It is a potent and selective CB2 receptor partial agonist (EC50 = 0.65 nM; maximum inhibition = 44.6%). Binds with high affinity to both human and rat CB2 receptors and displays ~ 1200-fold selectivity over CB1 (Ki values are 3.92 and 4772 nM for human recombinant CB2 and CB1 receptors respectively). Produces potent antihyperalgesic effects in several rodent models of pain.
ChEBI: (2,3-dichlorophenyl)-[5-methoxy-2-methyl-3-[2-(4-morpholinyl)ethyl]-1-indolyl]methanone is a N-acylindole.
Potent and selective CB 2 receptor partial agonist (EC 50 = 0.65 nM; maximum inhibition = 44.6%). Binds with high affinity to both human and rat CB 2 receptors and displays ~ 1200-fold selectivity over CB 1 (K i values are 3.92 and 4772 nM for human recombinant CB 2 and CB 1 receptors respectively). Produces potent antihyperalgesic effects in several rodent models of pain.
GW405833 is a selective cannabanoid CB2 receptor agonist; analgesic. GW405833 binds with high affinity at both human and rat CB2 receptors (Ki′s 3.9 and 3.6 nM); acts as a partial agonist (50% inhibition of forskolin-stimulated cAMP formation compared to full agonist CP55,940). GW405833 has potent analgesic activity in rat models of inflammatory, neuropathic and incisional pain; devoid of CNS effects common with CB1 agonists.
GW-405833 (3, 10 and 30 mg/kg; i.p.) reverses hyperalgesia in both pain models in a dose-dependent manner in WT mice, while this effect is preserves in CB1KO mice but absent in CB2KO mice[1].
GW-405833 (30 mg/kg; i.p.) does not induce cataplexy, motor ataxia, hypothermia, or acute tail-flick antiesthesia in CD1KO mice[1].
| Animal Model: | CB1KO mice, CB2KO mice, WT mice[1] |
| Dosage: | 3, 10 and 30 mg/kg |
| Administration: | Intraperitoneal injection (i.p.) |
| Result: | Increased the paw withdrawal threshold in CB2KO and WT mice in a dose-dependent manner.
Restored mechanical paw withdrawal thresholds relative to baseline in CB2KO and WT mice at doses as low as 10 mg/kg.
Retained antiallodynic effects in CB2KO mice.
Produced a dose-dependent increase in mechanical threshold in WT mice, but this antiallodynic effect was absent in CB1KO mice.
Blocked the antihyperalgesic effect by the CB1 antagonist rimonabant (HY-14136), but not by the CB2 antagonist SR144528 (HY-13439). |
CB2: 50.7 nM (EC50); CB1: 16.1 μM (EC50)
![1-(2,3-DICHLOROBENZOYL)-5-METHOXY-2-METHYL-3-[2-(4-MORPHOLINYL)ETHYL]-1H-INDOLE Structure](/CAS/GIF/180002-83-9.gif)