Voltage-dependent calcium channels: structures and drug-binding sites.

I47 Tsien’s group classified these channels as ‘N, ‘T, In the 1960s the research groups of Fleckenstein and Godfraind defined ‘calcium antagonists’ as agents which blocked the entry of calcium into cells via voltage-dependent calcium channels. In a literature search we found 74 compounds in various stages of clinical or preclinical development classed as ‘calcium antagonists’. Since the initial work of Fleckenstein [ l ] and Godfraind et al. [2], it has become apparent that there are many different types of calcium channel, that there are different binding sites for drugs on the various channels, and that the binding of some of the drugs is highly voltage-dependent, allowing selective interactions with certain states of the channels and selective therapeutic interventions. The application of molecular biology has resulted in the definition of the primary structure of many subtypes of the calcium channel and the first steps are being made to define the structure of the drug receptor sites on the channel proteins.