L-type calcium channel antagonism - Translation from in vitro to in vivo

摘要

Introduction: Although therapeutically beneficial in the treatment of certain diseases, L-type calcium channel antagonism can result in unwanted off-target pharmacology leading to adverse drug reactions and to the termination of the development of otherwise promising compounds. In the present study three marketed calcium channel inhibitors, nifedipine, verapamil and diltiazem were profiled in a series of in vitro and ex-vivo assays in an effort to determine the ability of these assays to discriminate, between dihydropyridine versus nondihydropyridine-like compounds, and how well they can predict the cardiovascular effects observed in a conscious telemetered rat model.