Abstract
Summary
Fenfluramine and its N-demethyl metabolite, norfenfluramine (3-tri-fluoromethyl-amphetamine), lowered brain serotonin, 5-hydroxyindoleacetic acid, and tryptophan hydroxylase in rats acutely and the effect persisted for more than 1 week after a single ip dose of the drugs. Serotonin depletion by fenfluramine and norfenfluramine was blocked by pretreatment with fluoxetine, an inhibitor of uptake into serotonin neurons. Serotonin turnover, as measured by the rate of 5-hydroxyindoleacetic acid accumulation after probenecid administration, was decreased significantly still at 1 week after fenfluramine administration. The effects of fenfluramine and norfenfluramine on brain serotonin neurons in rats resemble those of p-chloroamphetamine and probably occur via similar mechanisms.
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