title: CB₁-independent mechanisms of Δ⁹-THCV, AM251 and SR141716 (rimonabant).
abstract: 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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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: Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA 19140, USA. robert.raffa@temple.edu
authors: R B
authors: RB
authors: Raffa
authors: S J
authors: SJ
authors: Ward
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D001067:Appetite Depressants / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D013759:Dronabinol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008024:Ligands; D010880:Piperidines / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D011720:Pyrazoles / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077285:Rimonabant
chemical_list: D019440:Anti-Obesity Agents; D001067:Appetite Depressants; D008024:Ligands; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D017450:Receptors, Opioid, mu; C003403:tetrahydrocannabivarin 9; C103505:AM 251; D013759:Dronabinol; D000077285:Rimonabant