Targeting cannabinoid agonists for inflammatory and neuropathic pain.
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.
Cheng
Yuan
Y
Amgen, Inc., Chemistry Research and Development, MS 29-2-C, Thousand Oaks, CA 91320, USA. yuanc@amgen.com
Hitchcock
Stephen A
SA
D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015507:Drugs, Investigational; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000188:drug therapy; D009437:Neuralgia / Q000175:diagnosis / Q000188:drug therapy*; D009443:Neuritis / Q000175:diagnosis / Q000188:drug therapy; D010147:Pain Measurement; D010148:Intractable Pain / Q000175:diagnosis / Q000188:drug therapy*; D011446:Prospective Studies; D051381:Rats; D043885:Receptor, Cannabinoid, CB2 / Q000187:drug effects*; D011955:Receptors, Drug / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D018570:Risk Assessment; D012680:Sensitivity and Specificity
D000700:Analgesics; D002186:Cannabinoids; D015507:Drugs, Investigational; D043885:Receptor, Cannabinoid, CB2; D011955:Receptors, Drug