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Brain Res. 2004 Mar 5;999(2):227-30.

Synergistic effects of cannabinoid inverse agonist AM251 and opioid antagonist nalmefene on food intake in mice.

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  • 1Department of Metabolic Disorders, PO Box 2000, RY80M-213, Rahway, NJ 07065, USA.


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.

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