Effects of SZV-2649, a new multiple ion channel inhibitor mexiletine analogue

The antiarrhythmic and cardiac electrophysiological effects of SZV-2649 that contains a 2,6-diiodophenoxy moiety but lacks the benzofuran ring system present in amiodarone, were studied in mammalian cell line, rat and dog cardiac preparations. SZV-2649 exerted antiarrhythmic effects against coronary...

Teljes leírás

Elmentve itt :
Bibliográfiai részletek
Szerzők: Mohammed Aiman
Naveed Muhammad
Szabados Tamara
Szatmári István
Lőrinczi Bálint
Mátyus Péter
Czompa Andrea
Orvos Péter
Husti Zoltán
Hornyik Tibor
Topal Leila
Déri Szilvia
Jost Norbert László
Virág László
Bencsik Péter
Baczkó István
Varró András
Dokumentumtípus: Cikk
Megjelent: 2024
Sorozat:SCIENTIFIC REPORTS 14 No. 1
Tárgyszavak:
doi:10.1038/s41598-024-73576-5

mtmt:35438124
Online Access:http://publicatio.bibl.u-szeged.hu/34843
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520 3 |a The antiarrhythmic and cardiac electrophysiological effects of SZV-2649 that contains a 2,6-diiodophenoxy moiety but lacks the benzofuran ring system present in amiodarone, were studied in mammalian cell line, rat and dog cardiac preparations. SZV-2649 exerted antiarrhythmic effects against coronary artery occlusion/reperfusion induced ventricular arrhythmias in rats and in acetylcholine- and burst stimulation induced atrial fibrillation in dogs. SZV-2649 inhibited hERG and GIRK currents in HEK cells (IC 50 : 342 and 529 nM, respectively). In canine ventricular myocytes, SZV-2649 (10 µM) decreased the densities of I Kr , and I to outward and I NaL and I CaL inward currents. The compound (2.5–10 µM) elicited Class IB type V max reducing and Class III type action potential duration prolonging effects in dog right ventricular muscle preparations. In canine atrial muscle, SZV-2629 (2.5–10 µM) moderately prolonged action potential duration and this effect was greatly augmented in preparations pretreated with 1 µM carbachol. In conclusion, SZV-2649, has antiarrhythmic effects based on its multiple ion channel blocking properties. Since its chemical structure substantially differs from that of amiodarone, it is expected that SZV-2649 would exhibit fewer adverse effects than the currently used most effective multichannel inhibitor drug amiodarone and may be a promising molecule for further development. 
650 4 |a Általános orvostudomány 
650 4 |a Klinikai orvostan 
700 0 1 |a Naveed Muhammad  |e aut 
700 0 1 |a Szabados Tamara  |e aut 
700 0 1 |a Szatmári István  |e aut 
700 0 1 |a Lőrinczi Bálint  |e aut 
700 0 1 |a Mátyus Péter  |e aut 
700 0 1 |a Czompa Andrea  |e aut 
700 0 1 |a Orvos Péter  |e aut 
700 0 1 |a Husti Zoltán  |e aut 
700 0 1 |a Hornyik Tibor  |e aut 
700 0 1 |a Topal Leila  |e aut 
700 0 1 |a Déri Szilvia  |e aut 
700 0 1 |a Jost Norbert László  |e aut 
700 0 1 |a Virág László  |e aut 
700 0 1 |a Bencsik Péter  |e aut 
700 0 1 |a Baczkó István  |e aut 
700 0 1 |a Varró András  |e aut 
856 4 0 |u http://publicatio.bibl.u-szeged.hu/34843/1/SciRep_23188_Mohammed_2024.pdf  |z Dokumentum-elérés