Cheng D H, Tang X C
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences.
Pharmacol Biochem Behav. 1998 Jun;60(2):377-86. doi: 10.1016/s0091-3057(97)00601-1.
Comparative effects of cholinesterase inhibitors (ChEI) huperzine A with E2020 and tacrine on the radial maze performance in ethylcholine mustard aziridinium ion (AF64A)-treated rat and inhibition of cholinesterase activity were studied. The intracerebroventricular (i.c.v.) injection of AF64A (3 nmol/side) caused significant impairment in the rat's ability to fulfill the partially baited maze paradigm. Oral huperzine A (0.5-0.8 mg/kg), E2020 (1.0-2.0 mg/kg), and tacrine (8.0 mg/kg) effectively reversed AF64A-induced working memory deficit. The doses that improved AF64A-induced memory deficit were correlated to about 25-30% (huperzine A) and less than 10% (E2020, tacrine) inhibition of acetylcholinesterase (AChE) activity in the cortex and hippocampus. Huperzine A, E2020 and tacrine all produced dose-dependent inhibition of brain AChE following i.c.v. and oral administration. Oral huperzine A exhibited higher efficacy on the inhibition of AChE in the cortex and hippocampus than those of E2020 and tacrine. Tacrine was more effective in inhibiting plasma butyrylcholinesterase (BuChE) than it was brain AChE. Conversely, the BuChE activity was less affected by huperzine A and E2020. The results showed that huperzine A had high bioavailability and more selective inhibition on AChE activity in cortex and hippocampus. Huperzine A fits more closely with the established criteria for an ideal AChE inhibitor to be used in clinical studies.
研究了胆碱酯酶抑制剂石杉碱甲与E2020和他克林对乙基胆碱氮芥啶离子（AF64A）处理的大鼠放射状迷宫行为表现的比较作用以及对胆碱酯酶活性的抑制作用。脑室内（i.c.v.）注射AF64A（3 nmol/侧）导致大鼠完成部分诱饵迷宫范式的能力显著受损。口服石杉碱甲（0.5 - 0.8 mg/kg）、E2020（1.0 - 2.0 mg/kg）和他克林（8.0 mg/kg）可有效逆转AF64A诱导的工作记忆缺陷。改善AF64A诱导的记忆缺陷的剂量与皮质和海马中乙酰胆碱酯酶（AChE）活性受到约25 - 30%（石杉碱甲）和不到10%（E2020、他克林）的抑制相关。石杉碱甲、E2020和他克林经脑室内和口服给药后均产生剂量依赖性的脑AChE抑制作用。口服石杉碱甲对皮质和海马中AChE的抑制作用比E2020和他克林更高。他克林对血浆丁酰胆碱酯酶（BuChE）的抑制作用比对脑AChE更有效。相反，石杉碱甲和E2020对BuChE活性的影响较小。结果表明，石杉碱甲具有高生物利用度，对皮质和海马中的AChE活性具有更具选择性的抑制作用。石杉碱甲更符合用于临床研究的理想AChE抑制剂的既定标准。
