The 1,4-dihydropyridine nucleus: a pharmacophoric template part 1. Actions at ion channels.
The 1,4-dihydropyridine nifedipine is a prototypical example of the group of calcium channel blockers that also includes a number of second and third generation agents. These drugs enjoy substantial therapeutic prominence for their cardiovascular actions, including hypertension and angina. These actions are exerted at a specific member of the voltage-gated calcium channel family -the L-type channel. However, it is increasingly clear that the 1,4-dihydropyridine structure is a pharmacophoric template or "privileged structure" that, when appropriately substituted, can exert potent and selective actions at a diverse set of membrane receptors, including ion channels, G protein-coupled receptors and enzymes. This review will summarize the actions of 1,4-dihydropyridines at these receptors and advance the case that the 4-phenyl-1,4-dihydropyridine structure is a particularly versatile drug template. Part I of the review will summarize actions at ion channels and part II will summarize actions at other receptor systems.
Triggle
David J
DJ
State University of New York at Buffalo, Buffalo, NY 14260, USA. triggle@buffalo.edu
D002121:Calcium Channel Blockers / Q000737:chemistry* / Q000494:pharmacology*; D004095:Dihydropyridines / Q000737:chemistry* / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000378:metabolism*; D015394:Molecular Structure
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D007473:Ion Channels