title: Drug insight: If inhibitors as specific heart-rate-reducing agents.
abstract: Heart rate is determined primarily by spontaneously repeating net inward current carried by sodium ions and potassium ions through hyperpolarization-activated cyclic-nucleotide-gated channels. Within the heart, these channels are found most abundantly in sinoatrial cardiomyocytes. The channels open in response to membrane hyperpolarization, modulated by local cAMP concentrations. They permit activation of the I(f) current, which can be blocked specifically by molecules characterized by linked benzazepinone and benzocyclobutane rings, and which are devoid of effects on cardiac conduction, inotropy or peripheral vascular tone. The resulting heart-rate reduction has been effective in angina prevention in clinical trials involving 4,000 patients, using the prototype I(f) inhibitor, ivabradine. No serious adverse events have been attributed to the treatment; the most prominent side-effect is dose-related, always reversible and often transient visual symptoms that seldom result in voluntary drug discontinuation.
authors.affiliation: Division of Cardiovascular Pathophysiology, Howard Gilman Institute for Valvular Heart Diseases, Weill Medical College of Cornell University, New York-Presbyterian Hospital Weill Cornell Center, New York, NY 10021, USA. ero2002@med.cornell.edu
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Borer
mesh_terms: D000787:Angina Pectoris / Q000188:drug therapy*; D001552:Benzazepines / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004553:Electric Conductivity; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D015640:Ion Channel Gating; D007473:Ion Channels / Q000037:antagonists & inhibitors*; D000077550:Ivabradine; D009200:Myocardial Contraction / Q000187:drug effects; D012849:Sinoatrial Node / Q000187:drug effects*
chemical_list: D001552:Benzazepines; D002316:Cardiotonic Agents; D007473:Ion Channels; D000077550:Ivabradine