GW405833.

GW405833 (L-768242) is a synthetic aminoalkylindole, a partial agonist of the CB2 receptor. Gallant et al. (1996) report a Ki of 12.0 nM at human CB2 and 1,917 nM at human CB1; Valenzano et al. (2005) characterised it as a partial agonist (about a 50% reduction in forskolin-stimulated cAMP, compared with CP55940). In rodents, up to 30 mg/kg, it had antihyperalgesic effects in neuropathic, incisional and chronic inflammatory pain models, without analgesia, sedation or catalepsy, which appeared at 100 mg/kg; it penetrates the central nervous system substantially after intraperitoneal injection (Valenzano et al. 2005). The antihyperalgesic effect disappeared in mice lacking CB2, whereas the analgesic and sedative effects at 100 mg/kg persisted (Whiteside et al. 2005), which points to an off-target action at that dose; in rats, the effect on inflammation and hypersensitivity was blocked by SR144528 (Clayton et al. 2002). In a hindpaw incision model, its antiallodynic effect at 10 mg/kg was lower than that of AM1241 (LaBuda et al. 2005). It also antagonises several CB1 signalling pathways (Dhopeshwarkar et al. 2017) and, in the osteoarthritic rat knee, it sensitised joint mechanoreceptors and increased pain through a TRPV1-dependent mechanism (Schuelert and McDougall 2010). All these data are preclinical.

Source

A synthetic molecule of the aminoalkylindole class, absent from cannabis and from any living organism. A research reagent; a fluoroethyl derivative has been labelled with fluorine-18 as a candidate PET imaging tracer for CB2 (Evens et al. 2011).

No biosynthetic pathway: the molecule has no natural equivalent; it is a synthetic indole of the aminoalkylindole class.

European Union

A laboratory reagent; no European Union classification specific to the molecule was found in the sources consulted. Its status depends on the national law of each Member State.

France

Not classified: absent from the ANSM list of narcotics (consolidated version updated 16/02/2026). Its structure (an aroyl group on the indole nitrogen, a morpholinoethyl chain at position 3) does not meet the literal reading of the « Indol-3-yl methanone » entry of Annex IV, which targets a methanone bridge at position 3 of the indole and a substituent on the nitrogen; it falls under no other generic entry. The absence of classification is not a marketing authorisation.

Sources: EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA. Our method.

Family

Synthetic CB receptor agonist › Research ligand or medicine

Class

aminoalkylindole

Verification

Classification, sources and binding values checked on 20 October 2026; text read against its sources and Wikipedia.

Wikipedia (English)

GW-405,833 (new tab)

Article paired by the molecule's structure (InChIKey), revision read on 19 October 2026. Read as a second opinion, never cited as a source.

1. 1Gallant M et al., New class of potent ligands for the human peripheral cannabinoid receptor, Bioorg Med Chem Lett 1996;6(19):2263-2268 (new tab)DOI 10.1016/0960-894X(96)00426-X
2. 2Valenzano KJ et al., Pharmacological and pharmacokinetic characterization of the cannabinoid receptor 2 agonist, GW405833, utilizing rodent models of acute and chronic pain, anxiety, ataxia and catalepsy, Neuropharmacology 2005;48(5):658-672 (new tab)PMID 15814101
3. 3Whiteside GT et al., A role for cannabinoid receptors, but not endogenous opioids, in the antinociceptive activity of the CB2-selective agonist, GW405833, Eur J Pharmacol 2005;528(1-3):65-72 (new tab)PMID 16316650
4. 4Clayton N et al., CB1 and CB2 cannabinoid receptors are implicated in inflammatory pain, Pain 2002;96(3):253-260 (new tab)PMID 11972997
5. 5LaBuda CJ, Koblish M, Little PJ, Cannabinoid CB2 receptor agonist activity in the hindpaw incision model of postoperative pain, Eur J Pharmacol 2005;527(1-3):172-174 (new tab)PMID 16316653
6. 6Dhopeshwarkar A, Murataeva N, Makriyannis A, Straiker A, Mackie K, Two Janus Cannabinoids That Are Both CB2 Agonists and CB1 Antagonists, J Pharmacol Exp Ther 2017;360(2):300-311 (new tab)PMID 27927913
7. 7Schuelert N et al., Paradoxical effects of the cannabinoid CB2 receptor agonist GW405833 on rat osteoarthritic knee joint pain, Osteoarthritis Cartilage 2010;18(11):1536-1543 (new tab)PMID 20863899
8. 8Ermann M et al., Arylsulfonamide CB2 receptor agonists: SAR and optimization of CB2 selectivity, Bioorg Med Chem Lett 2008 (GW405833 as reference compound; EC50 0.65 nM, ChEMBL value) (new tab)PMID 18255291
9. 9Evens N et al., Synthesis, in vitro and in vivo evaluation of fluorine-18 labelled FE-GW405833 as a PET tracer for type 2 cannabinoid receptor imaging, Bioorg Med Chem 2011;19(15):4499-4505 (new tab)PMID 21737287
10. 10ANSM, consolidated list of substances classified as narcotics, updated 16 February 2026, annex IV, heading « Indol-3-yl methanone » (new tab)
11. 11PubChem, GW405833 compound record (CID 9911463) (new tab)

SMILES

CC1=C(C2=C(N1C(=O)C3=C(C(=CC=C3)Cl)Cl)C=CC(=C2)OC)CCN4CCOCC4

Machine-readable entry (JSON)

LLM ingestion format: a structured superset of the entry (identifiers, binding, versioned legal status). Full corpus.