Abstract

The Ca2+ channel blockers represent a successful group of therapeutic agents directed against cardiovascular targets, including hypertension and angina. These drugs, including the first-generation verapamil, nifedipine and diltiazem are directed against a subclass of voltage-gated Ca2+ channel - the L-type channel. Other subclasses of Ca2+ channel exist and are targets for new indications. The mechanisms of actions of the L-type blockers are discussed and the origins of their cardiovascular selectivity discussed. Although new drugs of this class directed against hypertension could be developed, there are both clinical and economic reasons that argue against such development. However, there are other possible targets to investigate where antagonists and activators of the L-type channel may be useful: such targets include fertility, neuronal growth, bone formation and epilepsy. Limitations to these approaches are discussed.

Keywords: Ca2+ channels, Ca2+ channel blockers, hypertension, angina, arrhythmias, neuronal Ca2+ channels, verapamil, diltiazem, nifedipine, 1, 4-dihydropyridines