Targeting cannabinoid agonists for inflammatory and neuropathic pain

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Expert Opin Investig Drugs. 2007 Jul;16(7):951-65.

Targeting cannabinoid agonists for inflammatory and neuropathic pain.

Cheng Y, Hitchcock SA.

Amgen, Inc., Chemistry Research and Development, MS 29-2-C, Thousand

Oaks, CA 91320, USA.

The cannabinoid receptors CB(1) and CB(2) are class A G-protein-

coupled receptors. It is well known that cannabinoid receptor

agonists produce relief of pain in a variety of animal models by

interacting with cannabinoid receptors. CB(1) receptors are located

centrally and peripherally, whereas CB(2) receptors are expressed

primarily on immune cells and tissues. A large body of preclinical

data supports the hypothesis that either CB(2)-selective agonists or

CB(1) agonists acting at peripheral sites, or with limited CNS

exposure, will inhibit pain and neuroinflammation without side

effects within the CNS. There has been a growing interest in

developing cannabinoid agonists. Many new cannabinoid ligands have

been synthesized and studied covering a wide variety of novel

structural scaffolds. This review focuses on the present development

of cannabinoid agonists with an emphasis on selective CB(2) agonists

and peripherally restricted CB(1) or CB(1)/CB(2) dual agonists for

treatment of inflammatory and neuropathic pain.