Kojima J, Sugawara Y, Obara S
Division of Pharmacology, Omiya Research Laboratory, Nikken Chemicals Co., Ltd., Japan.
Jpn J Pharmacol. 1991 Dec;57(4):545-52. doi: 10.1254/jjp.57.545.
NIK-247 (9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]-quinoline hydrochloride hydrate), an acetylcholinesterase inhibitor, is structurally related to 4-aminopyridine (AP). Its effects on ionic currents were examined in the artificial node of the crayfish axon under voltage-clamp. When applied externally, NIK-247 reversibly suppressed both inward and outward currents. Effects on K currents were further studied in the presence of tetrodotoxin. NIK-247 suppressed the K current dose-dependently, but with an IC50 at of 10(-3) M. THA (9-amino-1,2,3,4-tetra-hydroacridine hydrochloride hydrate), a related inhibitor, similarly suppressed the K current with an IC50 of 5 x 10(-4) M, in comparison with 3-AP and 4-AP which had IC50's of 3 x 10(-5) M and at 10(-5) M, respectively. Furthermore, NIK-247 (and THA) suppressed the K current uniformly for the whole time course, whereas AP the AP's suppressed mainly the fast activating and inactivating K current with a voltage- and frequency-dependent recovery. Therefore, NIK-247 and THA seem to be neither potent nor very specific as ionic channel blockers. With respect to the K current, however, they clearly differ from the AP's in their mode of suppression.
NIK-247（9-氨基-2,3,5,6,7,8-六氢-1H-环戊并[b]喹啉盐酸盐水合物）是一种乙酰胆碱酯酶抑制剂，在结构上与4-氨基吡啶（AP）相关。在电压钳制下，研究了其对小龙虾轴突人工节点离子电流的影响。当外部施加时，NIK-247可逆地抑制内向和外向电流。在存在河豚毒素的情况下，进一步研究了其对钾电流的影响。NIK-247剂量依赖性地抑制钾电流，但其半数抑制浓度（IC50）为10^(-3) M。相关抑制剂THA（9-氨基-1,2,3,4-四氢吖啶盐酸盐水合物）同样抑制钾电流，其IC50为5×10^(-4) M，相比之下，3-AP和4-AP的IC50分别为3×10^(-5) M和10^(-5) M。此外，NIK-247（和THA）在整个时间过程中均一性地抑制钾电流，而AP主要抑制快速激活和失活的钾电流，并具有电压和频率依赖性恢复。因此，NIK-247和THA作为离子通道阻滞剂似乎既不强效也不具有很高的特异性。然而，就钾电流而言，它们在抑制模式上明显不同于AP。
