EFFECT OF THE NOVEL HIGH-AFFINITY CHOLINE UPTAKE ENHANCER ,7,8-TETRAHYDROFURO[2,3-B]QUINOLIN-4-YL)ACETOAMIDE ON DEFICITS OF WATER MAZE-LEARNING IN RATS

The pharmacological properties of MKC-231 -yl)-N-(2,3-dimethyl-5,6,7,8 -tetrahydrofuro[2,3-b] quinolin-4-yl)acetoamide, CAS 135463-81-9) in c omparison with an acetylcholinesterase (AChE) inhibitor, tacrine (CAS 1684-40-8) were studied. MKC-231(10(-10)-10(-6) mol/l) significantly i ncreased high affinity choline uptake (HACU) when it was incubated wit h the hippocampal synaptosomes of ethylcholine mustard aziridinium ion (AF64A) treated rats, but not of normal rats. MKC-231 did not affect the AChE activity, [H-3]- quinuclidinyl benzilate binding, and [H-3]-p irenzepine binding. Oral administration of MKC-231 (1-10 mg/kg) signif icantly improved the learning deficits in the Morris' water maze of AF 64A-treated rats, but it did not produce any significant side effects, like tremor, salivation or hypothermia, which were observed in rats t reated with high doses of tacrine. Tacrine (0.1-3 mg/kg p.o.) failed t o ameliorate the learning deficits in AF64A-treated rats. These result s suggest that MKC-231 is a novel and quite unique compound, which imp roves the memory impairment induced by AF64A through the enhancement o f HACU without any side effects at the effective doses.