title: Some effects of CB1 antagonists with inverse agonist and neutral biochemical properties.
abstract: The CB1 inverse agonist/antagonist SR141716A recently has been introduced for the management of obesity (rimonabant; Acomplia) and appears to have beneficial effects. However, its utility may be hampered in some individuals by adverse effects including nausea or emesis or by mood depression. The recent development of biochemically 'neutral' antagonists such as AM4113 (Sink et al., 2007) has allowed an initial evaluation of the proposition that adverse effects of SR141716A are associated with its inverse agonist activity. Thus far, data comparing SR141716A and AM4113 across several species indicate that both drugs produce dose-related direct effects on operant behavior within the same range of doses that serve to antagonize the behavioral and hypothermic effects of a CB1 agonist. However, initial observations suggest that AM4113 may not produce preclinical indications of nausea or emesis. Further studies with AM4113 and other novel CB1 antagonists differing in efficacy should amplify our understanding of the relationship between the pharmacological activity of CB1 antagonists and their behavioral effects.
authors: McLean Hospital-Harvard Medical School. Belmont MA USA. jbergman@hms.harvard.edu
authors: Jack
authors: J
authors: Bergman
authors: Marcus S
authors: MS
authors: Delatte
authors: Carol A
authors: CA
authors: Paronis
authors: Kiran
authors: K
authors: Vemuri
authors: Ganesh A
authors: GA
authors: Thakur
authors: Alex
authors: A
authors: Makriyannis
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D004347:Drug Interactions; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D000077285:Rimonabant
chemical_list: C529765:AM4113; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077285:Rimonabant