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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<jats:sub>50<\/jats:sub>: 342 and 529 nM, respectively). In canine ventricular myocytes, SZV-2649 (10 \u00b5M) decreased the densities of I<jats:sub>Kr<\/jats:sub>, and I<jats:sub>to<\/jats:sub> outward and I<jats:sub>NaL<\/jats:sub> and I<jats:sub>CaL<\/jats:sub> inward currents. The compound (2.5\u201310 \u00b5M) elicited Class IB type V<jats:sub>max<\/jats:sub> reducing and Class III type action potential duration prolonging effects in dog right ventricular muscle preparations. In canine atrial muscle, SZV-2629 (2.5\u201310 \u00b5M) moderately prolonged action potential duration and this effect was greatly augmented in preparations pretreated with 1 \u00b5M 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.<\/jats:p>","DOI":"10.1038\/s41598-024-73576-5","type":"journal-article","created":{"date-parts":[[2024,10,5]],"date-time":"2024-10-05T08:01:54Z","timestamp":1728115314000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of SZV-2649, a new multiple ion channel inhibitor mexiletine analogue"],"prefix":"10.1038","volume":"14","author":[{"given":"Aiman Saleh A.","family":"Mohammed","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Naveed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara","family":"Szabados","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Istv\u00e1n","family":"Szatm\u00e1ri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e1lint","family":"L\u0151rinczi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P\u00e9ter","family":"M\u00e1tyus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Czompa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P\u00e9ter","family":"Orvos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zolt\u00e1n","family":"Husti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tibor","family":"Hornyik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leila","family":"Topal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Szilvia","family":"D\u00e9ri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norbert","family":"Jost","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L\u00e1szl\u00f3","family":"Vir\u00e1g","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P\u00e9ter","family":"Bencsik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Istv\u00e1n","family":"Baczk\u00f3","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e1s","family":"Varr\u00f3","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,10,5]]},"reference":[{"issue":"8","key":"73576_CR1","doi-asserted-by":"publisher","first-page":"e153","DOI":"10.1161\/CIR.0000000000001052","volume":"145","author":"CW Tsao","year":"2022","unstructured":"Tsao, C. 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