Salvinorins are a group of natural chemical compounds and their

structural analog A structural analog (analogue in modern traditional English; Commonwealth English), also known as a chemical analog or simply an analog, is a compound having a structure similar to that of another compound, but differing from it in respect to a ce ...

s. Several salvinorins have been isolated from ''

Salvia divinorum ''Salvia divinorum'' (Latin: "sage of the diviners"; also called ska maría pastora, seer's sage, yerba de la pastora, magic mint or simply salvia) is a plant species with transient psychoactive properties when its leaves are consumed by che ...

''. They are classified as

diterpenoid Diterpenes are a class of chemical compounds composed of four isoprene units, often with the molecular formula C20H32. They are biosynthesized by plants, animals and fungi via the HMG-CoA reductase pathway, with geranylgeranyl pyrophosphate being ...

furanolactone A furanolactone is a heterocyclic chemical compound that contains both a lactone and a furan ring structure. Examples include: * The salvinorins, including the hallucinogenic compound salvinorin A * Columbin, a bitter diterpenoid from '' Calumb ...

Salvinorin A Salvinorin A is the main active psychotropic molecule in '' Salvia divinorum''. Salvinorin A is considered a dissociative hallucinogen. It is structurally distinct from other naturally occurring hallucinogens (such as DMT, psilocybin, and ...

is a hallucinogen with dissociative effects. Several salvinorins have been isolated and characterized.

Occurrence

Originally isolated from ''S. divinorum'', salvinorins are also detected in smaller amounts in: * '' Salvia recognita'' (salvinorin A, 212.9 μg/g) * ''

Salvia absconditiflora ''Salvia absconditiflora'' is a perennial plant species of the family Lamiaceae. It is endemic to Turkey. It contains Salvinorin A at a concentration of 51.5 Microgram, micrograms per gram of plant material. References

Salvia, abscondit ...

'' (salvinorin A at 51.5 μg/g, and salvinorin B at 402.2 μg/g) * ''

Salvia glutinosa ''Salvia glutinosa'', the glutinous sage, sticky sage, Jupiter's sage, or Jupiter's distaff, is a herbaceous perennial plant belonging to the family Lamiaceae. Description ''Salvia glutinosa'' grows to approximately tall.Pignatti S. - Flora d' ...

'' (salvinorin A, 38.9 μg/g) * '' Salvia potentillifolia'' (salvinorin B, 2352.0 μg/g) * '' Salvia adenocaulon'' (salvinorin B, 768.8 μg/g) For comparison, the amount of salvinorin A in ''S. divinorum'' ranges from 0.89 to 3.70 mg/g. All fractions reported are based on dry mass. Interestingly, the above reported species are not very closely related to ''S. divinorum''.

Associated compounds

In search for useful biological activity, several synthetic and

semi-synthetic Semisynthesis, or partial chemical synthesis, is a type of chemical synthesis that uses chemical compounds isolated from natural sources (such as microbial cell cultures or plant material) as the starting materials to produce novel compounds with ...

analogs have been prepared for study. Semi-synthetic analogs include

salvinorin B ethoxymethyl ether Salvinorin B methoxymethyl ether (2-''O''-methoxymethylsalvinorin B) is a semi-synthetic analogue of the natural product salvinorin A used in scientific research. It has a longer duration of action of around 2–3 hours, compared to less than 30 ...

and salvinorin B methoxymethyl ether. Fully synthetic analogs include

herkinorin Herkinorin is an opioid analgesic that is an analog (chemistry), analogue of the natural product salvinorin A. It was discovered in 2005 during structure-activity relationship studies into neoclerodane diterpenes, the family of chemical compounds ...

. Several derivates can be conveniently made from salvinorin B. Most derivatives are selective kappa opioid

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

s as with salvinorin A, although some are even more potent, with the most potent compound 2-ethoxymethyl salvinorin B being ten times stronger than salvinorin A. Some derivatives, such as

, reduce kappa opioid action and instead act as mu opioid agonists. 22-Thiocyanato-salvinorin A is notable because of its

functional selectivity Functional selectivity (or “agonist trafficking”, “biased agonism”, “biased signaling”, "ligand bias" and “differential engagement”) is the ligand-dependent selectivity for certain signal transduction pathways relative to a referen ...

. 2-Methoxymethyl Salvinorin B is seven times more potent than Salvinorin A at KOPr in GTP-γS assays. Many other terpenoids have been isolated from ''Salvia divinorum'', including classes named divinatorins and salvinicins. None of these compounds have shown significant (sub-micromolar) affinity at the kappa-opioid receptor, and there is no evidence that they contribute to the plant's psychoactivity.

References

{{Reflist, colwidth=30em, refs= {{cite journal , author1=Béguin C , author2=Richards MR , author3=Li JG , author4=Wang Y , author5=Xu W , author6=Liu-Chen LY , author7=Carlezon WA , author8=Cohen BM , title=Synthesis and in vitro evaluation of salvinorin A analogues: effect of configuration at C(2) and substitution at C(18) , journal=Bioorganic & Medicinal Chemistry Letters , volume=16 , issue=17 , pages=4679–85 , year=2006 , pmid=16777411 , doi=10.1016/j.bmcl.2006.05.093 {{cite journal , author1=Bigham AK , author2=Munro TA , author3=Rizzacasa MA , author4=Robins-Browne RM , title=Divinatorins A-C, new neoclerodane diterpenoids from the controlled sage ''Salvia divinorum'' , journal=Journal of Natural Products , volume=66 , issue=9 , pages=1242–4 , year=2003 , pmid=14510607 , doi=10.1021/np030313i, citeseerx=10.1.1.693.6690 {{cite journal , author1=Holden KG , author2=Tidgewell K , author3=Marquam A , author4=Rothman RB , author5=Navarro H , author6=Prisinzano TE , title=Synthetic studies of neoclerodane diterpenes from ''Salvia divinorum'': exploration of the 1-position , journal=Bioorganic & Medicinal Chemistry Letters , year=2007 , volume=17 , issue=22 , pages=6111–5 , pmid=17904842 , doi=10.1016/j.bmcl.2007.09.050 , pmc=2111044 {{cite journal , author1=Lee DY , author2=He M , author3=Liu-Chen LY , author4=Wang Y , author5=Li JG , author6=Xu W , author7=Ma Z , author8=Carlezon WA , author9=Cohen B , title=Synthesis and in vitro pharmacological studies of new C(4)-modified salvinorin A analogues , journal=Bioorganic & Medicinal Chemistry Letters , volume=16 , issue=21 , pages=5498–502 , year=2006 , pmid=16945525 , doi=10.1016/j.bmcl.2006.08.051 {{cite journal , author1=Munro TA , author2=Rizzacasa MA , title=Salvinorins D-F, new neoclerodane diterpenoids from ''Salvia divinorum'', and an improved method for the isolation of salvinorin A , journal=Journal of Natural Products , volume=66 , issue=5 , pages=703–5 , year=2003 , pmid=12762813 , doi=10.1021/np0205699 {{cite journal , author1=Munro TA , author2=Duncan KK , author3=Xu W , author4=Wang Y , author5=Liu-Chen LY , author6=Carlezon WA , author7=Cohen BM , author8=Béguin C , title=Standard protecting groups create potent and selective κ opioids: salvinorin B alkoxymethyl ethers , journal=Bioorganic & Medicinal Chemistry , volume=16 , issue=3 , pages=1279–86 , year=2008 , pmid=17981041 , pmc=2568987 , doi=10.1016/j.bmc.2007.10.067 Diterpenes