Wang R H, Bejar C, Weinstock M
Department of Pharmacology, Hebrew University, Hadassah Medical Centre, Jerusalem, Israel.
Neuropharmacology. 2000 Jan 28;39(3):497-506. doi: 10.1016/s0028-3908(99)00157-4.
This study compared the effect of rivastigmine on cholinesterase (ChE) activity in different brain regions, heart, skeletal muscle and plasma and on the cognitive impairment induced by scopolamine (0.5 mg/kg) in male and female rats. Rats were injected s.c. with saline or rivastigmine (0.75-2.5 mg/kg) or physostigmine (0.05 mg/kg) and killed 30-120 min later. Amelioration of scopolamine-induced memory deficits by rivastigmine (0.75 mg/kg) was assessed in the Morris water maze. There were no gender differences in spatial memory or basal ChE activity in the brain or other organs. Rivastigmine (0.75 and 1.5 mg/kg) and physostigmine (0.05 mg/kg) caused significantly greater ChE inhibition in females than in males (P<0.01) in the cerebral cortex, hippocampus and striatum, but not in the periphery 30 and 60 min after injection. Rivastigmine was also more effective in antagonising the scopolamine-induced spatial memory impairment in female than in male rats. Ovariectomy did not affect the degree of enzyme inhibition by rivastigmine in any brain area. Orchidectomy completely abolished the difference in enzyme inhibition. It is concluded that a testicular hormone suppresses the effect of rivastigmine, by reducing the amount of drug reaching the brain or its interaction with ChE.
本研究比较了卡巴拉汀对雄性和雌性大鼠不同脑区、心脏、骨骼肌及血浆中胆碱酯酶（ChE）活性的影响，以及对东莨菪碱（0.5mg/kg）诱导的认知障碍的影响。大鼠皮下注射生理盐水、卡巴拉汀（0.75 - 2.5mg/kg）或毒扁豆碱（0.05mg/kg），30 - 120分钟后处死。在莫里斯水迷宫中评估卡巴拉汀（0.75mg/kg）对东莨菪碱诱导的记忆缺陷的改善作用。在空间记忆、脑或其他器官的基础ChE活性方面不存在性别差异。注射后30分钟和60分钟时，卡巴拉汀（0.75和1.5mg/kg）及毒扁豆碱（0.05mg/kg）在雌性大鼠大脑皮层、海马体和纹状体中引起的ChE抑制作用显著大于雄性大鼠（P<0.01），但在外周组织中无此差异。卡巴拉汀在拮抗东莨菪碱诱导的雌性大鼠空间记忆损伤方面也比雄性大鼠更有效。卵巢切除不影响卡巴拉汀在任何脑区的酶抑制程度。睾丸切除则完全消除了酶抑制的差异。结论是，睾丸激素通过减少到达大脑的药物量或其与ChE的相互作用来抑制卡巴拉汀的作用。
