Dutar P, Bassant M H, Lamour Y
I.N.S.E.R.M., Unité 161, Paris, France.
Brain Res. 1990 Sep 10;527(1):32-40. doi: 10.1016/0006-8993(90)91057-n.
The effects of tetrahydro-9-aminoacridine (THA), an anticholinesterase drug, have been studied in the rat both in vivo (cerebral cortex) and in vitro (CA1 field of the hippocampus) and compared with those of physostigmine. In the cerebral cortex THA potentiated the excitatory effect of acetylcholine in most neurons, including cortical neurons recorded from chronic unanesthetized animals. In vitro, THA (but not physostigmine) had a depolarizing, atropine- and tetrodotoxin-insensitive effect. This effect is associated with an increase in membrane resistance which suggests a direct effect of THA on hippocampal neurons. In addition THA blocked the slow inhibitory postsynaptic potential. At the same concentration THA potentiated the slow cholinergic excitatory postsynaptic potential produced by electrical stimulation of the cholinergic afferents. Its potency was, however, about 10 times lower than that of physostigmine. These results show that THA: (1) is an anticholinesterase much less potent than physostigmine; but (2) has also direct effects on central neurons, not observed with physostigmine and unrelated to its anticholinesterase activity.
已在大鼠体内（大脑皮层）和体外（海马体CA1区）研究了抗胆碱酯酶药物四氢-9-氨基吖啶（THA）的作用，并与毒扁豆碱的作用进行了比较。在大脑皮层，THA增强了大多数神经元中乙酰胆碱的兴奋作用，包括从慢性未麻醉动物记录的皮层神经元。在体外，THA（但毒扁豆碱无此作用）具有去极化作用，且对阿托品和河豚毒素不敏感。这种作用与膜电阻增加有关，提示THA对海马神经元有直接作用。此外，THA阻断了缓慢的抑制性突触后电位。在相同浓度下，THA增强了电刺激胆碱能传入纤维产生的缓慢胆碱能兴奋性突触后电位。然而，其效力约比毒扁豆碱低10倍。这些结果表明：（1）THA是一种抗胆碱酯酶，其效力远低于毒扁豆碱；但（2）对中枢神经元也有直接作用，这是毒扁豆碱未观察到的，且与其抗胆碱酯酶活性无关。
