R B Raffa1, S J Ward. 1. Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA 19140, USA. robert.raffa@temple.edu
Abstract
WHAT IS KNOWN AND OBJECTIVE: The potential beneficial therapeutic effects of cannabinoid CB₁ 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 CB₁ 'selective' and produce their effects exclusively via CB₁ receptors. METHODS: A literature search was conducted of preclinical publications containing information about non-CB₁ 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 CB₁-independent pharmacological actions. We highlight the evidence regarding effects produced in cells lacking CB₁ receptors, effects on neuronal membranes from CB₁ receptor-deficient mutant KO 'knockout' mice and affinity for μ-opioid receptors. WHAT IS NEW AND CONCLUSION: CB₁ 'selective' antagonists and partial agonists have been studied for their anorexigenic and other potential therapeutic uses. An awareness of CB₁-independent mechanism(s) of these agents might contribute to a better understanding of the pharmacologic and toxicologic profiles of these agents.
WHAT IS KNOWN AND OBJECTIVE: The potential beneficial therapeutic effects of cannabinoid CB₁ 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 CB₁ 'selective' and produce their effects exclusively via CB₁ receptors. METHODS: A literature search was conducted of preclinical publications containing information about non-CB₁ 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 CB₁-independent pharmacological actions. We highlight the evidence regarding effects produced in cells lacking CB₁ receptors, effects on neuronal membranes from CB₁ receptor-deficient mutant KO 'knockout' mice and affinity for μ-opioid receptors. WHAT IS NEW AND CONCLUSION: CB₁ 'selective' antagonists and partial agonists have been studied for their anorexigenic and other potential therapeutic uses. An awareness of CB₁-independent mechanism(s) of these agents might contribute to a better understanding of the pharmacologic and toxicologic profiles of these agents.
Authors: Kathryn A Seely; Lisa K Brents; Lirit N Franks; Maheswari Rajasekaran; Sarah M Zimmerman; William E Fantegrossi; Paul L Prather Journal: Neuropharmacology Date: 2012-07-04 Impact factor: 5.250
Authors: Susan M Krzysik-Walker; Isabel González-Mariscal; Morten Scheibye-Knudsen; Fred E Indig; Michel Bernier Journal: Mol Pharmacol Date: 2012-10-12 Impact factor: 4.436
Authors: Charles W Schindler; Maria Scherma; Godfrey H Redhi; Subramanian K Vadivel; Alexandros Makriyannis; Steven R Goldberg; Zuzana Justinova Journal: Psychopharmacology (Berl) Date: 2016-01-23 Impact factor: 4.530
Authors: Zachary W Reichenbach; Kelly DiMattio; Suren Rajakaruna; David Ambrose; William D Cornwell; Ronald J Tallarida; Thomas Rogers; Lee-Yuan Liu-Chen; Ronald F Tuma; Sara Jane Ward Journal: Front Pharmacol Date: 2022-04-21 Impact factor: 5.988