Sites, mechanisms of action, and differentiation of calcium channel antagonists

The calcium channel antagonists are a chemically heterogeneous group of agents that includes verapamil, nifedipine, and diltiazem as first-generation agents. They owe their effectiveness to interactions at specific sites associated with a major protein of the L class of voltage-gated channel. The calcium channel may be viewed as a pharmacologic receptor, with specific sites for activator and antagonist ligands that are linked to the functional machinery of the channel. These sites are subject to homologous and heterologous regulation and a number of disease states--both experimental and clinical--alter their expression. The selective actions of these agents are reviewed from several perspectives, particularly that of voltage-dependent interactions that distinguish between cells according to membrane potential and other factors.