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)
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology*; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*
D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; D012701:Serotonin; D000109:Acetylcholine; C031466:amiflamine; D009638:Norepinephrine