Dexfenfluramine neurotoxicity in brains of non-human primates.
Dexfenfluramine, a drug prescribed for appetite suppression, was evaluated in non-human primates for its potential to produce toxic effects on brain serotonin (5-HT) neurons. Squirrel monkeys received dexfenfluramine subcutaneously twice daily for four days at doses of 1.25 or 5.00 mg/kg. Two weeks later, a dose-related depletion of 5-HT and 5-hydroxyindoleacetic acid was found, together with a reduced number of 5-HT uptake sites. Morphological studies showed acute pathological changes in 5-HT axons, followed by a persistent decrease in 5-HT axon density. Our findings indicate that dexfenfluramine damages central 5-HT neurons in monkeys and raise concern about the potential neurotoxicity of this drug in man.
Ricaurte
G A
GA
Department of Neurology, Francis Scott Key Medical Center, Johns Hopkins School of Medicine, Baltimore, Maryland 21224.
Molliver
M E
ME
Martello
M B
MB
Katz
J L
JL
Wilson
M A
MA
Martello
A L
AL
D000818:Animals; D001369:Axons / Q000187:drug effects; D001923:Brain Chemistry; D002421:Caudate Nucleus / Q000737:chemistry; D002540:Cerebral Cortex / Q000737:chemistry; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D005277:Fenfluramine / Q000008:administration & dosage / Q000009:adverse effects* / Q000032:analysis; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D008297:Male; D009474:Neurons / Q000187:drug effects*; D012453:Saimiri; D012701:Serotonin / Q000032:analysis; D013788:Thalamus / Q000737:chemistry
D005277:Fenfluramine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid