Synergistic effects of cannabinoid inverse agonist AM251 and opioid antagonist nalmefene on food intake in mice.
Oral administration of the opioid antagonist nalmefene alone (up to 20 mg/kg) failed to show a significant effect on acute food intake in mice. However, combined oral dosing of nalmefene and subthreshold doses of AM251, a cannabinoid CB1 receptor inverse agonist, led to a significant reduction in food intake in both lean and diet-induced obese (DIO) mice. Furthermore, the anorectic effect of a high dose of AM251 was further enhanced when co-administered with nalmefene. The results support a synergistic interaction between opioid and cannabinoid systems in regulating feeding behavior.
Chen
Richard Z
RZ
Department of Metabolic Disorders, PO Box 2000, RY80M-213, Rahway, NJ 07065, USA. richard_z_chen@merck.com
Huang
Ruey-Ruey C
RR
Shen
Chun-Pyn
CP
MacNeil
Douglas J
DJ
Fong
Tung M
TM
D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects* / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism; D002186:Cannabinoids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D018847:Opioid Peptides / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects* / Q000378:metabolism
D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C103505:AM 251; D009271:Naltrexone; C038981:nalmefene