NIP-141, a multiple ion channel blocker, terminates aconitine-induced atrial fibrillation and prevents the rapid pacing-induced atrial effective refractory period shortening in dogs.
Hashimoto, Norio *; Yamashita, Toru; Fujikura, Naoki; Tsuruzoe, Nobutomo
[Miscellaneous Article] Europace. 9(4):246-251, April 2007.

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Aims: NIP-141 is a novel multiple ion channel blocker with atrial selective effects. In this study, we examined the effects of NIP-141 on aconitine-induced atrial fibrillation (AF) and rapid atrial pacing-induced atrial effective refractory period (ERP) shortening in dogs.

Methods and results: Aconitine AF was induced by the application of aconitine on the right appendage. NIP-141 (10 mg/kg) converted AF to sinus rhythm in 5 of 6 dogs. The Na channel blockers disopyramide (1 mg/kg) and phenytoin (10 mg/kg) also terminated AF, but the IKr blocker (d-sotalol; 4 mg/kg) and a Ca2 channel blocker (verapamil; 0.3 mg/kg) did not terminate AF in this model. To clarify the mechanism of AF termination, we examined the effects on ERP and conduction time, but NIP-141 (10 mg/kg) had no significant effects. In a short-term rapid atrial pacing model, NIP-141 (2.5 mg/kg/10 min, followed by 0.033 mg/kg/min) prevented atrial ERP shortening. We also found NIP-141 bound to Na channel site 2 receptor and L-type Ca2 channel, but not to Na channel site 1 receptor using radioligands binding assay.

Conclusion: NIP-141 terminated AF in aconitine-induced AF and prevented the atrial remodelling by short-term rapid pacing in dogs, possibly via the blocking of Na and Ca2 channels.

(C) Copyright Oxford University Press 2007.