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-HT) transporter (5-HTT) expressing human placental choriocarcinoma cells. d-Fenfluramine caused DNA fragmentation and apoptosis. Apoptosis was not observed after the 5-HTT had been blocked by fluoxetine, indicating that intact 5-HTT function is required for d-fenfluramine to induce programmed cell death. These observations in a human cell line may reflect a possible mechanism associated with the risks of fenfluramine administration in several species, including humans.
Bengel
D
D
Section on Clinical Neuropharmacology, Laboratory of Clinical Science, NIMH, NIH Clinical Center, Bethesda, MD 20892, USA.
Isaacs
K R
KR
Heils
A
A
Lesch
K P
KP
Murphy
D L
DL
D017209:Apoptosis / Q000187:drug effects*; D001067:Appetite Depressants / Q000633:toxicity*; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002822:Choriocarcinoma; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005277:Fenfluramine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005473:Fluoxetine / Q000494:pharmacology; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000633:toxicity; D050486:Serotonin Plasma Membrane Transport Proteins; D013997:Time Factors; D014407:Tumor Cells, Cultured
D001067:Appetite Depressants; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D018490:Serotonin Agents; D050486:Serotonin Plasma Membrane Transport Proteins; D005473:Fluoxetine; D005277:Fenfluramine; D012701:Serotonin