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1,4‐Dihydropyridine Ca 2+ channel antagonists and activators: A comparison of binding characteristics with pharmacology
Author(s) -
Janis Ronald A.,
Triggle David J.
Publication year - 1984
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430040304
Subject(s) - dihydropyridine , chemistry , binding site , biophysics , dissociation constant , vascular smooth muscle , pharmacology , cardiac muscle , mechanism of action , stereochemistry , cardiac action potential , receptor , electrophysiology , biochemistry , smooth muscle , calcium , medicine , endocrinology , in vitro , biology , repolarization , organic chemistry
This comparison of the binding characteristics and pharmacology of 1,4‐dihydropyridines indicates that the high‐affinity binding sites studied in cardiac and smooth muscle cells represent a major site of action of these drugs, and that this site is the Ca 2+ channel or a closely related protein. Electrophysiological studies suggest that the effects of both Ca 2+ channel inhibitors and activators are voltage dependent. The apparent lack of agreement between the equilibrium dissociation constants for [ 3 H]1,4‐dihydropyridines and their potency in cardiac muscle may be due to conformational modifications that occur in the 1,4‐dihydropyridine binding site as a result of voltage or other changes during membrane isolation. The selective effect of 1,4‐dihydropyridines for vascular smooth muscle relative to cardiac muscle may be explained, in part, by differences in membrane potentials and Ca 2+ channel regulatory mechanisms and, in part, by differences in receptor structure. 1,4‐Dihydropyridine antagonists and activators appear to bind to a common site that is not the same as the binding site for nondihydropyridine Ca 2+ channel antagonists.