Effects of RS-2232, a potential antidepressant, on the levels of monoamines, precursor amino acids and their related metabolites in mouse brain.

Abstract

Abstract-The effects of RS-2232, a new antidepressant, on the levels of mono amines, precursor amino acids and their related metabolites in mouse brain were investigated and compared with some clinically effective antidepressants. RS 2232 (3, 10 and 30 mg/kg, p.o.) increased the levels of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) dose-dependently, 60 min after administration. Tyrosine (TYR) levels were not changed, but tryptophan (TRP) was significantly increased by 20% at 30 mg/kg of the compound. On the other hand, DA metabolites such as 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were significantly reduced at all doses. 5-Hydroxy indoleacetic acid (5-HIAA), a 5-HT metabolite, was decreased by 32% at 10 mg/kg. These changes caused by RS-2232 administration were similar to those of the classical inhibitor of monoamine oxidase (MAO), isocarboxazid (ISO), but rather different from those of imipramine (IMP) and mianserin (MIA). RS-2232 and

Comparative Studies of the Effects of RS-8359 and Safrazine on Monoamine Oxidase In-vitro and In-vivo in Mouse Brain

“…Recently, we have reported that RS-2232,4-(4-cyanophenyl)amino-6,7-dihydro-5H-cyclopenta[d]pyrimidine, caused the dose-dependent accumulation of NA, DA and 5-HT in the mouse brain following its acute administration (Yokoyama et al 1987a). This effect of RS-2232 was proved to be produced by the reversible and specific inhibition of MAO-A in mouse brain (Yokoyama et a1 1987b).…”