Mechanisms of action of calcium entry blockers.

This review is focused on experimental observations that permit conclusions about the mechanism of action of calcium entry blockers. It is shown that studies on the blockade of contraction (or relaxation) of depolarized smooth muscle must be confirmed by direct estimates of calcium fluxes. Superimposition of dose-inhibition curves of contraction and 45Ca entry are a prerequisite for allowing a drug to be regarded as a specific calcium entry blocker. Among the main characteristics of such drugs are their tissue selectivity and use dependency in depolarized preparations. It is shown that one of these (flunarizine) interacts with binding sites located in the plasma membrane possibly associated with the calcium channels. The physiological role of calcium and possible therapeutic uses of calcium entry blockers are also summarized.