Effect of Fenfluramine on Appetite and Lipid Metabolism of the Young Ruminant

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Abstract
Eight Ito)stein calves were used in two 4 × 4 Latin square experiments to deter- mine the action of fenfluramine (N-ethyl-3- trifiuoromethylphenethylamine) at five daily oral doses of 0, 5, 10 and 20 mg per kg bodyweight on appetite, blood lipids and glucose. Subsequently, eight additional calves were fasted for eight days and used to determine the effect of fenfluramine in fasted calves. Four calves received 10 mg per kg per day of drug while 4 served as controls. Preliminary rumen incubations showed that fenfluramine was stable in the rumen environment and blood serum peaks of fenfluramine within 2 hours following oral dosing suggested rumen absorption of the drug. Dose effected a linear reduction in feed intake which was 50% at 10 mg per kg. Serum free fatty acids were very closely correlated with feed intake, increas- ing linearly with drug concentration but returning to normal in two days after dis- continuing the drug. Fasting alone pro- duced a significant lipolytic response, but some )ipolytic action of drug was present during Days 1 and 2 of fast. In fed calves, all concentrations of drug resulted in simi- lar reductions of triglycerides. In fasted calves, triglycerides for both control and treated groups declined to 60% of base values, but fenfluramine calves returned to base values faster than controls. Serum glucose was reduced for fed calves at all concentrations of drug as well as in fasted control and fasted drug-treated calves, thus suggesting that the plane of nutrition was the important factor. Serum cholesterol was not altered by fenfluramine or fasting. The mechanism of action of fenfluramine in bovine metabolism was discussed.