Antiarrhythmic effects of U-50,488H in rats subject to coronary artery occlusion.
The antiarrhythmic actions of low and high doses of U-50,488H, a selective kappa-receptor agonist, were examined in pentobarbitone-anaesthetized rats subjected to occlusion of the left anterior descending coronary artery. At a high dose (16 mumol/kg) U-50,488H reduced blood pressure, heart rate and prolonged the P-R and QRS intervals of the electrocardiogram. This dose reduced the incidence of ventricular arrhythmias produced by occlusion. The blood pressure, heart rate, ECG and antiarrhythmic actions of a high dose of U-50,488H were not antagonized by 8 mumol/kg naloxone, a dose which had no cardiovascular or ECG actions. Naloxone alone reduced arrhythmia incidence but to a lesser extent than U-50,488H. A low dose (0.2 mumol/kg) of U50,488H in the absence or presence of naloxone had no effect on arrhythmias. Thus, U-50,488H had antiarrhythmic actions at a high dose which were independent of opioid receptors.
Pugsley
M K
MK
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Penz
W P
WP
Walker
M J
MJ
Wong
T M
TM
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000503:physiopathology; D001262:Atenolol / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D011188:Potassium / Q000097:blood; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains
D000889:Anti-Arrhythmia Agents; D011759:Pyrrolidines; D009270:Naloxone; D001262:Atenolol; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D011188:Potassium