Reiner P B, McGeer E G
Department of Psychiatry, University of British Columbia, Vancouver, Canada.
Eur J Pharmacol. 1988 Oct 18;155(3):265-70. doi: 10.1016/0014-2999(88)90512-2.
Long-term administration of 9-amino-1,2,3,4-tetrahydroacridine (THA) has been reported to produce marked clinical improvement in patients suffering from Alzheimer's disease. The dramatic enhancement of cognitive function seen with THA contrasts sharply with the modest improvements seen with other forms of anticholinesterase therapy, suggesting that additional mechanisms might play a role in its therapeutic efficacy. When applied to hypothalamic histamine neurons maintained in vitro, THA produced a dose-dependent increase in action potential duration. By its effect upon action potential duration, THA may increase release of transmitter from the axon terminals of cortically projecting aminergic neurons which have been shown to degenerate in Alzheimer's disease. Thus, the therapeutic efficacy of THA may derive from a combination of its anticholinesterase activity and its effects upon the duration of action potentials of aminergic neurons.
据报道，长期服用9-氨基-1,2,3,4-四氢吖啶（THA）可使患有阿尔茨海默病的患者在临床上有显著改善。THA所带来的认知功能的显著增强与其他形式的抗胆碱酯酶疗法所带来的适度改善形成鲜明对比，这表明可能有其他机制在其治疗效果中发挥作用。当应用于体外培养的下丘脑组胺神经元时，THA使动作电位持续时间呈剂量依赖性增加。通过对动作电位持续时间的影响，THA可能增加来自皮质投射胺能神经元轴突终末的递质释放，而这些神经元在阿尔茨海默病中已被证明会退化。因此，THA的治疗效果可能源于其抗胆碱酯酶活性及其对胺能神经元动作电位持续时间的影响的共同作用。
