THE APPETITE-SUPPRESSANT D-FENFLURAMINE INDUCES APOPTOSIS IN HUMAN SEROTONERGIC CELLS

FENFLURAMINE is an amphetamine analogue which has been widely used in the treatment of obesity. In rodents, non-human primates, and humans, fenfluramine is associated with some indices of neurotoxicity, as well as pulmonary hypertension and cardiac valve pathology. In the present study, d-fenfluramine was found to be cytotoxic to the serotonin (5-H T) transporter (5-HTT) expressing human placental choriocarcinoma cell s. d-Fenfluramine caused DNA fragmentation and apoptosis. Apoptosis wa s not observed after the 5-HTT had been blocked by fluoxetine, indicat ing that intact 5-HTT function is required for d-fenfluramine to induc e programmed cell death. These observations in a human cell line may r eflect a possible mechanism associated with the risks of fenfluramine administration in several species, including humans. NeuroReport 9: 29 89-2993 (C) 1998 Lippincott Williams & Wilkins.