Potential-Dependent Interactions of Nitrendipine and Related 1,4-Dihydropyridines in Functional

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Abstract
Interaction of nitrendipine and other Ca2+ channel antagonists including nifedipine, diltiazem, and D600 with intestinal smooth muscle was shown to depend on membrane potential. In the absence of extracellular Ca2+, guinea pig ileal longitudinal muscle does not contract and can be incubated at various K+ concentrations in the presence or absence of antagonist. Preincubation with elevated K+ prior to admission of Ca2+ and challenge with K+ to a total of 100 mM increased the activity of the antagonist. The IC50 for nitrendipine incubated in the presence of 5 mM K+ was 5.36 × 109M and in the presence of 40 mM K+ was 0.53 109M. Other 1.4-dihydropyridmes showed similar potency shifts.

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