Effect of fenfluramine administration on synaptosomal uptake of some neurotransmitters and on synaptosomal enzymes which metabolise GABA.
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-trasaminase 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).
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000648:ultrastructure; D005277:Fenfluramine / Q000494:pharmacology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D013574:Synaptosomes / Q000201:enzymology / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018377:Neurotransmitter Agents; D005277:Fenfluramine; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase