1,4-Dihydropyridines as calcium channel ligands and privileged structures

1. The 1,4-dihydropyridine nucleus serves as the scaffold for important cardiovascular drugs - calcium antagonists - including nifedipine, nitrendipine, amlodipine, and nisoldipine, which exert their antihypertensive and antianginal actions through actions at voltagegated calcium channels of the Ca_V1 (L-type) class. 2. These drugs act at a specific receptor site for which defined structure-activity relationships exist, including stereoselectivity. 3. Despite the widespread occurrence of the Ca_V1 of channel, the calcium antagonists exhibit significant selectivity of action in the cardiovascular system. This selectivity arises from a number of factors including subtype of channel, state-dependent interactions, pharmacokinetics, and mode of calcium mobilization. 4. The 1,4-dihydropyridine nucleus is also a privileged structure or scaffold that can, when appropriately decorated substituents, interact at diverse receptors and ion channels, including potassium and sodium channels and receptors of the G-protein class.