LONG-TERM TREATMENT OF OBESE ZUCKER RATS WITH LY255582 AND OTHER APPETITE-SUPPRESSANTS

LY255582, administered subcutaneously, decreased food intake and body weight gain of fed obese Zucker rats during the entire 30-day period o f treatment. No tolerance to these biologic effects of LY255582 could be demonstrated. d-Amphetamine and naltrexone, administered subcutaneo usly, and d,l-fenfluramine and salbutamol, administered orally, decrea sed food intake for no more than 6 to 12 days, in contrast to the long -lasting effects of LY255582. Salbutamol suppressed the appetite of ob ese rats for 34 days only. After an additional 12 days of treatment, w eight gain decreased significantly accompanied by no appetite suppress ion. Thus, there is a difference in the duration of action of the opio id antagonist, LY255582, when compared to amphetamine, fenfluramine, n altrexone, and salbutamol, on food intake and body weight gain of obes e rats.