RS-2232, a compound with a reversible and specific type-A monoamine oxidase inhibiting property in mouse brain.
Effects of RS-2232 on monoamine oxidase (MAO) activities in mouse brain and liver were investigated with 5-hydroxytryptamine (5-HT), beta-phenyl-ethylamine (PEA), and in some cases, kynuramine as substrate. IC50s of RS-2232 for 5-HT (100 microM) and PEA (20 microM) deaminations in brain mitochondrial preparations were 0.14 microM and 52 microM, respectively. RS-2232 was found to be a competitive inhibitor of 5-HT deamination in the preparation, and its Ki was 0.054 microM. The inhibitions of MAO in both brain and liver homogenate by RS-2232 in vitro measured with kynuramine (100 microM) were independent of the prolonged preincubation. 5-HT deaminations in the brain homogenates of mice treated with RS-2232 were decreased significantly by 15% and 59% at 10 and 30 mg/kg (p.o.) of the compound, respectively. On the other hand, PEA deaminations were not changed at the same doses. Pressor responses induced by intravenous tyramine (0.1-1.0 mg/kg) in anesthetized rats was little affected by oral administration of RS-2232 (3-30 mg/kg) once daily for two weeks. These results reveal that RS-2232 has a reversible and specific type-A MAO inhibiting property in mouse brain, and they suggest that RS-2232 is relatively safe in tyramine-potentiation.
Yokoyama
T
T
Biological Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Iwata
N
N
Kobayashi
T
T
D000758:Anesthesia; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000201:enzymology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D014439:Tyramine / Q000494:pharmacology
D000928:Antidepressive Agents; D008996:Monoamine Oxidase Inhibitors; D011743:Pyrimidines; C054329:RS 2232; D008995:Monoamine Oxidase; D014439:Tyramine