Effects of RS-2232, a Potential Antidepressant, on the Levels of Monoamines, Precursor Amino Acids and Their Related Metabolites in Mouse Brain

Abstract

The effects of RS-2232, a new antidepressant, on the levels of monoamines, 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 ISO antagonized against reserpine (2 mg/kg, s.c.)-induced changes in the contents of monoamines and their metabolites. Furthermore, time-course experiments clearly showed that increase in the levels of monoamines by 10 mg/kg of RS-2232 was restored to the control levels within a few hours. These results suggest that RS-2232 has reversible MAO inhibiting properties in vivo in mouse brain.