Metabolic consequences of fenfluramine for the control of body weight

The chronic ingestion of fenfluramine results in a sustained depression in body weight despite the return of ad libitum food intake to normal levels. This chronic suppression of body weight is immediately reversed after discontinuation of the drug treatment. Such a phenomenon indicates that the drug must increase metabolic rate. However, studies in both humans and animals have failed to demonstrate an increase in metabolic rate after the administration of the drug. Instead, fenfluramine appears to potentiate the expenditure of energy whenever increases in energy expenditure occur. Fenfluramine potentiates the thermic effect of food (TEF) both in animals as well as in humans. Moreover, the energy cost of locomotor behavior also appears to be potentiated by this drug. Most importantly from a therapeutic perspective, unlike the anorectic effect of fenfluramine, tolerance does not appear to develop to its ability to potentiate energy expenditure.