M'Harzi M, Willig F, Gieules C, Palou A M, Oberlander C, Barzaghi F
Centre de Recherches Roussel UCLAF, Romainville, France.
Pharmacol Biochem Behav. 1997 Apr;56(4):663-8. doi: 10.1016/s0091-3057(96)00423-6.
The anti-amnesic effects of RU 47213 [1-(4-chlorophenoxycarbonyl)-1,2,5, 6-tetrahydropyridine-3-carboxaldehyde-O-methyloxime], a prodrug with oral and long-lasting cholinergic activity, were evaluated on working memory impairments, using tasks of unequal levels of difficulty involving the same reinforcement and motivation in rats: a spatial-based task in a radial maze and a delayed reinforced alternation task in a T-maze. Tetrahydroaminoacridine (THA; tacrine), a cholinesterase inhibitor was used as a reference. Groups of rats were trained in an automated radial maze or T-maze until they had attained an asymptotic level of performance. On test days, memory impairment was produced by administration of scopolamine (0.1 mg/kg s.c.) 15 min prior to testing. Both THA (1.3, and 5 mg/kg) and RU 47213 (0.2, 0.5, 1, and 2 mg/kg) given prior to testing markedly reduced or suppressed the scopolamine induced working memory deficits in both tasks. This activity was evidenced by either a significant decrease in the number of errors or an increase in the number of correct responses. These results show that RU 47213 possesses the capacity to reduce memory deficits induced by an impairment of cholinergic transmission in the rat.
RU 47213[1-(4-氯苯氧基羰基)-1,2,5,6-四氢吡啶-3-甲醛-O-甲基肟]是一种具有口服和长效胆碱能活性的前体药物，通过在大鼠中使用涉及相同强化和动机但难度不等的任务，即放射状迷宫中的空间任务和T迷宫中的延迟强化交替任务，来评估其对工作记忆损伤的抗遗忘作用。胆碱酯酶抑制剂四氢氨基吖啶（THA；他克林）用作对照。将大鼠分组在自动放射状迷宫或T迷宫中进行训练，直至达到稳定的表现水平。在测试日，在测试前15分钟皮下注射东莨菪碱（0.1mg/kg）造成记忆损伤。在测试前给予THA（1.3和5mg/kg）和RU 47213（0.2、0.5、1和2mg/kg）均显著减少或抑制了东莨菪碱在两项任务中诱导的工作记忆缺陷。错误数量的显著减少或正确反应数量的增加证明了这种活性。这些结果表明，RU 47213具有减少大鼠胆碱能传递受损引起的记忆缺陷的能力。
