de Belleroche J, Gardiner I M
Department of Biochemistry, Charing Cross and Westminster Medical School, London.
Br J Pharmacol. 1988 Aug;94(4):1017-9. doi: 10.1111/j.1476-5381.1988.tb11615.x.
1,2,3,4-Tetrahydro-9-aminoacridine (THA) has an inhibitory effect on the activity of acetylcholinesterase which has led to its use in the treatment of Alzheimer's disease. Other actions of THA include the inhibition of voltage-dependent ion channels. In this paper we describe the effect of THA on the depolarization-induced release of [14C]-gamma-aminobutyric acid (GABA) from tissue slices of rat cerebral cortex. THA produced a dose-dependent inhibition of the 30 mM K+-evoked release of [14C]-GABA with an IC50 of 56 microM. The maximal response was an 84% inhibition of the evoked response. THA (up to a concentration of 1 mM) had no effect on the basal release of GABA. A similar inhibitory effect on the K+-evoked release of [14C]-GABA was seen with 4-aminopyridine (4-AP) but no inhibition was obtained with tetraethylammonium up to a concentration of 20 mM. The maximal inhibitory effect of 4-AP (39%) occurred at 1 mM (IC50 of 112 microM) and this response was much smaller in magnitude than that obtained with THA.
1,2,3,4-四氢-9-氨基吖啶（THA）对乙酰胆碱酯酶的活性具有抑制作用，这使其被用于治疗阿尔茨海默病。THA的其他作用包括抑制电压依赖性离子通道。在本文中，我们描述了THA对大鼠大脑皮质组织切片中去极化诱导的[14C] -γ-氨基丁酸（GABA）释放的影响。THA对30 mM K + 诱发的[14C] -GABA释放产生剂量依赖性抑制，IC50为56 μM。最大反应是对诱发反应的84%抑制。THA（浓度高达1 mM）对GABA的基础释放没有影响。4-氨基吡啶（4-AP）对K + 诱发的[14C] -GABA释放有类似的抑制作用，但浓度高达20 mM的四乙铵没有抑制作用。4-AP的最大抑制作用（39%）出现在1 mM（IC50为112 μM）时，且该反应的幅度远小于THA所产生的反应。
