The group of compounds known as the CA++ channel antagonists and including the clinically available verapamil, nifedipine and diltiazem enjoy considerable pharmacologic and clinical attention. These agents and their analogs are believed to interact via a variety of mechanisms at voltage-dependent Ca++ channels. Several experimental approaches are planned to probe these Ca++ channels in smooth, cardiac and neuronal tissue. New Ca++ antagonists will be synthesised to investigate whether Ca++ channels can be differentiated into subtypes. The regulation of Ca++ channels including studies in developing and aging tissues, will be analysed. Through fluorescent analogs an attempt will be made to localize Ca++ channels. Possible changes in Ca++ and Ca++ antagonist sensitivity in the normo- and hypertensive state will be examined in several hypertensive models. An effort, will be made to synthesise """"""""site directed"""""""" Ca++ antagonists that will permit delivery of antagonists to specific receptors. Since their introduction into clinical medicine in North America, the available Ca++ antagonists have received considerable attention. Further understanding of their actions, as outlined here, will be of particular importance to the design of new and more selective agents.
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