NIK-247 blocks voltage-dependent ionic currents in crayfish axon.
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.
Kojima
J
J
Division of Pharmacology, Omiya Research Laboratory, Nikken Chemicals Co., Ltd., Japan.
Sugawara
Y
Y
Obara
S
S
D015761:4-Aminopyridine / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D003400:Astacoidea; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004594:Electrophysiology; D007473:Ion Channels / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000502:physiology; D011619:Psychotropic Drugs / Q000494:pharmacology*; D013619:Tacrine / Q000494:pharmacology
D000634:Aminoquinolines; D002800:Cholinesterase Inhibitors; D007473:Ion Channels; D011619:Psychotropic Drugs; D013619:Tacrine; D015761:4-Aminopyridine; C049860:amiridine; D011188:Potassium