Salvinorin A
Encyclopedia
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 psychedelic
/dissociative
effects.
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 a terpenoid
.
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.
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
. Its pharmacological
mechanism was elucidated in the laboratory of Bryan L. Roth.
and x-ray crystallography
to determine the chemical structure of the compound, which was shown to have a bicyclic diterpene
structure. Around the same time, Julian Valdés independently isolated the molecule as part of his PhD research, published in 1983. Valdés named the chemical divinorum, and also isolated an analog that he named divinorum B. The naming was subsequently corrected to salvinorin A and B after the work was published in 1984. Valdés later isolated salvinorin C.
with the chemical formula
C23H28O8. Unlike other known opioid-receptor ligands, salvinorin A is not an alkaloid
—it does not contain a basic
nitrogen
atom
. 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
.
. Synthetic chemicals, such as LSD (active at 20–30 µg doses), can be more potent
. Research has shown that salvinorin A is a potent κ-opioid receptor agonist
. It has a high affinity for the receptor, indicated by the low dissociation constant
of 1.0 nanomolar (nM). It has been reported that the effects of salvinorin A in mice are blocked by κ-opioid receptor antagonist
s. This makes it unlikely that another mechanism contributes independently to the compound's observed effects in mice. However, salvinorin A has recently been found to act as an even more potent D2 receptor partial agonist
, with an affinity of 5–10 nM, an intrinsic activity
of 40–60%, and an EC50
of 50–90 nM, which is several-fold higher than its EC50 of 235 nM for the κ-opioid receptor. This suggests that the D2 receptor may also play an important role in its 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; there are synthetic kappa-opioid agonists, (e.g. enadoline
, ketazocine
, pentazocine
and relatives), which show similar hallucinatory and dissociative effects.
Salvinorin A's potency
should not be confused with toxicity
. Mice chronically
given dosages "many times that of what humans are exposed to" did not show signs of organ damage. However, "further studies should be done on blood pressure effects" and "Pulse pressure did appear to increase with salvinorin A exposure twenty and forty minutes after exposure, however, this increase was not statistically significant" (note that the data shows an increase in pulse pressure that was roughly 1.5–2 times the control group's).
) receptors in inflamed but not normal gut in vivo. 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
. 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.
and acetone
, but not especially so in water.
by 1.5 hours after smoking. Analytical measurements may be performed using gas or liquid chromatography-mass spectrometry
.
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 typical for plant terpenoids.
Similar to many plant-derived psychoactive compounds, salvinorin A is excreted via peltate glandular trichome
s, which reside external to the epidermis
.
cascade to construct the ring system, was achieved in 2007 by Evans and co-workers in 4.5% overall yield over 30 steps.
More recently, a synthesis was published by a Japanese group, requiring 24 steps to yield salvinorin A in 0.15% yield.
An approach to the trans-decalin ring system of salvinorin A has been described by Forsyth (et al.) utilizing an intramolecular Diels-Alder reaction
/Tsuji allylation
strategy.
An attempt at the synthesis of salvinorin A has also been published by a group at RMIT University
, adopting a convergent synthesis
of a functionalized cyclohexanone
with a α,β-unsaturated lactone
.
. The des-acetyl
ated 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 [Ref?]. Salvinorin A seems to be the only active naturally occurring salvinorin.
The newly discovered salvinorin J is most closely related to salvinorin E in structure, with a C-17 secondary alcohol
instead of a ketone
group.
being 10x stronger than salvinorin A. A few derivatives such as herkinorin
have reduced kappa opioid action and instead act as mu opioid
agonists.
and as a therapeutic tool for treating drug addictions. κ-opioid
agonists have very marked effects on all types of addiction including alcohol, cocaine, and opiate abuse.
, due to its psychoactive and analgesic effects.
Salvia divinorum
Salvia divinorum is a psychoactive plant which can induce dissociative effects and is a potent producer of "visions" and other hallucinatory experiences...
, a Mexican plant which has a long history of use as an entheogen
Entheogen
An entheogen , in the strict sense, is a psychoactive substance used in a religious, shamanic, or spiritual context. Historically, entheogens were mostly derived from plant sources and have been used in a variety of traditional religious contexts...
by indigenous Mazatec shamans. Salvinorin A is a hallucinogenic compound
Psychedelics, dissociatives and deliriants
This general group of pharmacological agents can be divided into three broad categories: psychedelics, dissociatives, and deliriants. These classes of psychoactive drugs have in common that they can cause subjective changes in perception, thought, emotion and consciousness...
with psychedelic
Psychedelic drug
A psychedelic substance is a psychoactive drug whose primary action is to alter cognition and perception. Psychedelics are part of a wider class of psychoactive drugs known as hallucinogens, a class that also includes related substances such as dissociatives and deliriants...
/dissociative
Dissociative drug
Dissociatives are a class of psychoactive drugs which are said to reduce or block signals to the conscious mind from other parts of the brain...
effects.
It is structurally distinct from other naturally occurring hallucinogens (such as DMT, psilocybin
Psilocybin
Psilocybin is a naturally occurring psychedelic prodrug, with mind-altering effects similar to those of LSD and mescaline, after it is converted to psilocin. The effects can include altered thinking processes, perceptual distortions, an altered sense of time, and spiritual experiences, as well as...
, and mescaline
Mescaline
Mescaline or 3,4,5-trimethoxyphenethylamine is a naturally occurring psychedelic alkaloid of the phenethylamine class used mainly as an entheogen....
) because it contains no nitrogen
Nitrogen
Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...
atoms, hence it is not an alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
(and cannot be rendered as a salt) but a terpenoid
Terpenoid
The terpenoids , sometimes called isoprenoids, are a large and diverse class of naturally occurring organic chemicals similar to terpenes, derived from five-carbon isoprene units assembled and modified in thousands of ways. Most are multicyclic structures that differ from one another not only in...
.
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.
Salvinorin A is found with several other structurally related salvinorins. Salvinorin is a trans-neoclerodane diterpenoid. It acts as a kappa opioid receptor
Kappa Opioid receptor
The κ-opioid receptor is a protein that in humans is encoded by the OPRK1 gene. The κ-opioid receptor is one of five related receptors that bind opium-like compounds in the brain and are responsible for mediating the effects of these compounds...
agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
and is the first known compound acting on this receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
that is not an alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
. Its pharmacological
Pharmacology
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...
mechanism was elucidated in the laboratory of Bryan L. Roth.
History
Salvinorin A was first described and named in 1982 by Alfredo Ortega and colleagues in Mexico. They used a combination of spectroscopySpectroscopy
Spectroscopy is the study of the interaction between matter and radiated energy. Historically, spectroscopy originated through the study of visible light dispersed according to its wavelength, e.g., by a prism. Later the concept was expanded greatly to comprise any interaction with radiative...
and x-ray crystallography
X-ray crystallography
X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...
to determine the chemical structure of the compound, which was shown to have a bicyclic diterpene
Diterpene
Diterpenes are a type of terpenes composed of four isoprene units. They derive from geranylgeranyl pyrophosphate. Diterpenes form the basis for biologically important compounds such as retinol, retinal, and phytol...
structure. Around the same time, Julian Valdés independently isolated the molecule as part of his PhD research, published in 1983. Valdés named the chemical divinorum, and also isolated an analog that he named divinorum B. The naming was subsequently corrected to salvinorin A and B after the work was published in 1984. Valdés later isolated salvinorin C.
Pharmacology
Salvinorin A is a trans-neoclerodane diterpenoidTerpenoid
The terpenoids , sometimes called isoprenoids, are a large and diverse class of naturally occurring organic chemicals similar to terpenes, derived from five-carbon isoprene units assembled and modified in thousands of ways. Most are multicyclic structures that differ from one another not only in...
with the chemical formula
Chemical formula
A chemical formula or molecular formula is a way of expressing information about the atoms that constitute a particular chemical compound....
C23H28O8. Unlike other known opioid-receptor ligands, salvinorin A is not an alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
—it does not contain a basic
Base (chemistry)
For the term in genetics, see base A base in chemistry is a substance that can accept hydrogen ions or more generally, donate electron pairs. A soluble base is referred to as an alkali if it contains and releases hydroxide ions quantitatively...
nitrogen
Nitrogen
Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...
atom
Atom
The atom is a basic unit of matter that consists of a dense central nucleus surrounded by a cloud of negatively charged electrons. The atomic nucleus contains a mix of positively charged protons and electrically neutral neutrons...
. 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
LSD
Lysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed and open eye visuals, synaesthesia, an...
and mescaline
Mescaline
Mescaline or 3,4,5-trimethoxyphenethylamine is a naturally occurring psychedelic alkaloid of the phenethylamine class used mainly as an entheogen....
.
Potency and selectivity
Salvinorin A "is the most potent naturally occurring hallucinogen." It is active at doses as low as 200 µgMicrogram
In the metric system, a microgram is a unit of mass equal to one millionth of a gram , or 1/1000 of a milligram. It is one of the smallest units of mass commonly used...
. Synthetic chemicals, such as LSD (active at 20–30 µg doses), can be more potent
Potency (pharmacology)
In the field of pharmacology, potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. A highly potent drug evokes a larger response at low concentrations, while a drug of lower potency evokes a small response at low concentrations...
. Research has shown that salvinorin A is a potent κ-opioid receptor agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
. It has a high affinity for the receptor, indicated by the low dissociation constant
Dissociation constant
In chemistry, biochemistry, and pharmacology, a dissociation constant is a specific type of equilibrium constant that measures the propensity of a larger object to separate reversibly into smaller components, as when a complex falls apart into its component molecules, or when a salt splits up into...
of 1.0 nanomolar (nM). It has been reported that the effects of salvinorin A in mice are blocked by κ-opioid receptor antagonist
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
s. This makes it unlikely that another mechanism contributes independently to the compound's observed effects in mice. However, salvinorin A has recently been found to act as an even more potent D2 receptor partial agonist
Partial agonist
Partial agonists bind and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist...
, with an affinity of 5–10 nM, an intrinsic activity
Intrinsic activity
Intrinsic activity or efficacy refers to the relative ability of a drug-receptor complex to produce a maximum functional response. This must be distinguished from the affinity, which is a measure of the ability of the drug to bind to its molecular target, and the EC50, which is a measure of the...
of 40–60%, and an EC50
EC50
The term half maximal effective concentration refers to the concentration of a drug, antibody or toxicant which induces a response halfway between the baseline and maximum after some specified exposure time...
of 50–90 nM, which is several-fold higher than its EC50 of 235 nM for the κ-opioid receptor. This suggests that the D2 receptor may also play an important role in its 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; there are synthetic kappa-opioid agonists, (e.g. enadoline
Enadoline
Enadoline is a drug which acts as a highly selective κ-opioid agonist.In human studies, it produced visual distortions and feelings of dissociation, reminiscent of the effects of Salvinorin A....
, ketazocine
Ketazocine
Ketazocine , also known as ketocyclazocine, is a benzomorphan derivative used in opioid receptor research. Ketocyclazocine is an exogenous opioid that binds to the kappa opioid receptor....
, pentazocine
Pentazocine
Pentazocine is a synthetically prepared prototypical mixed agonist-antagonist narcotic drug of the benzomorphan class of opioids used to treat moderate to moderately severe pain...
and relatives), which show similar hallucinatory and dissociative effects.
Salvinorin A's potency
Potency (pharmacology)
In the field of pharmacology, potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. A highly potent drug evokes a larger response at low concentrations, while a drug of lower potency evokes a small response at low concentrations...
should not be confused with toxicity
Toxicity
Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...
. Mice chronically
Chronic toxicity
Chronic toxicity is a property of a substance that has toxic effects on a living organism, when that organism is exposed to the substance continuously or repeatedly. Compared with acute toxicity.Two distinct situations need to be considered:...
given dosages "many times that of what humans are exposed to" did not show signs of organ damage. However, "further studies should be done on blood pressure effects" and "Pulse pressure did appear to increase with salvinorin A exposure twenty and forty minutes after exposure, however, this increase was not statistically significant" (note that the data shows an increase in pulse pressure that was roughly 1.5–2 times the control group's).
Effect on intestinal motility
Salvinorin A is capable of inhibiting excess intestinal motility (e.g. diarrhea), through a combination of k-opioid and cannabinoid (mainly CB1 receptorCannabinoid receptor type 1
The cannabinoid receptor type 1, often abbreviated to CB1, is a G protein-coupled cannabinoid receptor located in the brain. It is activated by endocannabinoid neurotransmitters including anandamide and by the compound THC, found in the psychoactive drug cannabis.-Expression:The CB1 receptor is...
) receptors in inflamed but not normal gut in vivo. The mechanism of action for salvinorin A on ileal
Ileum
The ileum is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine may be used instead of ileum.The ileum follows the duodenum...
tissue has been described as 'prejunctional', as it was able to modify electrically induced contractions, but not those of exogenous
Exogenous
Exogenous refers to an action or object coming from outside a system. It is the opposite of endogenous, something generated from within the system....
acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
. 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.
Solubility
Salvinorin A is soluble in organic solvents such as ethanolEthanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
and acetone
Acetone
Acetone is the organic compound with the formula 2CO, a colorless, mobile, flammable liquid, the simplest example of the ketones.Acetone is miscible with water and serves as an important solvent in its own right, typically as the solvent of choice for cleaning purposes in the laboratory...
, but not especially so in water.
Detection in urine
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, but the levels fell below the detection limitDetection limit
In analytical chemistry, the detection limit, lower limit of detection, or LOD , is the lowest quantity of a substance that can be distinguished from the absence of that substance within a stated confidence limit...
by 1.5 hours after smoking. Analytical measurements may be performed using gas or liquid chromatography-mass spectrometry
Liquid chromatography-mass spectrometry
Liquid chromatography–mass spectrometry is an analytical chemistry technique that combines the physical separation capabilities of liquid chromatography with the mass analysis capabilities of mass spectrometry. LC-MS is a powerful technique used for many applications which has very high...
.
Associated compounds
Many other terpenoids have been isolated from Salvia divinorum, including other salvinorins and related compounds 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.Synthesis
Biosynthesis
The biogenic origin of salvinorin A synthesis has been elucidated using nuclear magnetic resonanceNuclear magnetic resonance
Nuclear magnetic resonance is a physical phenomenon in which magnetic nuclei in a magnetic field absorb and re-emit electromagnetic radiation...
and ESI
Electrospray ionization
Electrospray ionization is a technique used in mass spectrometry to produce ions. It is especially useful in producing ions from macromolecules because it overcomes the propensity of these molecules to fragment when ionized...
-MS
Mass spectrometry
Mass spectrometry is an analytical technique that measures the mass-to-charge ratio of charged particles.It is used for determining masses of particles, for determining the elemental composition of a sample or molecule, and for elucidating the chemical structures of molecules, such as peptides and...
analysis of incorporated precursors labeled
Isotopic labeling
Isotopic labeling is a technique for tracking the passage of a sample of substance through a system. The substance is 'labeled' by including unusual isotopes in its chemical composition...
with stable isotopes of carbon
Carbon
Carbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...
(Carbon-13
Carbon-13
Carbon-13 is a natural, stable isotope of carbon and one of the environmental isotopes. It makes up about 1.1% of all natural carbon on Earth.- Detection by mass spectrometry :...
13C) and hydrogen
Hydrogen
Hydrogen is the chemical element with atomic number 1. It is represented by the symbol H. With an average atomic weight of , hydrogen is the lightest and most abundant chemical element, constituting roughly 75% of the Universe's chemical elemental mass. Stars in the main sequence are mainly...
(Deuterium
Deuterium
Deuterium, also called heavy hydrogen, is one of two stable isotopes of hydrogen. It has a natural abundance in Earth's oceans of about one atom in of hydrogen . Deuterium accounts for approximately 0.0156% of all naturally occurring hydrogen in Earth's oceans, while the most common isotope ...
2H). It "is biosynthesized via the 1-deoxy-d-xylulose-5-phosphate pathway
Non-mevalonate pathway
The non-mevalonate pathway or 2-C-methyl-D-erythritol 4-phosphate/1-deoxy-D-xylulose 5-phosphate pathway of isoprenoid biosynthesis is an alternative metabolic pathway leading to the formation of isopentenyl pyrophosphate and dimethylallyl pyrophosphate that has been elucidated only...
," rather than the classic mevalonate pathway typical for plant terpenoids.
Similar to many plant-derived psychoactive compounds, salvinorin A is excreted via peltate glandular trichome
Trichome
Trichomes are fine outgrowths or appendages on plants and certain protists. These are of diverse structure and function. Examples are hairs, glandular hairs, scales, and papillae.- Algal trichomes :...
s, which reside external to the epidermis
Epidermis (botany)
The epidermis is a single-layered group of cells that covers plants' leaves, flowers, roots and stems. It forms a boundary between the plant and the external environment. The epidermis serves several functions, it protects against water loss, regulates gas exchange, secretes metabolic compounds,...
.
Chemical synthesis
A total asymmetric synthesis of salvinorin A, which relies on a transannular Michael reactionMichael reaction
The Michael reaction or Michael addition is the nucleophilic addition of a carbanion or another nucleophile to an alpha, beta unsaturated carbonyl compound. It belongs to the larger class of conjugate additions. This is one of the most useful methods for the mild formation of C-C bonds...
cascade to construct the ring system, was achieved in 2007 by Evans and co-workers in 4.5% overall yield over 30 steps.
More recently, a synthesis was published by a Japanese group, requiring 24 steps to yield salvinorin A in 0.15% yield.
An approach to the trans-decalin ring system of salvinorin A has been described by Forsyth (et al.) utilizing an intramolecular Diels-Alder reaction
Diels-Alder reaction
The Diels–Alder reaction is an organic chemical reaction between a conjugated diene and a substituted alkene, commonly termed the dienophile, to form a substituted cyclohexene system. The reaction can proceed even if some of the atoms in the newly formed ring are not carbon...
/Tsuji allylation
Intramolecular Diels-Alder Cycloaddition
In organic chemistry, an intramolecular Diels-Alder cycloaddition is a Diels–Alder reaction in which the diene and a dienophile are both part of the same molecule...
strategy.
An attempt at the synthesis of salvinorin A has also been published by a group at RMIT University
RMIT University
RMIT University is an Australian public university located in Melbourne, Victoria. It has two branches, referred to as RMIT University in Australia and RMIT International University in Vietnam....
, adopting a convergent synthesis
Convergent synthesis
In chemistry a convergent synthesis is a strategy that aims to improve the efficiency of multi-step chemical synthesis, most often in organic synthesis...
of a functionalized cyclohexanone
Cyclohexanone
Cyclohexanone is the organic compound with the formula 5CO. The molecule consists of six-carbon cyclic molecule with a ketone functional group. This colorless oil has an odor reminiscent of peardrop sweets as well as acetone. Over time, samples assume a yellow color due to oxidation...
with a α,β-unsaturated lactone
Lactone
In chemistry, a lactone is a cyclic ester which can be seen as the condensation product of an alcohol group -OH and a carboxylic acid group -COOH in the same molecule...
.
Other salvinorins
Salvinorin A is one of several structurally related salvinorins found in the Salvia divinorum plant. Salvinorin A can be synthesized from the inactive salvinorin B by acetylationAcetylation
Acetylation describes a reaction that introduces an acetyl functional group into a chemical compound...
. The des-acetyl
Acetyl
In organic chemistry, acetyl is a functional group, the acyl with chemical formula COCH3. It is sometimes represented by the symbol Ac . The acetyl group contains a methyl group single-bonded to a carbonyl...
ated 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
Ligand binding assay
In medicine and pharmacology, a ligand binding assay is a technique to identify the presence of a molecule and quantify it. There are numerous types of ligand binding assays, both radioactive and non-radioactive. As such, ligand binding assays are superset of radiobinding assays, which are the...
could not confirm this [Ref?]. Salvinorin A seems to be the only active naturally occurring salvinorin.
| Name | Structure | R1 | R2 | Activity |
|---|---|---|---|---|
| Salvinorin A |  |
-OCOCH3 | − | active |
| Salvinorin B | -OH | − | inactive | |
| Salvinorin C |  |
-OCOCH3 | -OCOCH3 | unknown |
| Salvinorin D | -OH | -OCOCH3 | inactive | |
| Salvinorin E | -OCOCH3 | -OH | inactive | |
| Salvinorin F | -H | -OH | unknown |
The newly discovered salvinorin J is most closely related to salvinorin E in structure, with a C-17 secondary alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
instead of a ketone
Ketone
In organic chemistry, a ketone is an organic compound with the structure RCR', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology...
group.
Semi-synthetic analogues
Research on salvinorin derivatives has produced a number of semi-synthetic compounds, several of which can be conveniently made from salvinorin B. Most derivatives are selective kappa opioid agonists as with salvinorin A, although some are even more potent, with the most potent compound 2-ethoxymethyl salvinorin B2-Ethoxymethyl Salvinorin B
2-Ethoxymethyl salvinorin B is a semi-synthetic analogue of the natural product salvinorin A, with a longer duration of action of around 3 hours , and increased affinity and intrinsic activity at the κ-opioid receptor...
being 10x stronger than salvinorin A. A few derivatives such as herkinorin
Herkinorin
Herkinorin is an opioid analgesic that is an 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 of which Salvinorin A is a member.Unlike Salvinorin A which is a...
have reduced kappa opioid action and instead act as mu opioid
Mu Opioid receptor
The μ-opioid receptors are a class of opioid receptors with high affinity for enkephalins and beta-endorphin but low affinity for dynorphins. They are also referred to as μ opioid peptide receptors. The prototypical μ receptor agonist is the opium alkaloid morphine; μ refers to morphine...
agonists.
- 2-Methoxymethyl Salvinorin B2-Methoxymethyl Salvinorin B2-Methoxymethyl salvinorin B is a semi-synthetic analogue of the natural product salvinorin A which is used in scientific research. It has a longer duration of action of around 2–3 hours, compared to less than 30 minutes for salvinorin A, and has increased affinity and efficacy at the κ-opioid...
Pharmaceutical action
Results from a small study by an assistant professor at the University of Iowa indicate that it may have potential as an analgesicAnalgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
and as a therapeutic tool for treating drug addictions. κ-opioid
Kappa Opioid receptor
The κ-opioid receptor is a protein that in humans is encoded by the OPRK1 gene. The κ-opioid receptor is one of five related receptors that bind opium-like compounds in the brain and are responsible for mediating the effects of these compounds...
agonists have very marked effects on all types of addiction including alcohol, cocaine, and opiate abuse.
Legality
Salvinorin A is sometimes regulated together with its host, Salvia divinorumSalvia divinorum
Salvia divinorum is a psychoactive plant which can induce dissociative effects and is a potent producer of "visions" and other hallucinatory experiences...
, due to its psychoactive and analgesic effects.
External links
- The Salvia divinorum Research and Information Center (Daniel Siebert)
- Erowid Salvia divinorum vault
- Lycaeum Salvinorin A
- Tryptamind Salvinorin A Downloadable salvinorin extraction photos.