La découverte de l’ivabradine (Procoralan®), inhibiteur sélectif du courantpacemakerIf: Une nouvelle approche thérapeutique des cardiopathies ischémiques

Vilaine, Jean‐Paul

doi:10.1051/medsci/200622187

Cited by 2 publications

(1 citation statement)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several molecules were developed to block the pacemaker channels, such as alinidine, cilobradine, zatebradina, ivabradine and ZD7288, but only ivabradine (a benzocyclobutane compound) has passed all the clinical trials and is currently marketed as an anti-anginal drug in different states, under the trade name of Procoralan [20,21,22,23]. Ivabradine represents the most specific and selective inhibitor for the pacemaker channels.…”

Section: Introductionmentioning

confidence: 99%

The Biological Effects of Ivabradine in Cardiovascular Disease

Speranza

Franceschelli

Riccioni³

2012

Molecules

View full text Add to dashboard Cite

A large number of studies in healthy and asymptomatic subjects, as well as patients with already established cardiovascular disease (CAD) have demonstrated that heart rate (HR) is a very important and major independent cardiovascular risk factor for prognosis. Lowering heart rate reduces cardiac work, thereby diminishing myocardial oxygen demand. Several experimental studies in animals, including dogs and pigs, have clarified the beneficial effects of ivabradine associated with HR lowering. Ivabradine is a selective inhibitor of the hyperpolarisation activated cyclic-nucleotide-gated funny current (If) involved in pacemaker generation and responsiveness of the sino-atrial node (SAN), which result in HR reduction with no other apparent direct cardiovascular effects. Several studies show that ivabradine substantially and significantly reduces major risks associated with heart failure when added to guideline-based and evidence-based treatment. However the biological effect of ivabradine have yet to be studied. This effects can appear directly on myocardium or on a systemic level improving endothelial function and modulating immune cell migration. Indeed ivabradine is an 'open-channel' blocker of human hyperpolarization-activated cyclic nucleotide gated channels of type-4 (hHCN4), and a 'closed-channel' blocker of mouse HCN1 channels in a dose-dependent manner. At endothelial level ivabradine decreased monocyte chemotactin protein-1 mRNA expression and exerted a potent anti-oxidative effect through reduction of vascular NADPH oxidase activity. Finally, on an immune level, ivabradine inhibits the chemokine-induced migration of CD4-positive lymphocytes. In this review, we discuss the biological effects of ivabradine and highlight its effects on CAD.

show abstract