title: [Na+/H+ exchange inhibitors for ischemic diseases].
abstract: Cariporide, HOE642 (4-isopropyl-3-methylsulphonylbenzoyl-guanidine methanesulphonate), a novel Na(+)-H+ exchange (NHE) subtype 1 inhibitor, has cardioprotective effects including an antifibrillatory effect on the coronary ischemia/reperfusion induced arrhythmias not only in in vitro, but also in vivo animal hearts, which might be induced by intracellular Ca2+ overload following myocardial ischemia. This antifibrillatory effects on reperfusion arrhythmias were observed even when the drug was administered after induction of coronary ischemia or even when the drug was administered simultaneously with reperfusion. Other NHE inhibitors also have similar antiarrhythmic and antifibrillatory effects as cariporide and these drugs had almost no deleterious effects on the heart rate and blood pressure, nor ECG parameters. The antifibrillatory mechanism of NHE inhibitors may be due to their NHE inhibition as judged by the doses used, and they may become useful for treating or preventing arrhythmias in patients with coronary artery diseases.
authors.affiliation: Department of Pharmacology, Yamanashi Medical University, Yamanashi 409-3898, Japan. keitaroh@res.yamanashi-med.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents; D001145:Arrhythmias, Cardiac / Q000188:drug therapy; D002118:Calcium / Q000378:metabolism; D027682:Cation Transport Proteins; D002986:Clinical Trials as Topic; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D017202:Myocardial Ischemia / Q000188:drug therapy*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000502:physiology; D013450:Sulfones / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000889:Anti-Arrhythmia Agents; D027682:Cation Transport Proteins; D006146:Guanidines; D008565:Membrane Proteins; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide; D002118:Calcium