Evaluation of a cholinomimetic drug, 9-amino-2,3,5,6,7,8-hexahydro-1h-cyclopenta [b] quinoline (NIK-247), as an enhancer of endogenous efflux of acetylcholine from brain slices

Abstract

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 HC1 (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 × 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-l,2,3,4-tetrahydroacridine HC1) 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.