title: Drugs preventing Na+ and Ca2+ overload.
abstract: Cardiac intracellular Na+and Ca2+homeostasis is regulated by the concerted action of ion channels, pumps and exchangers. The Na+, K+-ATPase produces the electrochemical concentration gradient for Na+, which is the driving force for Ca2+removal from the cytosol via the Na+/Ca2+exchange. Reduction of this gradient by increased intracellular Na+concentration leads to cellular Ca2+overload resulting in arrhythmias and contractile dysfunction. Na+and Ca2+overload-associated arrhythmias can be produced experimentally by inhibition of Na+efflux (digitalis-induced intoxication) and by abnormal Na+influx via modulated Na+channels (veratridine, DPI 201-106; hypoxia) or via the Na+, H+exchanger. Theoretically, blockers of Na+and Ca2+channels, inhibitors of abnormal oscillatory release of Ca2+from internal stores or modulators of the Na+, Ca2+and Na+, H+exchanger activities could protect against cellular Na+and Ca2+overload. Three exemplary drugs that prevent Na+and Ca2+overload, i.e. the benzothiazolamine R56865, the methylenephenoxydioxy-derivative CP-060S, and the benzoyl-guanidine Hoe 642, a Na+, H+exchange blocker, are briefly reviewed with respect to their efficacy on digitalis-, veratridine- and ischaemia/reperfusion-induced arrhythmias.
authors: Institut für Pharmakologie und Toxikologie, Universitätsklinikum Carl Gustav Carus, TU Dresden, Karl-Marx-Strasse 3, Dresden, D-01109, Germany.
authors: U
authors: U
authors: Ravens
authors: H M
authors: HM
authors: Himmel
mesh_terms: D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy; D052160:Benzothiazoles; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D010880:Piperidines / Q000494:pharmacology*; D012964:Sodium / Q000502:physiology; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000502:physiology; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000502:physiology; D013450:Sulfones / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines
chemical_list: D000889:Anti-Arrhythmia Agents; D052160:Benzothiazoles; C104781:CP 060S; D002121:Calcium Channel Blockers; D006146:Guanidines; D010880:Piperidines; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; D013844:Thiazoles; D053778:Thiazolidines; C074107:3-methylsulfonyl-4-piperidinobenzoyl guanidine; C054551:R 56865; D012964:Sodium; D002118:Calcium