Effect of phenylpiperidine opioid antagonists on food consumption and weight gain of the obese Zucker rat.

Meal-fed Zucker rats were used to determine the acute and chronic s.c. effect of certain trans-3,4-dimethyl-4-phenylpiperidines (opioid antagonists) on food consumption. In acute studies, the active compounds suppressed food intake significantly of lean and obese meal-fed Zucker rats. LY117413 was the most effective over the 4-hr period immediately after the s.c. administration of the drug. Long-term chronic s.c. administration to the meal-fed obese Zucker rat showed that LY88329 and LY117413 significantly reduced food consumption for as long as the drug was administered and resulted in a significant decrease in body weight gain when compared to nontreated control obese rats. There was no evidence for the development of tolerance to these effects of LY88329 and LY117413 in this genetically obese rat model.