Heart contractility antiarrhythmic agents

Mechanism of Action An antianginal, antihypertensive, and antiarrhythmic agent that inhibits calcium movement across cardiac and vascular smooth-muscle cell membranes. This action causes the dilation of coronary arteries, peripheral arteries, and arterioles. Therapeutic Effect Decreases heart rate and myocardial contractility, slows SA and AV conduction, and decreases total peripheral vascular resistance by vasodilation. 

The antiarrhythmic agent rythmol (78a) and its silicon analogue sila-rythmol (78b for the synthesis see Scheme 3) were evaluated on isolated heart preparations of the guinea pig (left atrium and papillary muscle) for their effects on contractility and on refractory... 

Inhibits L-type Ca" channels in cardiac and vascular smooth muscle cells more selective for the myocardium with minimal vasodilatory effects compared with dihydropyridines class IV antiarrhythmic agents Inhibits L-type Ca " " channels in cardiac and vascular smooth muscle cells by modulating ion channel gating mechanisms decreases systemic blood pressure and heart contractility Binds with high affinity to the alpha2-delta subunit of voltagegated Ca " " channels in CNS anticonvulsant drug Inhibits neuronal fast Nay channels, and thus blocks the action potential inhibits also cardiac Nay channels... 

Equally as important, and potentially more clinically relevant, are the indirect mechanisms responsible for the antiarrhythmic activity of calcium inhibitory agents, including coronary vasodilation and subsequent increases in coronary artery blood flow (47, 114, 124, 157) decreased cardiac contractility, metabolism, and arterial vasodilation resulting in decreases in myocardial oxygen consumption and wall tension (92) and reflex alterations in autonomic regulation of heart rateToverdrive supression) and AV conduction (114) ... 

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