The 1,4-Dihydropyridine Nucleus: A Pharmacophoric Template Part 1. Actions at Ion Channels
David J. Triggle
Affiliation: School of Pharmacy andPharmaceutical Sciences, 463 Hochstetter Hall, State University of NewYork, Buffalo, NY 14260. USA
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.
Keywords: 1,4-Dihydropyridine, nifedipine, calcium channel
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