Effects of calcium antagonist, 6-(N, N-diethylamino) hexyl-3, 4, 5-trimethoxybenzoate, on digitalis-induced arrhythmias and cardiac contractions.
6-(N, N-Diethylamino) hexyl-3, 4, 5-trimethylbenzoate (TMB-6) and lidocaine were equipotent (1 mg/kg) in the conversion of ectopic rhythms to normal rhythms in digoxin-toxic dogs. However, TMB-6 had fewer side effects on heart rates and dp/dt than lidocaine. TMB-6 inhibited the contractile force of electrically stimulated dog and guinea-pig atria and ventricles at concentrations ranging from 2.5 X 10(-5) to 1.7 X 10(-4) M. Elevation of extracellular Ca++ concentrations from 2.7 to 5.4 mM produced a significant increase in the ID50 of TMB-6 in atria (from 2.5 X 10(-5) to 5.0 X 10(-5) M in dogs and from 7.2 X 10(-5) to 1.0 X 10(-4) M in guinea pigs). TMB-6 (7.3 X 10(-5) to 2.4 X 10(-4) M) depressed the amplitude of Ca++-dependent action potentials in depolarized dog cardiac Purkinje fibers. These results are discussed with regard to the antagonism of TMB-6 on Ca++ availability in the myocardium which leads to the conversion of cardiac arrhythmias.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy*; D002118:Calcium / Q000037:antagonists & inhibitors*; D004071:Digitalis Glycosides / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011690:Purkinje Fibers / Q000187:drug effects; D013997:Time Factors
D004071:Digitalis Glycosides; C012618:TMB 6; D005707:Gallic Acid; D008012:Lidocaine; D002118:Calcium