Effects of fenfluramine on accumulation of 5-hydroxytryptamine and other neurotransmitters into synaptosomes of rat brain.

Earlier studies have demonstrated a marked long-lasting reduction in the brain level of 5-hydroxytryptamine after injection of fenfluramine. The decrease in the brain levels of dopamine and noradrenaline were less marked and disappeared one day after treatment. In this study, the effects of fenfluramine upon the uptake of 5-hydroxytryptamine and other neurotransmitters (dopamine, γ-aminobutyric acid) or their precursors (tryptophan, tyrosine and glutamic acid) into synaptosomes of rat brain were investigated. In vivo, fenfluramine is a competitive inhibitor of the high affinity synaptosomal uptake of 5-hydroxytryptamine. Even though fenfluramine produced a small reduction in the uptake of dopamine, γ-aminobutyric and glutamic acids 4 hr after injection, this effect disappeared 1 day later. In vitro, addition of fenfluramine into a synaptosomal fraction reduced uptake of 5-hydroxytryptamine, dopamine, γ-aminobutyric acid, glutamic acid, tryptophan and tjrosine. [¹⁴C] Fenfluramine itself was bound to synaptosomes. Ten days after 5–6 dihydroxytryptamine treatment, both the accumulation of [¹⁴C] fenfluramine in the brain in vivo, and the binding of [¹⁴C] fenfluramine to synaptosomes in vitro, were reduced. These results indicate that 5-hydroxytryptamine synaptosomal sites are involved in some actions of fenfluramine.