Effect of repeated amiflamine administration on serotonergic and noradrenergic neurotransmission: electrophysiological studies in the rat CNS.

Amiflamine is a selective and reversible inhibitor of monoamine oxidase (MAO) type A which exerts a preferential effect on serotonin (5-HT) catabolism. The present studies were undertaken to compare the effects of repeated administration of amiflamine (2 mg/kg, twice daily) on several aspects of the functioning of the 5-HT and norepinephrine (NE) systems in the rat CNS. The activity of MAO-A and B was assessed in forebrain slices and the whole brain contents of the neurotransmitters and their metabolites were determined by HPLC after 2-, 7- and 21-day treatments. MAO-A was inhibited by about 50% 2 h after the last dose and its activity was back to normal in rats sacrificed 12 h after the last dose. The activity of MAO-B was unaffected two or 12 h after the last dose. Whole brain concentration of 5-HT was increased to a greater degree than that of NE following repeated administration of amiflamine. These increases in 5-HT and NE were accompanied by decreased levels of their respective metabolites 5-hydroxy-indoleacetic acid and 3-methoxy-4-hydroxyphenylethyleneglycol. The firing activity of dorsal raphe 5-HT neurons, but not that of NE neurons, was markedly decreased 2-6 h after the last dose of a 2-day treatment. However, 2-6 h after a 21-day treatment, the firing activity of 5-HT neurons was back to normal, whereas that of NE neurons was decreased by 30%.(ABSTRACT TRUNCATED AT 250 WORDS)