Pharmacological studies on Y-8894 (VI). The effect on monoamine uptake and turnover in mouse brain

The effect of Y-8894 (+/-) 2-[[o-(2-thenyl)phenoxy]methyl] morpholine maleate, which has been shown to improve experimentally induced learning and memory deficits, on cerebral monoamine uptake and turnover was studied in the mouse. The following results were obtained: 1) It inhibited in vitro norepinephrine (NE) uptake to the mouse cerebral synaptosomal fractions about 800 and 1250 times more potently than it did those of dopamine (DA) and serotonin (5-HT), respectively. 2) It dose-dependently inhibited in vivo NE uptake, but not DA or 5-HT uptake. 3) It reduced the accumulation of the NE metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), increased that of the 5-HT metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and had no effect on that of the DA metabolite, homovanillic acid (HVA). These effects were compared with those of imipramine, calcium hopantenate (Ca-hopantenate) and dihydroergotoxine. Y-8894 appeared to act by stimulating the noradrenergic receptor, and it acts to a lesser extent by blocking the serotonergic receptor in the brain.