[Selection and pharmacological characterisation of Procoralan, a selective inhibitor of the pacemaker If current].
The screening of a series of benzocycloalkane derivatives led to the selection of Procoralan (ivabradine), the first selective inhibitor of the depolarizing If (funny) current of the sinus node, for the treament of myocardial ischaemia. In vitro, this compound reduces the spontaneous beating rate of isolated right rat atria and the firing rate of the action potential of rabbit sinus node preparations. This effect is explained by a reduction in the diastolic depolarisation slope of the action potential and underlies a selective inhibition of the pacemaker If current. In vivo, it induces a selective reduction in heart rate both at rest and during exercise. It preserves myocardial contractility, atrioventricular conduction and ventricular repolarisation duration. Ivabradine exerts a similar anti-ischaemic activity in exercise-induced myocardial ischaemia in pigs to that of a beta-blocker and, furthermore, it limits to a greater extent ischaemic myocardial contractile dysfunction.
Vilaine
Jean-Paul
JP
Institut de Recherches Servier, Division Pathologies Cardiaques et Vasculaires, Suresnes, France. jean-paul.vilaine@fr.netgrs.com
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology* / Q000627:therapeutic use; D001683:Biological Clocks / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D000077550:Ivabradine; D011817:Rabbits; D051381:Rats; D012849:Sinoatrial Node / Q000187:drug effects; D013552:Swine
D001552:Benzazepines; D002316:Cardiotonic Agents; D000077550:Ivabradine