WIN 55,212-2
[(11R)-2-methyl-11-(morpholin-4-ylmethyl)-9-oxa-1-azatricyclo[6.3.1.04,12]dodeca-2,4(12),5,7-tetraen-3-yl]-naphthalen-1-ylmethanone
Overview
WIN 55,212-2 belongs to Cannabinoids.
Effects
- In animal models: the full 'cannabinoid tetrad', analgesia, lowered body temperature, catalepsy and reduced movement, more potent than THC.
- Predicted human effects (from the related full-agonist 'Spice/K2' synthetic cannabinoids): intense intoxication, anxiety or panic, rapid heartbeat and possible psychosis.
- No characterised or safe human dose.
Dosing & duration
Used as a laboratory reagent (dissolved for in-vitro and animal studies). There is no established or safe human dose. Figures for human use do not exist.. WIN 55,212-2 is a research chemical with no validated human use. There is no known safe dose or route, as a high-efficacy CB1 full agonist it would be expected to carry the acute risks of the 'Spice/K2' synthetic cannabinoids (severe intoxication, psychosis, seizures, cardiac events).
Dose ranges
Duration
Chemical & Physical Properties
| Formula | C27H26N2O3 |
| Molar mass | 426.5 g/mol |
| State | Solid (usually the mesylate salt, white to off-white crystalline powder) |
| Melting point | unavailable: true. reason: no reliable experimental melting point is reported for this research chemical (free base or mesylate salt) |
| Boiling point | Not reported |
| Density | Not reported |
| Vapor pressure | Not reported |
| pKa | Not reported |
| LogP | 4.4 (predicted, XLogP3, free base) |
| Solubility | Mesylate salt: soluble in DMSO and ethanol. Sparingly soluble in water (research-reagent solvents) |
| Refractive index | Not reported |
Identifiers & Synonyms
| CAS | 131543-22-1 |
| CAS (enantiomer) | |
| PubChem CID | 5311501 |
| InChIKey | HQVHOQAKMCMIIM-HXUWFJFHSA-N |
| InChI | InChI=1S/C27H26N2O3/c1-18-25(27(30)22-9-4-7-19-6-2-3-8-21(19)22)23-10-5-11-24-26(23)29(18)20(17-32-24)16-28-12-14-31-15-13-28/h2-11,20H,12-17H2,1H3/t20-/m1/s1 |
| SMILES | CC1=C(C2=C3N1[C@@H](COC3=CC=C2)CN4CCOCC4)C(=O)C5=CC=CC6=CC=CC=C65 |
Synonyms
Pharmacodynamics & Biochemistry
WIN 55,212-2 is a synthetic cannabinoid of the aminoalkylindole class: structurally unrelated to THC, yet a potent full agonist at both cannabinoid receptors. It activates CB1 (Kᵢ ≈16 nM) and CB2 (Kᵢ ≈1 nM) with higher affinity than THC and, unlike THC's partial agonism, produces the full receptor response, so in animals it reproduces and exceeds the classic cannabinoid effects (analgesia, hypothermia, catalepsy, reduced movement). It also has documented secondary actions, including subunit-specific modulation of glycine receptors and agonism at the PPARα/γ nuclear receptors. Its activity is strongly stereospecific: the name 'WIN 55,212-2' refers specifically to the active (R)-(+) enantiomer, while the mirror-image (S)-(−) enantiomer, 'WIN 55,212-3', is essentially inactive at cannabinoid receptors. That clean enantiomer split made it a key pharmacological tool for showing that cannabinoid effects are receptor-mediated. WIN 55,212-2 is one of the most widely used cannabinoid research compounds, employed to probe CB1/CB2 signalling, analgesia and neuroprotection. Its aminoalkylindole/naphthoylindole chemistry also historically inspired the naphthoylindole 'Spice/K2' synthetic cannabinoids that later appeared as drugs of misuse, though WIN 55,212-2 itself is a laboratory reagent rather than a street product.
Biological targets
- CB1
- CB2
Binding & functional measurements
| Target | Measurement | Species |
|---|---|---|
| CB1 receptor | EC50 284 nM | Human |
| CB2 receptor | EC50 62 nM | Human |
Pharmacokinetics
| Bioavailability | Not reported |
| Tmax | Not reported |
| Half-life | Not established in humans (research compound) |
| Vd | Not reported |
| Protein binding | Not reported |
| Metabolism | Hepatic (animal studies) |
| Excretion | Not reported |
Toxicology & Safety
Not reported
WIN 55,212-2 is a research chemical, not a medicine or a quality-controlled consumer product, and there is essentially no human safety data. As a high-affinity FULL agonist at CB1 (more efficacious than THC), it would be expected to produce intense and potentially dangerous cannabinoid effects: severe intoxication, anxiety and panic, tachycardia and other cardiovascular effects, sedation, and psychotomimetic reactions: of the kind seen with the related 'Spice/K2' full-agonist synthetic cannabinoids, which have caused seizures, acute psychosis and deaths. Because it is sold only as a laboratory reagent, its dose, purity and effects in humans are uncharacterised, and there is no safe recreational use. It should be handled as a potent bioactive research chemical.[2]
Legal Status
US: Schedule I. UK: Class B. DE: NpSG
Interactions & Contraindications
Drug interactions
Contraindications
No interactions or contraindications listed.
Usage & Context
- A laboratory research tool: one of the most widely used synthetic cannabinoids for studying CB1/CB2 receptor pharmacology, signalling, analgesia and neuroprotection.
- Its aminoalkylindole/naphthoylindole chemistry influenced the later 'Spice/K2' synthetic cannabinoids that became drugs of misuse, though WIN 55,212-2 itself is a reagent, not a consumer product.
- No approved medical use.
Sources & Evidence
- PubChem: (R)-(+)-WIN 55,212-2 (CID 5311501) — identifiers & computed properties
- Wikipedia: WIN 55,212-2 — aminoalkylindole synthetic cannabinoid, CB1/CB2 full agonist, (R)/(S) stereospecificity, research use & legal status CC BY-SA 4.0
- Felder CC, Joyce KE, Briley EM, et al. (1995). Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors. Mol Pharmacol 48:443-50.
PMID 7565624
- Shire D, Calandra B, Rinaldi-Carmona M, et al. (1996). Molecular cloning, expression and function of the murine CB2 peripheral cannabinoid receptor. Biochim Biophys Acta 1307:132-6.
PMID 8679694 · doi:10.1016/0167-4781(96)00047-4
- Showalter VM, Compton DR, Martin BR, et al. (1996). Evaluation of binding in a transfected cell line expressing a peripheral cannabinoid receptor (CB2): identification of cannabinoid receptor subtype selective ligands. J Pharmacol Exp Ther 278:989-99.
PMID 8819477
- Yang Z, Aubrey KR, Alroy I, et al. (2008). Subunit-specific modulation of glycine receptors by cannabinoids and N-arachidonyl-glycine. Biochem Pharmacol 76:1014-23.
PMID 18755158 · doi:10.1016/j.bcp.2008.07.037
- DEA Diversion Control Division: Controlled Substance Schedules — naphthoylindole synthetic cannabinoids (incl. WIN 55,212-2) are Schedule I
- IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb) CC BY-SA 4.0