Bepridil, calcium channel blocking

Funck-Brentano C, Chaffin PL, Wilkinson GR, McAllister B, Woosley RL. Effect of oral administration of a new calcium channel blocking agent, bepridil on antipyrine clearance in man. Br J Clin Pharmacol 1987 24(4) 559-60. 

Bepridil (59) blocks the slow calcium channel and serves as an antianginal agent and a vasodilator. In its synthesis, alcohol (derived from epichlorohydrin) is converted to the corresponding chloride with thionyl chloride and displaced with the sodium salt of ]i-benzylaniline to give bepridil (59) °... 

However, the reverse is not necessarily true all compounds that block the hERG channels do not prolong action potentials. Part of the reason lies in the fact that many compounds have a mixed effect on ion channels, particularly due to the blocking effect on both hERG and the L-type calcium channel [21], which is responsible for phase 2 of the cardiac action potential (Figure 16.1). Examples for such dual-blockers include bepridil, verapamil and mibefradil [22], all blocking hERG and L-type calcium channels at the therapeutic concentrations. However, only verapamil has nearly no cardiac liabilities. 

Important differences between the available calcium channel blockers arise from the details of their interactions with cardiac ion channels and, as noted above, differences in their relative smooth muscle versus cardiac effects. Cardiac sodium channels are blocked by bepridil but somewhat less effectively than are calcium channels. Sodium channel block is modest with verapamil and still less marked with diltiazem. It is negligible with nifedipine and other dihydropyridines. Verapamil and... 

Four categories of calcium channel blockers can be defined based on their chemical structures and actions diphenylalkylamines, benzothiazepines, dihydropyridines, and bepridil. Both diphenylalkylamines (verapamil) and benzothiazepines (diltiazem) exhibit effects on both cardiac and vascular tissue. With specificity for the heart tissue, these two types of calcium channel blockers can slow conduction through the AV node and are useful in treating arrhythmias. The dihydropyridines (nifedipine is the prototypical agent) are more potent peripheral and coronary artery vasodilators. They do not affect cardiac conduction, but can dilate coronary arteries. They are particularly useful as antianginal agents. Bepridil is unique in that it blocks both fast sodium channels and calcium channels in the heart. All calcium channel blockers, except nimodipine and bepridil, are effective in treating HTN. 

Members of the dihydropyridine class of calcium channel blocker drugs (e.g., nifedipine, nisoldipine) have intrinsically less effect on the cardiac conduction system than other classes. In particular, verapamil has a high degree of SA nodal and AV nodal blockade, and diltiazem has a somewhat lower effect. Bepridil blocks both sodium and potassium channels, and also causes both SA nodal and AV nodal blockade. 

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