当前位置： SCI文献检索 > BRITISH JOURNAL OF PHARMACOLOGY期刊下所有文献 > In vitro and in vivo characterization of A-796260: a selective cannabinoid CB2 receptor agonist exhibiting analgesic activity in rodent pain models.

In vitro and in vivo characterization of A-796260: a selective cannabinoid CB2 receptor agonist exhibiting analgesic activity in rodent pain models.

Abstract：

BACKGROUND AND PURPOSE:Selective cannabinoid CB2 receptor agonists have demonstrated analgesic activity across multiple preclinical pain models. AM1241 is an indole derivative that exhibits high affinity and selectivity for the CB2 binding site and broad spectrum analgesic activity in rodent models, but is not an antagonist of CB2 in vitro functional assays. Additionally, its analgesic effects are mu-opioid receptor-dependent. Herein, we describe the in vitro and in vivo pharmacological properties of A-796260, a novel CB2 agonist. EXPERIMENTAL APPROACH:A-796260 was characterized in radioligand binding and in vitro functional assays at rat and human CB1 and CB2 receptors. 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, CB2 and mu-opioid receptor antagonists. KEY RESULTS:A-796260 exhibited high affinity and agonist efficacy at human and rat CB2 receptors, and was selective for the CB2 vs CB1 subtype. Efficacy in models of inflammatory, post-operative, neuropathic and OA pain was demonstrated, and these activities were selectively blocked by CB2, but not CB1 or mu-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 CB2 receptor-selective agonists for the treatment of pain. In addition, they demonstrate that A-796260 may be a useful new pharmacological compound for further studying CB2 receptor pharmacology and for evaluating its role in the modulation of pain.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Yao BB,Hsieh GC,Frost JM,Fan Y,Garrison TR,Daza AV,Grayson GK,Zhu CZ,Pai M,Chandran P,Salyers AK,Wensink EJ,Honore P,Sullivan JP,Dart MJ,Meyer MD

doi

10.1038/sj.bjp.0707568

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

390-401

issue

eissn

0007-1188

issn

1476-5381

pii

0707568

journal_volume

153

pub_type

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In vitro and in vivo characterization of A-796260: a selective cannabinoid CB2 receptor agonist exhibiting analgesic activity in rodent pain models.