Salvinorin A
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Basic Info
| Common Name | Salvinorin A (F04852) |
| 2D Structure | |
| Description | 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 (L1181). |
| FRCD ID | F04852 |
| CAS Number | 83729-01-5 |
| PubChem CID | 128563 |
| Formula | C23H28O8 |
| IUPAC Name | methyl (2S,4aR,6aR,7R,9S,10aS,10bR)-9-acetyloxy-2-(furan-3-yl)-6a,10b-dimethyl-4,10-dioxo-2,4a,5,6,7,8,9,10a-octahydro-1H-benzo[f]isochromene-7-carboxylate |
| InChI Key | OBSYBRPAKCASQB-AGQYDFLVSA-N |
| InChI | InChI=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/t14-,15-,16-,17-,19-,22-,23-/m0/s1 |
| Canonical SMILES | CC(=O)OC1CC(C2(CCC3C(=O)OC(CC3(C2C1=O)C)C4=COC=C4)C)C(=O)OC |
| Isomeric SMILES | CC(=O)O[C@H]1C[C@H]([C@@]2(CC[C@H]3C(=O)O[C@@H](C[C@@]3([C@H]2C1=O)C)C4=COC=C4)C)C(=O)OC |
| Wikipedia | Salvinorin A |
| Synonyms |
UNII-T56W91NG6J
2H-Naphtho(2,1-c)pyran-7-carboxylic acid, 9-(acetyloxy)-2-(3-furanyl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-, methyl ester, (2S-(2alpha,4aalpha,6abeta,7beta,9beta,10aalpha,10bbeta))-
Salvinorin A
Salvinorin
Divinorin A
83729-01-5
CHEMBL445332
T56W91NG6J
CHEBI:67900
(2S,4aR,6aR,7R,9S,10aS,10bR)-9-(acetyloxy)-2-(3-furanyl)dodechydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho[2,1-c]pyran-7-carboxylic acid methyl ester
|
| Classifies |
Plant Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Lipids and lipid-like molecules |
| Class | Prenol lipids |
| Subclass | Terpene lactones |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Diterpene lactones |
| Alternative Parents | |
| Molecular Framework | Aromatic heteropolycyclic compounds |
| 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 |
| Description | This compound belongs to the class of organic compounds known as diterpene lactones. These are diterpenoids containing a lactone moiety. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 432.469 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 5 |
| Complexity | 792 |
| Monoisotopic Mass | 432.178 |
| Exact Mass | 432.178 |
| XLogP | 2.5 |
| Formal Charge | 0 |
| Heavy Atom Count | 31 |
| Defined Atom Stereocenter Count | 7 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.8821 |
| Human Intestinal Absorption | HIA+ | 0.9921 |
| Caco-2 Permeability | Caco2+ | 0.5432 |
| P-glycoprotein Substrate | Substrate | 0.6394 |
| P-glycoprotein Inhibitor | Inhibitor | 0.9120 |
| Inhibitor | 0.9813 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8219 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.7603 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8364 |
| CYP450 2D6 Substrate | Non-substrate | 0.8073 |
| CYP450 3A4 Substrate | Substrate | 0.6803 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.8486 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9239 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9479 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.8944 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.5539 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.9074 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9660 |
| Non-inhibitor | 0.7515 | |
| AMES Toxicity | Non AMES toxic | 0.9431 |
| Carcinogens | Non-carcinogens | 0.9267 |
| Fish Toxicity | High FHMT | 0.9948 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9955 |
| Honey Bee Toxicity | High HBT | 0.7177 |
| Biodegradation | Not ready biodegradable | 0.9951 |
| Acute Oral Toxicity | I | 0.3955 |
| Carcinogenicity (Three-class) | Non-required | 0.5504 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -4.7392 | LogS |
| Caco-2 Permeability | 0.9866 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 3.5075 | LD50, mol/kg |
| Fish Toxicity | 0.2873 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 1.4089 | pIGC50, ug/L |
Targets
- 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
References
- 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 ]
- 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
References
- 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 ]
- 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
- Mechanism of Action:
- Salvinorin A has been found to be a potent and selective kappa opioid receptor agonist in vitro and in vivo .
References
- 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 ]