title: Comparative serotonin neurotoxicity of the stereoisomers of fenfluramine and norfenfluramine.
abstract: The optical isomers of fenfluramine and norfenfluramine were administered to rats to examine their relative potency for destruction of serotonin neurons. Rats were sacrificed one week following a single 10 mg/kg SC injection of one of the four compounds and monoamine and metabolite levels in the frontal cortex and hippocampus brain regions were examined by HPLC-EC techniques. In addition, [3H]-paroxetine binding to homogenates of these brain regions was determined. With the exception of hippocampal 5-HT levels following d-fenfluramine treatment, there was a decrease in all the serotonergic markers assayed, following treatment with the d-enantiomers of fenfluramine and norfenfluramine. No decrease in any serotonergic marker was seen at this dose following treatment with the l-enantiomers of fenfluramine or norfenfluramine. Also, none of the drug treatments resulted in a significant decrease in catecholamines or their metabolites. With all the serotonergic markers examined, d-norfenfluramine was found to cause a significantly greater decrease than d-fenfluramine. The significance of these results is discussed in terms of the hypothesis that the long-term serotonergic deficits observed with d-fenfluramine may result from its metabolite, d-norfenfluramine.
authors: Department of Pharmacology, Purdue University, West Lafayette, IN 47907.
authors: M P
authors: MP
authors: Johnson
authors: D E
authors: DE
authors: Nichols
mesh_terms: D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D005277:Fenfluramine / Q000031:analogs & derivatives* / Q000633:toxicity*; D005625:Frontal Lobe / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects*; D009642:Norfenfluramine / Q000633:toxicity*; D017374:Paroxetine; D010880:Piperidines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D015306:Biogenic Monoamines; D010880:Piperidines; D009642:Norfenfluramine; D005277:Fenfluramine; D012701:Serotonin; D017374:Paroxetine