Bejar C, Wang R H, Weinstock M
Department of Pharmacology, Hebrew University, Hadassah Medical Centre, Ein Kerem, Jerusalem, Israel.
Eur J Pharmacol. 1999 Nov 3;383(3):231-40. doi: 10.1016/s0014-2999(99)00643-3.
The effect of rivastigmine on memory impairments induced in rats by scopolamine (0.5 mg/kg) was assessed in the Morris water maze and passive avoidance tests and compared with that of tacrine (2.5-17.7 mg/kg). Rivastigmine, (0.5-2.5 mg/kg) inhibited cholinesterase in the cortex and hippocampus by 21-60% and antagonised the deficits in working and reference memory. Tacrine (12.5 and 17.7 mg/kg) produced significantly less inhibition of cholinesterase in the hippocampus but more in the striatum than rivastigmine (0.75 and 1.5 mg/kg) and only antagonised the deficit in reference memory. Rivastigmine (1.5 and 2.5 mg/kg) or tacrine (12.5 mg/kg), injected immediately after completion of the acquisition trial in the passive avoidance test, antagonised the deficit induced by scopolamine (1 mg/kg) in memory retention. The inability of higher doses of the cholinesterase inhibitors to antagonise memory deficits induced by scopolamine may be related to excessive cholinergic stimulation in the central nervous system.
在莫里斯水迷宫和被动回避试验中评估了卡巴拉汀对东莨菪碱(0.5毫克/千克)诱导的大鼠记忆损伤的影响,并与他克林(2.5 - 17.7毫克/千克)进行了比较。卡巴拉汀(0.5 - 2.5毫克/千克)使皮质和海马中的胆碱酯酶抑制21 - 60%,并拮抗工作记忆和参考记忆缺陷。他克林(12.5和17.7毫克/千克)在海马中对胆碱酯酶的抑制作用明显小于卡巴拉汀(0.75和1.5毫克/千克),但在纹状体中的抑制作用更大,且仅拮抗参考记忆缺陷。在被动回避试验中完成获得性试验后立即注射卡巴拉汀(1.5和2.5毫克/千克)或他克林(12.5毫克/千克),可拮抗东莨菪碱(1毫克/千克)诱导的记忆保持缺陷。高剂量胆碱酯酶抑制剂无法拮抗东莨菪碱诱导的记忆缺陷可能与中枢神经系统中胆碱能过度刺激有关。