Abstract
Effect of MCI-225 on brain monoamine metabolism was examined in rats. MCI-225 (30 mg/kg, p.o.) had no influence on noradrenaline (NA) levels, but significantly inhibited the NA turnover in the hippocampus and hypothalamus. This compound also significantly increased the 5-hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine ratio in the cerebral cortex, hippocampus and striatum; and it enhanced the probenecid-induced 5-HIAA accumulation in the striatum. In the microdialysis study, MCI-225 markedly increased the NA output, but decreased the 3, 4-dihydroxyphenylethyleneglycol output from the hypothalamus of urethane-anesthetized rats. These results suggest that MCI-225 enhances both noradrenergic and serotonergic function by inhibiting NA uptake and accelerating 5-HT turnover, respectively.
