Effects of AE0047, a novel Ca antagonist, on monoamine, acetylcholine and neuroactive amino acids contents in rat brain

Abstract

Effects of AE0047, a novel calcium antagonist, on monoamine, acetylcholine (ACh) and neuroactive amino acid contents in rat brain were examined. Cerebral ACh content was elevated by the administration of AE0047 (100 mg/kg, p.o.). Striatal norepinephrine and dopamine contents were decreased and increased, respectively, following the administration of 10 mg/kg and 100 mg/kg of AE0047. The administration of AE0047 (10, 30 and 100 mg/kg, p.o.) invariably induced increases in 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid contents in the cerebral cortex. Although AE0047 (100 mg/kg, p.o.) had no effect on the tryptophan hydroxylase activity in the cerebral cortex, striatum and hippocampus, in vitro addition of 10^-8-10^-6M AE0047 induced a significant increase of [¹⁴C]5-HT uptake into cerebral cortical slices. AE0047 administration (30 and 100 mg/kg, p.o.) also induced a significant decrease of cortical taurine content. These results suggest that AE0047 may be a drug that stimulates 5-HT turnover via the accentuation of 5-HT uptake.