Ishii Y, Sumi T
Department of Psychopharmacology, Psychiatric Research Institute of Tokyo, Japan.
Neuropharmacology. 1992 Jan;31(1):61-6. doi: 10.1016/0028-3908(92)90162-i.
Basal and high K(+)-stimulated efflux of endogenous ACh from slices of brain was measured to evaluate the cholinomimetic effect of 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b] quinoline monohydrate HCl (NIK-247) on the central nervous system. The drug NIK-247 dose-dependently accelerated the efflux of ACh from slices of striatum. The maximum increase produced by 1.0 x 10(-4) M of NIK-247 was 329% in basal and 1332% in 30 mM K(+)-stimulated efflux. This drug was nearly twice as potent as THA (9-amino-1,2,3,4-tetrahydroacridine HCl) but had the same potency as physostigmine, in enhancing basal efflux, although there was no significant difference between the efficacy of these drugs in enhancing the K(+)-stimulated efflux. Both basal and 50 mM K(+)-stimulated efflux of ACh were increased by NIK-247, not only from the striatum but also from slices of frontal cortex and hippocampus. The activity was more effective in the striatum than in other tissues, and more effective on K(+)-stimulated than on basal efflux, regardless of the region of the brain. These effects of NIK-247 may be a result mainly of its inhibition of cholinesterase and its other biological characteristics, such as K+ channel blockade, capable of modulating release of ACh, may not be of major importance.
通过测量脑片内源性乙酰胆碱（ACh）的基础释放量和高钾（K⁺）刺激后的释放量，来评估盐酸9-氨基-2,3,5,6,7,8-六氢-1H-环戊[b]喹啉一水合物（NIK-247）对中枢神经系统的拟胆碱作用。药物NIK-247剂量依赖性地加速了纹状体脑片中ACh的释放。1.0×10⁻⁴ M的NIK-247在基础释放量中产生的最大增加为329%，在30 mM K⁺刺激释放量中为1332%。在增强基础释放方面，该药物的效力几乎是THA（盐酸9-氨基-1,2,3,4-四氢吖啶）的两倍，但与毒扁豆碱的效力相同，尽管这些药物在增强K⁺刺激释放量方面的疗效没有显著差异。NIK-247不仅增加了纹状体脑片中ACh的基础释放量和50 mM K⁺刺激释放量，还增加了额叶皮质和海马体脑片中ACh的释放量。无论脑区如何，该活性在纹状体中比在其他组织中更有效，对K⁺刺激释放的作用比对基础释放更有效。NIK-247的这些作用可能主要是其抑制胆碱酯酶的结果，而其其他生物学特性，如钾离子通道阻滞，虽然能够调节ACh的释放，但可能并不重要。
