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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.
Europace. 2007 Apr; 9(4):246-51.E

Abstract

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 I(Kr) blocker (d-sotalol; 4 mg/kg) and a Ca(2+) 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 Ca(2+) 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 Ca(2+) channels.

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Authors+Show Affiliations

Hashimoto N
Biological Research Laboratories, Nissan Chemical Industries Ltd, 1470 Shiraoka, Minamisaitama, Saitama 349-0294, Japan. hashimotot@nissanchem.co.jp
Yamashita T
No affiliation info available
Fujikura N
No affiliation info available
Tsuruzoe N
No affiliation info available

MeSH

AnimalsAtrial FibrillationBenzopyransCardiac Pacing, ArtificialDogsDose-Response Relationship, DrugHeart Conduction SystemIon ChannelsRefractory Period, ElectrophysiologicalTreatment Outcome

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17350982

Citation

Hashimoto, Norio, et al. "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." Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups On Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology, vol. 9, no. 4, 2007, pp. 246-51.
Hashimoto N, Yamashita T, Fujikura N, et al. 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. Europace. 2007;9(4):246-51.
Hashimoto, N., Yamashita, T., Fujikura, N., & Tsuruzoe, N. (2007). 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. Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups On Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology, 9(4), 246-51.
Hashimoto N, et al. 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. Europace. 2007;9(4):246-51. PubMed PMID: 17350982.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Hashimoto,Norio, AU - Yamashita,Toru, AU - Fujikura,Naoki, AU - Tsuruzoe,Nobutomo, Y1 - 2007/03/09/ PY - 2007/3/14/pubmed PY - 2007/6/20/medline PY - 2007/3/14/entrez SP - 246 EP - 51 JF - Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology JO - Europace VL - 9 IS - 4 N2 - 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 I(Kr) blocker (d-sotalol; 4 mg/kg) and a Ca(2+) 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 Ca(2+) 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 Ca(2+) channels. SN - 1099-5129 UR - https://www.unboundmedicine.com/medline/citation/17350982/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_ L2 - https://academic.oup.com/europace/article-lookup/doi/10.1093/europace/eum018 DB - PRIME DP - Unbound Medicine ER -