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Comparison of negative inotropic potency, reversibility, and effects on calcium influx of six calcium channel antagonists in cultured myocardial cells
Author(s) -
Barry W.H.,
Horowitz J.D.,
Smith Thomas W.
Publication year - 1985
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1985.tb08830.x
Subject(s) - verapamil , diltiazem , nifedipine , calcium channel , calcium , inotrope , chemistry , contractility , pharmacology , potency , medicine , endocrinology , calcium channel blocker , voltage dependent calcium channel , in vitro , biochemistry
1 The negative inotropic effects of calcium channel antagonists on the myocardium were used as a standard for the definition and determination of potency of this group of drugs. 2 The effects of six calcium channel antagonists (verapamil, methoxyverapamil (D600), nifedipine, lidoflazine, perhexiline and diltiazem) were compared on cultured chick embryo ventricular cells. 3 Drug concentrations producing 50% inhibition of contractile amplitude, derived from linearized concentration‐response curves, varied from 2.8 × 10 −8 M for nifedipine to 8.3 × 10 −7 M for perhexiline. Equipotent negative inotropic concentrations of verapamil, D600, perhexiline, diltiazem and lidoflazine produced a similar inhibitory effect on 45 Ca uptake into cultured cells. Nifedipine produced no significant inhibition of 45 Ca uptake. 4 The time required for recovery of contractility after cessation of drug superfusion varied in the order lidoflazine > perhexiline >D600> verapamil > nifedipine > diltiazem. This relative order accords closely with the reported in vivo half‐lives of these drugs. 5 It is concluded that while some inhibition of 45 Ca 2+ uptake into cardiac cells can be demonstrated with five of the six calcium channel blockers studied, the relationship between the degree of inhibition of calcium influx and negative inotropic effects may not be uniform for all calcium channel antagonists.