The Role of the Cannabinoid CB2 Receptor in Pain Transmission and Therapeutic Potential of Small Molecule CB2 Receptor Agonists

G   T.   Whiteside; G.   P.   Lee; K   J.   Valenzano

Abstract

This review gives a brief overview of the expression patterns, molecular pharmacology and physiological role of the cannabinoid 2 receptor (CB2) in pain. Particular emphasis is given to the therapeutic utility of CB2 receptor agonists. Through studies utilizing selective CB2 receptor agonists, non-selective cannabinoid agonists in conjunction with selective CB1 and CB2 receptor antagonists, or CB2 receptor knockout mice, it is now clear that this receptor plays a critical role in nociception. To this end, CB2 receptors have been shown to modulate acute pain, chronic inflammatory pain, post-surgical pain, cancer pain and pain associated with nerve injury. Here we review these studies and the compounds that were utilized. We hypothesize the mechanism of action by which the CB2 receptor could be involved in these processes. Finally we summarize the most recent novel chemical scaffolds that are being investigated towards advancing selective CB2 receptor agonists into the clinic. Many new pharmacological agents have been identified by high throughput screening and small molecule lead discovery and optimization in the past 10 years. It is anticipated that at least some of these agents may ultimately constitute effective new pain therapeutics that lack the side effects associated with traditional cannabinoid ligands.

Keywords: Cannabinoid, CB2, receptor, pain, inflammation, neuropathic

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Current Medicinal Chemistry

Title: The Role of the Cannabinoid CB2 Receptor in Pain Transmission and Therapeutic Potential of Small Molecule CB2 Receptor Agonists

Volume: 14 Issue: 8

Author(s): G T. Whiteside, G. P. Lee and K J. Valenzano

Affiliation:

Keywords: Cannabinoid, CB2, receptor, pain, inflammation, neuropathic

Abstract: This review gives a brief overview of the expression patterns, molecular pharmacology and physiological role of the cannabinoid 2 receptor (CB2) in pain. Particular emphasis is given to the therapeutic utility of CB2 receptor agonists. Through studies utilizing selective CB2 receptor agonists, non-selective cannabinoid agonists in conjunction with selective CB1 and CB2 receptor antagonists, or CB2 receptor knockout mice, it is now clear that this receptor plays a critical role in nociception. To this end, CB2 receptors have been shown to modulate acute pain, chronic inflammatory pain, post-surgical pain, cancer pain and pain associated with nerve injury. Here we review these studies and the compounds that were utilized. We hypothesize the mechanism of action by which the CB2 receptor could be involved in these processes. Finally we summarize the most recent novel chemical scaffolds that are being investigated towards advancing selective CB2 receptor agonists into the clinic. Many new pharmacological agents have been identified by high throughput screening and small molecule lead discovery and optimization in the past 10 years. It is anticipated that at least some of these agents may ultimately constitute effective new pain therapeutics that lack the side effects associated with traditional cannabinoid ligands.

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Whiteside T. G, Lee P. G. and Valenzano J. K, The Role of the Cannabinoid CB2 Receptor in Pain Transmission and Therapeutic Potential of Small Molecule CB2 Receptor Agonists, Current Medicinal Chemistry 2007; 14 (8) . https://dx.doi.org/10.2174/092986707780363023

DOI https://dx.doi.org/10.2174/092986707780363023	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X

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