Molecular pharmacology of non-L-type calcium channels

Voltage-gated calcium channels are key sources of calcium entry into the cytosol. Mutations in calcium channels have been implicated in numerous disorders such as migraine, incomplete congenital X-linked stationary night blindness, epilepsy, and ataxia, and they are important therapeutic targets for the treatment of pain, stroke, hypertension, and epilepsy. Calcium channel antagonists can be broadly classified into three groups. 1) Inorganic ions typically nonselectively block the pore of most calcium channel subtypes, and in some cases, alter gating kinetics. 2) Peptides isolated from arachnids, cone snails, and snakes frequently selectively antagonize individual calcium channel subtypes by direct occlusion of the pore or altering gating kinetics. 3) Small organic molecules of various structure-activity-relationship (SAR) classes can mediate both selective and nonselective effects on individual calcium channel subtypes, and occlude the pore or reduce channel availability. Here, we provide an overview of classes of inhibitors of non-L-type calcium channels.