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

Eight Holstein calves were used in two 4×4 Latin square experiments to determine the action of fenfluramine (N-ethyl-3-trifluoromethylphenethylamine) at five daily oral doses of 0, 5, 10 and 20mg 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 10mg 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 10mg per kg. Serum free fatty acids were very closely correlated with feed intake, increasing linearly with drug concentration but returning to normal in two days after discontinuing the drug. Fasting alone produced a significant lipolytic response, but some lipolytic action of drug was present during Days 1 and 2 of fast. In fed calves, all concentrations of drug resulted in similar 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.