Summary
Fenfluramine has been considered to deplete neuronal 5-hydroxytryptamine (5-HT). This compound is able to reduce the synaptosomal uptake of 5-HT and other neurotransmitters such as GABA and glutamic acid (Glu). The effects of fenfluramine on these three compounds considered as neurotransmitters are different. The inhibition is of competitive type for 5-HT and non-competitive for GABA and Glu. Concerning the enzymes involved in GABA synthesis and degradation, Fenfluramine increases Glutamic acid decarboxylase activity and decreases GABA-transaminase activity in synaptosomes. Decreased synaptosomal GABA levels could be attributed to a lower uptake. An enzymatic regulating system may be responsible in restoring the GABA level. A similar mechanism concerning serotonin has been previously suggested (Costa et al., 1971).
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Kouyoumdjian, J.C., Gonnard, P. & Belin, M.F. Effect of fenfluramine administration on synaptosomal uptake of some neurotransmitters and on synaptosomal enzymes which metabolise GABA. Naunyn-Schmiedeberg's Arch. Pharmacol. 309, 7–11 (1979). https://doi.org/10.1007/BF00498750
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DOI: https://doi.org/10.1007/BF00498750