Cannabinoid CB2 receptor agonist activity in the hindpaw incision model of postoperative pain.
The identification of peripherally expressed CB2 receptors and reports that the selective activation of cannabinoid CB2 receptors produces antinociception without traditional cannabinergic side effects suggests that selective cannabinoid CB2 receptor agonists might be useful in the management of pain. In a rat hindpaw incision model, we examined the antiallodynic activity of the selective cannabinoid CB2 receptor agonists AM1241 (3-30 mg/kg i.p.), GW405833 (3-30 mg/kg i.p.), and HU-308 (0.3-30 mg/kg i.p.). The rank order for efficacy in the hindpaw incision model following a dose of 10 mg/kg, i.p. was AM1241 > GW405833 = HU-308, and the selective cannabinoid CB2 receptor antagonist, SR144528, reversed the antiallodynic effect of HU-308. Together, these data suggest that selective cannabinoid CB2 receptor agonists might represent a new class of postoperative analgesics.
LaBuda
Christopher J
CJ
Adolor Corporation, Department of Pharmacology, 700 Pennsylvania Drive, Exton, PA 19341, USA. clabuda@adolor.com
Koblish
Michael
M
Little
Patrick J
PJ
D000818:Animals; D001892:Camphanes / Q000008:administration & dosage / Q000627:therapeutic use; D002186:Cannabinoids / Q000008:administration & dosage / Q000627:therapeutic use; D004334:Drug Administration Schedule; D018409:Foot Injuries / Q000601:surgery; D006614:Hindlimb / Q000601:surgery*; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D023421:Models, Animal; D009025:Morpholines / Q000008:administration & dosage / Q000627:therapeutic use; D010146:Pain / Q000517:prevention & control; D010147:Pain Measurement / Q000379:methods; D010149:Postoperative Pain / Q000503:physiopathology / Q000517:prevention & control*; D011720:Pyrazoles / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000037:antagonists & inhibitors; D013997:Time Factors
C463040:1-(2,3-dichlorobenzoyl)-5-methoxy-2-methyl-(2-(mopholin-4-yl)ethyl)-1H-indole; C439263:AM 1241; D001892:Camphanes; D002186:Cannabinoids; D007211:Indoles; D009025:Morpholines; D011720:Pyrazoles; D043885:Receptor, Cannabinoid, CB2; C110630:SR 144528; C402416:HU 308