CB 1-independent mechanisms of Δ 9-THCV, AM251 and SR141716 (rimonabant)

Abstract

What is known and Objective: The potential beneficial therapeutic effects of cannabinoid CB 1 receptor antagonists or partial agonists have driven drug discovery and development efforts and have led to clinical candidates. It is generally assumed that these compounds are CB 1'selective' and produce their effects exclusively via CB 1 receptors. Methods: A literature search was conducted of preclinical publications containing information about non-CB 1 receptor pharmacology of these agents. The information was summarized and evaluated from the perspective of contribution to a fuller understanding of this aspect of these compounds. Results and Discussion: A number of recent studies have revealed that these compounds have CB 1-independent pharmacological actions. We highlight the evidence regarding effects produced in cells lacking CB 1 receptors, effects on neuronal membranes from CB 1 receptor-deficient mutant KO 'knockout' mice and affinity for μ-opioid receptors. What is new and Conclusion: CB 1'selective' antagonists and partial agonists have been studied for their anorexigenic and other potential therapeutic uses. An awareness of CB 1-independent mechanism(s) of these agents might contribute to a better understanding of the pharmacologic and toxicologic profiles of these agents. © 2011 Blackwell Publishing Ltd.