Effects of RS-2232, a potential antidepressant, on the levels of monoamines, precursor amino acids and their related metabolites in mouse brain.
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-Hydroxyindoleacetic 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.
Yokoyama
T
T
Biological Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Kamioka
T
T
Iwata
N
N
Kobayashi
T
T
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001679:Biogenic Amines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D007099:Imipramine / Q000494:pharmacology; D007520:Isocarboxazid / Q000494:pharmacology; D008297:Male; D008803:Mianserin / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D011743:Pyrimidines / Q000494:pharmacology*; D012110:Reserpine / Q000494:pharmacology; D013997:Time Factors
D000596:Amino Acids; D000928:Antidepressive Agents; D001679:Biogenic Amines; D011743:Pyrimidines; D008803:Mianserin; D007520:Isocarboxazid; C054329:RS 2232; D012110:Reserpine; D007099:Imipramine