Potentiation effects of (+/-)huprine X, a new acetylcholinesterase inhibitor, on nicotinic receptors in rat cortical synaptosomes.

The present experiments were developed to analyze the direct and/or potentiation effect of (+/-)-12-amino-3-chloro-9-ethyl-6,7,10,11-tetrahydro-7,11-methanocycloocta[b]quinoline hydrochloride ((+/-)huprine X) on nicotinic receptors using a synaptosomal superfusion method. (+/-)Huprine X (1 microM, 10 microM) increased [(3)H]-ACh release only at 10 microM (46%; P < 0.001) in basal, but not in stimulated, conditions. This effect was completely reverted by mecamylamine (100 microM; MEC). Potentiation of evoked-[3H]-ACh release induced by ACh (1 microM) and by galantamine (GAL) 0.4 microM and physostigmine (PHY) 10 microM (55% and 50%, respectively; P < 0.001), two well-known allosteric compounds, corroborate that the present experimental approach is a suitable method to study potentiation effects on nicotinic receptors in the central nervous system nerve terminals. (+/-)Huprine X potentiated the evoked-[3H]-ACh release induced by ACh (1 microM) by 166% and 90% (P < 0.001) at 10 microM and 30 microM, respectively, and this effect was completely blocked by MEC (100 microM). In the presence of different ACh concentrations, (+/-)huprine X 10 microM potentiated evoked-[3H]-ACh release at low ACh concentrations, while a decrease in neurotransmitter release was observed at high ACh concentrations. The highest potentiation effect was obtained at the ACh/(+/-)huprine X concentration ratio of 1:10, and this potentiation was observed at as low a (+/-)huprine X concentration as 0.1 microM (P < 0.05). While the results suggest that huprine may enhance the potency or effectiveness of ACh by an effect involving nicotinic receptors we cannot completely discard that the results could be explained by acetylcholine esterase inhibition.