You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Toxin, Toxin Target Database.
Record Information
Version2.0
Creation Date2009-07-30 17:59:08 UTC
Update Date2014-12-24 20:26:07 UTC
Accession NumberT3D3532
Identification
Common NameSalvinorin A
ClassSmall Molecule
DescriptionSalvinorin 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 (10).
Compound Type
  • Ester
  • Ether
  • Natural Compound
  • Organic Compound
  • Plant Toxin
Chemical Structure
Thumb
Synonyms
Synonym
Diviner's sage
Divinorin a
Herbal ecstasy
Mexican mint
Salvinorin
Salvinorin a
Ska maria pastora
Chemical FormulaC23H28O8
Average Molecular Mass432.464 g/mol
Monoisotopic Mass432.178 g/mol
CAS Registry Number83729-01-5
IUPAC Namemethyl 9-(acetyloxy)-2-(furan-3-yl)-6a,10b-dimethyl-4,10-dioxo-dodecahydro-1H-naphtho[2,1-c]pyran-7-carboxylate
Traditional Namemethyl 9-(acetyloxy)-2-(furan-3-yl)-6a,10b-dimethyl-4,10-dioxo-octahydro-1H-naphtho[2,1-c]pyran-7-carboxylate
SMILESCOC(=O)C1CC(OC(C)=O)C(=O)C2C1(C)CCC1C(=O)OC(CC21C)C1=COC=C1
InChI IdentifierInChI=1S/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
InChI KeyInChIKey=OBSYBRPAKCASQB-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as diterpene lactones. These are diterpenoids containing a lactone moiety.
KingdomChemical entities
Super ClassOrganic compounds
ClassLipids and lipid-like molecules
Sub ClassPrenol lipids
Direct ParentDiterpene lactones
Alternative Parents
Substituents
  • Diterpene lactone
  • Diterpenoid
  • Clerodane diterpenoid
  • Naphthopyran
  • Naphthalene
  • Tricarboxylic acid or derivatives
  • Delta valerolactone
  • Delta_valerolactone
  • Alpha-acyloxy ketone
  • Pyran
  • Oxane
  • Methyl ester
  • Furan
  • Heteroaromatic compound
  • Carboxylic acid ester
  • Ketone
  • Lactone
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Oxacycle
  • Organooxygen compound
  • Organic oxide
  • Organic oxygen compound
  • Carbonyl group
  • Hydrocarbon derivative
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceColorless crystals from methanol (2).
Experimental Properties
PropertyValue
Melting Point238-244°C
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.08 mg/mLALOGPS
logP2.48ALOGPS
logP2.39ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)16.45ChemAxon
pKa (Strongest Basic)-3.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area109.11 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity106 m3·mol-1ChemAxon
Polarizability44.23 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-1008900000-3dde4855bc69f27483e4View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0gi3-1019500000-0d06ceb5fd22972dfc1eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0gxw-3249100000-797004a599225d2018a4View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001r-3009600000-a9c68bc515eddd483f7dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a5i-3009200000-0bf80f4121126284c9d4View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9006000000-f6147bd53d5e352b972cView in MoNA
Toxicity Profile
Route of ExposureIngestion (11) ; dermal (11)
Mechanism of ToxicitySalvinorin A, the active component of the hallucinogenic sage Salvia divinorum, is an apparently selective and highly potent kappa-opioid receptor (KOR) agonist. Salvinorin A is unique among ligands for peptidergic G protein-coupled receptors in being nonnitrogenous and lipid-like in character (3).
MetabolismSalvinorin A’s chemical structure suggests that it may be a substrate of CYP450 (oxidative metabolism), UGT (hydrolysis) or carboxylesterases (ChEs) (hydrolysis). In addition, as observed for CYP1A1, CPY2C18 and CYP2E1, Salvinorin A metabolism via UGTB27 appears to be saturable at higher concentrations.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity (not listed by IARC). (12)
Uses/SourcesTraditional medicine used by the Mazatec people of Oaxaca, Mexico (2).
Minimum Risk LevelNot Available
Health EffectsPsychedelic-like changes in visual perception, mood, and body sensations (4).
SymptomsHallucinations or delusional episodes that mimic psychosis. ; emotional swings; feelings of detachment; and importantly, a highly modified perception of external reality and the self, which leads to a decreased ability to interact with one's surroundings (4).
TreatmentTreatment for salvinorin A overdose would be similar to the treatments for hallucinogen intoxication. (5)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID128563
ChEMBL IDNot Available
ChemSpider IDNot Available
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDSalvinorin A
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkSalvinorin
References
Synthesis ReferenceNot Available
MSDST3D3532.pdf
General References
  1. Teksin ZS, Lee IJ, Nemieboka NN, Othman AA, Upreti VV, Hassan HE, Syed SS, Prisinzano TE, Eddington ND: Evaluation of the transport, in vitro metabolism and pharmacokinetics of Salvinorin A, a potent hallucinogen. Eur J Pharm Biopharm. 2009 Jun;72(2):471-7. doi: 10.1016/j.ejpb.2009.01.002. [19462483 ]
  2. McAlister ED, Van Vugt DA: Effect of leptin administration versus re-feeding on hypothalamic neuropeptide gene expression in fasted male rats. Can J Physiol Pharmacol. 2004 Dec;82(12):1128-34. [15644956 ]
  3. Muhlhausler BS, Adam CL, Marrocco EM, Findlay PA, Roberts CT, McFarlane JR, Kauter KG, McMillen IC: Impact of glucose infusion on the structural and functional characteristics of adipose tissue and on hypothalamic gene expression for appetite regulatory neuropeptides in the sheep fetus during late gestation. J Physiol. 2005 May 15;565(Pt 1):185-95. Epub 2005 Jan 20. [15661821 ]
  4. Loos RJ, Rankinen T, Tremblay A, Perusse L, Chagnon Y, Bouchard C: Melanocortin-4 receptor gene and physical activity in the Quebec Family Study. Int J Obes (Lond). 2005 Apr;29(4):420-8. [15597110 ]
  5. Scruggs P, Lai CC, Scruggs JE, Dun NJ: Cocaine- and amphetamine-regulated transcript peptide potentiates spinal glutamatergic sympathoexcitation in anesthetized rats. Regul Pept. 2005 Apr 15;127(1-3):79-85. [15680473 ]
  6. National Institute on Drug Abuse (NIDA) (2007). Infofacts: Salvia.
  7. O'Neil MJ (ed) (2006). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th ed. Whitehouse Station, NJ: Merck and Co., Inc.
  8. Vortherms TA et al; J Biol Chem 282 (5): 3146-56 (2007).
  9. Biller J (2007). The Interface of Neurology & Internal Medicine. Philadelphia, PA: Wolters Kluwer Health, Lippincott/Williams and Wilkins.
  10. Wikipedia. Salvinorin. Last Updated 8 August 2009. [Link]
  11. Wikipedia. Phytotoxin. Last Updated 7 August 2009. [Link]
  12. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Opioid receptor activity
Specific Function:
G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain. Plays a role in mediating reduced physical activity upon treatment with synthetic opioids. Plays a role in the regulation of salivation in response to synthetic opioids. May play a role in arousal and regulation of autonomic and neuroendocrine functions.
Gene Name:
OPRK1
Uniprot ID:
P41145
Molecular Weight:
42644.665 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.00075 uMNot AvailableBindingDB 50159165
Inhibitory0.0008 uMNot AvailableBindingDB 50159165
Inhibitory0.0013 uMNot AvailableBindingDB 50159165
Inhibitory0.0019 uMNot AvailableBindingDB 50159165
Inhibitory0.0024 uMNot AvailableBindingDB 50159165
Inhibitory0.0025 uMNot AvailableBindingDB 50159165
Inhibitory0.0026 uMNot AvailableBindingDB 50159165
Inhibitory0.003 uMNot AvailableBindingDB 50159165
Inhibitory0.0057 uMNot AvailableBindingDB 50159165
Inhibitory0.0074 uMNot AvailableBindingDB 50159165
References
  1. Tidgewell K, Groer CE, Harding WW, Lozama A, Schmidt M, Marquam A, Hiemstra J, Partilla JS, Dersch CM, Rothman RB, Bohn LM, Prisinzano TE: Herkinorin analogues with differential beta-arrestin-2 interactions. J Med Chem. 2008 Apr 24;51(8):2421-31. doi: 10.1021/jm701162g. Epub 2008 Apr 2. [18380425 ]
  2. Fichna J, Lewellyn K, Yan F, Roth BL, Zjawiony JK: Synthesis and biological evaluation of new salvinorin A analogues incorporating natural amino acids. Bioorg Med Chem Lett. 2011 Jan 1;21(1):160-3. doi: 10.1016/j.bmcl.2010.11.046. Epub 2010 Nov 11. [21115248 ]
  3. Ghirmai S, Azar MR, Cashman JR: Synthesis and pharmacological evaluation of 6-naltrexamine analogs for alcohol cessation. Bioorg Med Chem. 2009 Sep 15;17(18):6671-81. doi: 10.1016/j.bmc.2009.07.069. Epub 2009 Aug 6. [19683449 ]
  4. Beguin C, Richards MR, Li JG, Wang Y, Xu W, Liu-Chen LY, Carlezon WA Jr, Cohen BM: Synthesis and in vitro evaluation of salvinorin A analogues: effect of configuration at C(2) and substitution at C(18). Bioorg Med Chem Lett. 2006 Sep 1;16(17):4679-85. Epub 2006 Jun 13. [16777411 ]
  5. Lee DY, He M, Liu-Chen LY, Wang Y, Li JG, Xu W, Ma Z, Carlezon WA Jr, Cohen B: Synthesis and in vitro pharmacological studies of new C(4)-modified salvinorin A analogues. Bioorg Med Chem Lett. 2006 Nov 1;16(21):5498-502. Epub 2006 Aug 30. [16945525 ]
  6. Harding WW, Tidgewell K, Byrd N, Cobb H, Dersch CM, Butelman ER, Rothman RB, Prisinzano TE: Neoclerodane diterpenes as a novel scaffold for mu opioid receptor ligands. J Med Chem. 2005 Jul 28;48(15):4765-71. [16033256 ]
  7. Tidgewell K, Harding WW, Lozama A, Cobb H, Shah K, Kannan P, Dersch CM, Parrish D, Deschamps JR, Rothman RB, Prisinzano TE: Synthesis of salvinorin A analogues as opioid receptor probes. J Nat Prod. 2006 Jun;69(6):914-8. [16792410 ]
  8. Yamaotsu N, Fujii H, Nagase H, Hirono S: Identification of the three-dimensional pharmacophore of kappa-opioid receptor agonists. Bioorg Med Chem. 2010 Jun 15;18(12):4446-52. doi: 10.1016/j.bmc.2010.04.069. Epub 2010 Apr 28. [20478711 ]
  9. Munro TA, Duncan KK, Xu W, Wang Y, Liu-Chen LY, Carlezon WA Jr, Cohen BM, Beguin C: Standard protecting groups create potent and selective kappa opioids: salvinorin B alkoxymethyl ethers. Bioorg Med Chem. 2008 Feb 1;16(3):1279-86. Epub 2007 Oct 24. [17981041 ]
  10. Beguin C, Duncan KK, Munro TA, Ho DM, Xu W, Liu-Chen LY, Carlezon WA Jr, Cohen BM: Modification of the furan ring of salvinorin A: identification of a selective partial agonist at the kappa opioid receptor. Bioorg Med Chem. 2009 Feb 1;17(3):1370-80. doi: 10.1016/j.bmc.2008.12.012. Epub 2008 Dec 14. [19147366 ]
  11. Beguin C, Potuzak J, Xu W, Liu-Chen LY, Streicher JM, Groer CE, Bohn LM, Carlezon WA Jr, Cohen BM: Differential signaling properties at the kappa opioid receptor of 12-epi-salvinorin A and its analogues. Bioorg Med Chem Lett. 2012 Jan 15;22(2):1023-6. doi: 10.1016/j.bmcl.2011.11.128. Epub 2011 Dec 7. [22204910 ]
  12. Lozama A, Cunningham CW, Caspers MJ, Douglas JT, Dersch CM, Rothman RB, Prisinzano TE: Opioid receptor probes derived from cycloaddition of the hallucinogen natural product salvinorin A. J Nat Prod. 2011 Apr 25;74(4):718-26. doi: 10.1021/np1007872. Epub 2011 Feb 21. [21338114 ]
  13. Lovell KM, Vasiljevik T, Araya JJ, Lozama A, Prevatt-Smith KM, Day VW, Dersch CM, Rothman RB, Butelman ER, Kreek MJ, Prisinzano TE: Semisynthetic neoclerodanes as kappa opioid receptor probes. Bioorg Med Chem. 2012 May 1;20(9):3100-10. doi: 10.1016/j.bmc.2012.02.040. Epub 2012 Mar 1. [22464684 ]
General Function:
Voltage-gated calcium channel activity
Specific Function:
Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors. The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extend to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15. They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B. Also couples to adenylate cyclase stimulatory G alpha proteins. The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4. Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization. Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction. The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins. The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation. Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling. Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling. Endogenous ligands induce rapid desensitization, endocytosis and recycling whereas morphine induces only low desensitization and endocytosis. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis. Isoform 12 couples to GNAS and is proposed to be involved in excitatory effects. Isoform 16 and isoform 17 do not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity.
Gene Name:
OPRM1
Uniprot ID:
P35372
Molecular Weight:
44778.855 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory1.37 uMNot AvailableBindingDB 50159165
Inhibitory4.37 uMNot AvailableBindingDB 50159165
Inhibitory>1 uMNot AvailableBindingDB 50159165
Inhibitory>10 uMNot AvailableBindingDB 50159165
References
  1. Lovell KM, Vasiljevik T, Araya JJ, Lozama A, Prevatt-Smith KM, Day VW, Dersch CM, Rothman RB, Butelman ER, Kreek MJ, Prisinzano TE: Semisynthetic neoclerodanes as kappa opioid receptor probes. Bioorg Med Chem. 2012 May 1;20(9):3100-10. doi: 10.1016/j.bmc.2012.02.040. Epub 2012 Mar 1. [22464684 ]
  2. Tidgewell K, Groer CE, Harding WW, Lozama A, Schmidt M, Marquam A, Hiemstra J, Partilla JS, Dersch CM, Rothman RB, Bohn LM, Prisinzano TE: Herkinorin analogues with differential beta-arrestin-2 interactions. J Med Chem. 2008 Apr 24;51(8):2421-31. doi: 10.1021/jm701162g. Epub 2008 Apr 2. [18380425 ]
  3. Harding WW, Tidgewell K, Byrd N, Cobb H, Dersch CM, Butelman ER, Rothman RB, Prisinzano TE: Neoclerodane diterpenes as a novel scaffold for mu opioid receptor ligands. J Med Chem. 2005 Jul 28;48(15):4765-71. [16033256 ]
  4. Tidgewell K, Harding WW, Lozama A, Cobb H, Shah K, Kannan P, Dersch CM, Parrish D, Deschamps JR, Rothman RB, Prisinzano TE: Synthesis of salvinorin A analogues as opioid receptor probes. J Nat Prod. 2006 Jun;69(6):914-8. [16792410 ]
  5. Fichna J, Lewellyn K, Yan F, Roth BL, Zjawiony JK: Synthesis and biological evaluation of new salvinorin A analogues incorporating natural amino acids. Bioorg Med Chem Lett. 2011 Jan 1;21(1):160-3. doi: 10.1016/j.bmcl.2010.11.046. Epub 2010 Nov 11. [21115248 ]
General Function:
Opioid receptor activity
Specific Function:
G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine.
Gene Name:
OPRD1
Uniprot ID:
P41143
Molecular Weight:
40368.235 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>10 uMNot AvailableBindingDB 50159165
References
  1. Roth BL, Baner K, Westkaemper R, Siebert D, Rice KC, Steinberg S, Ernsberger P, Rothman RB: Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11934-9. Epub 2002 Aug 21. [12192085 ]