Is receptor activation involved in the mechamism by which (+)-fenfluramine and (+)-norfenfluramine deplete 5-hydroxytryptamine in the rat brain?

R. Invernizzi, K. Kmieciak-Kolada, R. Samanin

Research output: Contribution to journalArticlepeer-review

Abstract

The effects of (+)-fenfluramine, (+)-norfenfluramine and reserpine on the concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in brainstem and telencephalon were studied in rats treated with methergoline, a 5-HT antagonist. Methergoline significantly reduced the effect of (+)-norfenfluramine (5 mg/kg) on 5-HT levels in telencephalon and brainstem but did not modify the effect of (+)-norfenfluramine (2.5 mg/kg). Neither the effect of (+)-fenfluramine on 5-HT levels nor the decrease of 5-HT metabolism caused by (+)-fenfluramine and (+)-norfenfluramine was significantly modified by methergoline treatment. Methergoline potentiated the effects of reserpine on brain indoles. The effect was particularly evident on 5-HIAA levels in the brainstem, although significant effects were found on 5-HT in the brainstem and 5-HIAA in the telencephalon depending on the dose of reserpine used. The results show that postsynaptic receptor activation may partially contribute to the depletion of brain 5-HT caused by (+)-norfenfluramine in the rat. This mechanism does not seem to play a significant role in the effect of (+)-fenfluramine.

Original languageEnglish
Pages (from-to)525-530
Number of pages6
JournalBritish Journal of Pharmacology
Volume75
Issue number3
Publication statusPublished - 1982

ASJC Scopus subject areas

  • Pharmacology

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