The mechanism of action of fenfluramine

S. Garattini, W. Buczko, A. Jori, R. Samanin

Research output: Contribution to journalArticlepeer-review


Fenfluramine and amphetamine exert different actions on central biogenic amines. Neither drug alters the concentration of dopamine (DA) in the rat striatum but both drugs increase striatal homovanillic acid levels with opposite stereoisomeric specificity and by different mechanisms. The evidence presented suggests that fenfluramine blocks the DA receptors, whereas amphetamine acts indirectly presynaptically to stimulate the release of DA from dopaminergic terminals. Thus a similar biochemical effect is achieved by completely opposite mechanisms. Neither fenfluramine nor amphetamine change the concentration of acetylcholine in whole brain. Fenfluramine and norfenfluramine though not amphetamine lower brain 5 hydroxy tryptamine (5HT) and 5 hydroxy indole acetic acid. The results with fenfluramine on release and uptake of 14C 5HT in platelets suggest that this drug acts on 5HT stores by 2 different mechanisms, these being a release of 5HT and inhibition of 5HT uptake. The results of brain amine manipulations on the anorectic actions of fenfluramine and amphetamine suggest that these two drugs induce anorexia in animals by different mechanisms. An intact serotonergic system appears to be necessary to permit fenfluramine anorexia by a release of 5HT, whilst the catecholaminergic pathways appear to be involved in amphetamine anorexia.

Original languageEnglish
Pages (from-to)27-35
Number of pages9
JournalPostgraduate Medical Journal
Issue numberSup.1
Publication statusPublished - 1975

ASJC Scopus subject areas

  • Medicine(all)


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