Ivabradine: pharmacodynamic aspects of its clinical use.
Ivabradine has been approved as a heart rate-lowering agent for use in the treatment of chronic stable angina pectoris in case of contraindication or intolerance to beta-blockers. This drug effectively lowers the heart rate by inhibiting the pacemaker current I(f) in the sinoatrial node. It appears to induce fewer adverse reactions than other drugs used for reducing the heart rate, such as calcium channel blockers or beta-blockers. Because of this favorable profile, ivabradine could become the first-choice drug when pure heart rate-lowering is the therapeutic goal. This review evaluates experimental and preclinical data to investigate the possibilities, as well as the limitations, of the clinical use of ivabradine. In experimental studies, it has been shown that ivabradine does have some unfavorable pharmacodynamic properties, such as the block of all four hyperpolarization-activated cyclic nucleotide-gated channels and block of other ion channels at high concentrations. Clinical studies, however, indicate that those properties do not result in clinical consequences as long as ivabradine is given at the recommended dose and contraindications are strictly observed.
Stieber
Juliane
J
Institute for Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany. stieber@pharmakologie.uni-erlangen.de
D000787:Angina Pectoris / Q000188:drug therapy / Q000503:physiopathology; D000818:Animals; D001552:Benzazepines / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D002908:Chronic Disease; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000037:antagonists & inhibitors; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007473:Ion Channels / Q000037:antagonists & inhibitors; D000077550:Ivabradine
D001552:Benzazepines; D054815:Cyclic Nucleotide-Gated Cation Channels; D007473:Ion Channels; D000077550:Ivabradine