In vitroandin vivocharacterization of A‐796260: a selective cannabinoid CB2receptor agonist exhibiting analgesic activity in rodent pain models

Publisher Website
Google Scholar
Abstract
Background and purpose: Selective cannabinoid CB2receptor agonists have demonstrated analgesic activity across multiple preclinical pain models. AM1241 is an indole derivative that exhibits high affinity and selectivity for the CB2binding site and broad spectrum analgesic activity in rodent models, but is not an antagonist of CB2in vitrofunctional assays. Additionally, its analgesic effects are μ‐opioid receptor‐dependent. Herein, we describe thein vitroandin vivopharmacological properties of A‐796260, a novel CB2agonist.Experimental approach: A‐796260 was characterized in radioligand binding andin vitrofunctional assays at rat and human CB1and CB2receptors. The behavioural profile of A‐796260 was assessed in models of inflammatory, post‐operative, neuropathic, and osteoarthritic (OA) pain, as well as its effects on motor activity. The receptor specificity was confirmed using selective CB1, CB2and μ‐opioid receptor antagonists.Key results: A‐796260 exhibited high affinity and agonist efficacy at human and rat CB2receptors, and was selective for the CB2vs CB1subtype. Efficacy in models of inflammatory, post‐operative, neuropathic and OA pain was demonstrated, and these activities were selectively blocked by CB2, but not CB1or μ‐opioid receptor‐selective antagonists. Efficacy was achieved at doses that had no significant effects on motor activity.Conclusions and implications: These results further confirm the therapeutic potential of CB2receptor‐selective agonists for the treatment of pain. In addition, they demonstrate that A‐796260 may be a useful new pharmacological compound for further studying CB2receptor pharmacology and for evaluating its role in the modulation of pain.British Journal of Pharmacology(2008)153, 390–401; doi:10.1038/sj.bjp.0707568; published online 12 November 2007