Suzuki T, Nonaka H, Fujimoto K, Kawashima K
Department of Pharmacology, Kyoritsu College of Pharmacy, Tokyo, Japan.
Jpn J Pharmacol. 1994 Aug;65(4):337-42. doi: 10.1254/jjp.65.337.
We examined the effects of tacrine (9-amino-1,2,3,4-tetrahydroacridine) on endogenous acetylcholine (ACh) release from rat hippocampal slices. Tacrine (more than 1 microM) increased the measurable amount of basal ACh release. On the other hand, in the presence of physostigmine (50 microM; under this condition, cholinesterase activity was inhibited), tacrine did not enhance the basal ACh release. Tacrine at more than 100 microM increased the submaximal electrical stimulation-evoked release of ACh in both the absence and presence of physostigmine (50 microM). This effect of tacrine was abolished by a combination of atropine (100 mM) and physostigmine. These results indicate that a high-dose of tacrine increases cholinergic neurotransmission not only by inhibition of cholinesterase but also by increasing ACh release through an atropine-like effect, perhaps by blockade of part of the process of muscarinic autoinhibition.
我们研究了他克林（9-氨基-1,2,3,4-四氢吖啶）对大鼠海马切片内源性乙酰胆碱（ACh）释放的影响。他克林（浓度超过1微摩尔）增加了可测量的基础ACh释放量。另一方面，在毒扁豆碱（50微摩尔；在此条件下，胆碱酯酶活性受到抑制）存在的情况下，他克林并未增强基础ACh释放。浓度超过100微摩尔的他克林在毒扁豆碱（50微摩尔）不存在和存在的情况下均增加了次最大电刺激诱发的ACh释放。他克林的这种作用被阿托品（100毫摩尔）和毒扁豆碱的联合使用所消除。这些结果表明，高剂量的他克林不仅通过抑制胆碱酯酶增加胆碱能神经传递，还通过类似阿托品的作用增加ACh释放，可能是通过阻断部分毒蕈碱自身抑制过程来实现的。
