Recent development in calcium channel antagonists.
The introduction of the Ca2+ channel antagonists, including the clinically available verapamil, nifedipine and diltiazem, into cardiovascular medicine served to initiate much work directed to the elucidation of their mechanisms of action at voltage-dependent Ca2+ channels. The Ca2+ channel ligands (both activator and antagonist) interact with the channel in a state-dependent manner associating preferentially with open states (activators) or open and inactivated states (antagonists). Both frequency- and voltage-dependent interactions occur with activator and antagonist drugs. These effects underlie the antiarrhythmic activity of verapamil and the vascular smooth muscle selectivity of 1,4-dihydropyridines. Selectivity of action occurs from a combination of factors including the relative Ca2+ demands of the system, the stimulus mode and state dependence of interaction, the agonist/antagonist character of the channel ligand and the category of Ca2+ channel involved.
Triggle
D J
DJ
School of Pharmacy, State University of New York, Buffalo.
Janis
R A
RA
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D013329:Structure-Activity Relationship
D002121:Calcium Channel Blockers; D015220:Calcium Channels