The Anorectic Properties of Opiate Antagonists

The effects of six opiate antagonists (naloxone, naltrexone, diprenorphine, Mr 1452, Mr 2266, and WIN 44,441) were studied on the food intake of food-deprived rats. The potencies of these agents in standard tests of opiate antagonism were also measured. With the exception of WIN 44,441, all opiate antagonists reduced food consumption. However, all the active drugs had similar potencies in producing this effect whereas they had very different potencies in antagonizing the effects of opiates in vivo and in vitro. Furthermore, the anorectic action of the opiate antagonists differed in several respects from the effects produced by fenfluramine and diethylpropion. These results are consistent with a role for endogenous opioids in the control of appetite but suggest that the mechanisms involved may differ from those concerned in other opioid functions and from those mediating the actions of other anorectic drugs.