Deamination of norepinephrine, dopamine, and serotonin by type A monoamine oxidase in discrete regions of the rat brain and inhibition by RS-8359.
Levels of monoamines and their metabolites were determined in the cortex, hippocampus, and striatum of rats killed by microwave irradiation. Moclobemide (20 mg/kg, p.o.) and clorgyline (10 mg/kg, p.o.), type A monoamine oxidase (MAO-A) inhibitors, increased the levels of normetanephrine (NM) and 3-methoxytyramine (3MT) and decreased those of 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5HIAA) in almost all three regions. Deprenyl (10 mg/kg, p.o.), a type B monoamine oxidase inhibitor, however, little affected monoamine and metabolite levels in all regions. The maximum effects of RS-8359 (10 mg/kg, p.o.) were obtained at 2 to 6 hr after administration, when the levels of norepinephrine (NE), NM, 3MT, and serotonin (5HT) in all regions and dopamine (DA) in the striatum increased, while DOPAC and HVA levels decreased. The levels of monoamines and metabolites had returned to normal by 20 hr after administration. Dose-dependency of the effects of RS-8359 on monoamine metabolites was observed at doses up to 30 mg/kg (p.o.) at 1 and 6 hr after administration. In conclusion, NE, DA, and 5HT are exclusively or preferentially deaminated by MAO-A in the cortex, hippocampus, and striatum of rats, and RS-8359 exhibits a reversible MAO-A inhibitory action in all three regions tested in vivo.
Kumagae
Y
Y
Biological Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Matsui
Y
Y
Iwata
N
N
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D003010:Clorgyline / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D003641:Deamination / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D020912:Moclobemide; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012642:Selegiline / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism
D001549:Benzamides; D015306:Biogenic Monoamines; D008996:Monoamine Oxidase Inhibitors; D009570:Nitriles; D011743:Pyrimidines; D012642:Selegiline; D012701:Serotonin; C059590:RS 8359; D008995:Monoamine Oxidase; D003010:Clorgyline; D020912:Moclobemide; D004298:Dopamine; D009638:Norepinephrine