Effects of promethazine on ischemic and reperfusion arrhythmias in rat heart.
The effects of the H1-receptor antagonists promethazine, mepyramine, and chlorpheniramine on ischemic and reperfusion arrhythmias were studied in the isolated perfused rat heart. Promethazine reduced both ischemic and reperfusion arrhythmias (2 x 10(-6)M-7.5 x 10(-6)M). Mepyramine and chlorpheniramine decreased these arrhythmias but at concentrations about 10 times higher. The H2-blockers cimetidine and ranitidine had no antiarrhythmic effect. Promethazine also: (i) increased release of noradrenaline by the heart; and (ii) increased coronary flow in the reperfusion period and in some mildly ischemic zones. It is proposed that promethazine exerts most of its antiarrhythmic effects by a nonspecific mechanism, possibly membrane stabilization; in addition, enhanced coronary flow may play a role.
Rochette
L
L
Laboratoire de Pharmacodynamie et Physiologie Pharmaceutique, Université de Dijon, France.
Yao-Kouame
J
J
Bralet
J
J
Opie
L H
LH
D000818:Animals; D000889:Anti-Arrhythmia Agents; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control*; D002744:Chlorpheniramine / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D003327:Coronary Disease / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D010477:Perfusion; D011398:Promethazine / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D006634:Histamine H1 Antagonists; D011725:Pyridines; D011969:Receptors, Histamine H1; D002744:Chlorpheniramine; D002927:Cimetidine; C006183:2-(2-aminoethyl)pyridine; D011398:Promethazine