvinorin A", Australian Journal of Chemistry 59: 340–348, DOI:10.1071/CH05338.
- Marushia, Robin (2002), "Salvia divinorum: The Botany, Ethnobotany, Biochemistry and Future of a Mexican Mint", Ethnobotany.
- Mowry, Mark; Michael Mosher & Wayne Briner (Jul 2003), "Acute Physiologic and Chronic Histologic Changes in Rats and Mice Exposed to the Unique Hallucinogen Salvinorin A", Journal of Psychoactive Drugs 35: 379–382, PMID 14621136.
- Prisinzano, Thomas E. (Oct 2005), "Psychopharmacology of the hallucinogenic sage Salvia divinorum", Life Sciences 78 (5): 527–531, DOI:10.1016/j.lfs.2005.09.008.
- Roth, Bryan L.; Karen Baner & Richard Westkaemper et al. (Sep 2002), "Salvinorin A: A potent naturally occurring nonnitrogenous kappa к opioid selective agonist", PNAS 99 (18): 11934–11939, PMID 12192085.
- Zhang, Yong; Eduardo R. Butelman & Stefan D. Schlussman et al. (Jan 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, Springer Berlin / Heidelberg, DOI:10.1007/s00213-004-2087-0.
[edit] Further citations
- Chavkin, Charles; Sumit Sud & Wenzhen Jin et al. (Jan 2004), "Salvinorin A, an Active Component of the Hallucinogenic Sage Salvia divinorum Is a Highly Efficacious κ-Opioid Receptor Agonist: Structural and Functional Considerations", Journal of Pharmacology And Experimental Therapeutics 308 (3): 1197-1203, DOI:10.1124/jpet.103.059394.
- Munro, Thomas A.; Mark A. Rizzacasa & Bryan L. Roth et al. (Jan 2005), "Studies toward the pharmacophore of salvinorin A, a potent kappa opioid receptor agonist", Journal of Medicinal Chemistry 48 (2): 345–348, PMID 15658846.
[edit] External links
- The Salvia divinorum Research and Information Center (Daniel Siebert)
- Erowid Salvia divinorum vault
- Lycaeum Salvinorin A
- Photographs of Crystalline Salvinorin-A and .PDF Extraction Articles.
- Tryptamind Salvinorin A Downloadable salvinorin extraction photos.
Dextromethorphan, Ketamine, Nitrous oxide, PCP, Salvinorin A, Tiletamine, Memantine
