NIK-247 Blocks Voltage-Dependent Ionic Currents in Crayfish Axon

Abstract

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 × 10^-4 M, in comparison with 3-AP and 4-AP which had IC₅₀'s of 3 × 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.