Mechanism of action of the new anti-ischemia drug ranolazine.
Myocardial ischemia is associated with reduced ATP fluxes and decreased energy supply resulting in disturbances of intracellular ion homeostasis in cardiac myocytes. In the recent years, increased persistent (late) sodium current was suggested to contribute to disturbed ion homeostasis by elevating intracellular sodium concentration with subsequent elevation of intracellular calcium. The new anti-ischemia drug ranolazine, a specific inhibitor of late sodium current, reduces sodium overload and hence ameliorates disturbed ion homeostasis. This is associated with symptomatic improvement of angina in patients. Moreover, ranolazine was shown to exhibit anti-arrhythmic effects. In the present article, we review the relevant pathophysiological concepts for the role of late sodium inhibition and summarize the most recent data from basic as well as clinical studies.
Dept. of Cardiology and Pneumology, Heart Center Göttingen, Robert-Koch-Strasse 40, 37075 Goettingen, Germany. hasenfus@med.uni-goettingen.de
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Maier
D000083:Acetanilides / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D000069458:Ranolazine; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects; D014882:Water-Electrolyte Balance / Q000187:drug effects
D000083:Acetanilides; D004791:Enzyme Inhibitors; D010879:Piperazines; D015222:Sodium Channels; D012964:Sodium; D000069458:Ranolazine; D002118:Calcium