Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
-
Animals
-
Anti-Arrhythmia Agents / administration & dosage
-
Anti-Arrhythmia Agents / pharmacology
-
Anti-Arrhythmia Agents / therapeutic use*
-
Arrhythmias, Cardiac / drug therapy*
-
Arrhythmias, Cardiac / physiopathology
-
Atenolol / pharmacology
-
Blood Pressure / drug effects*
-
Coronary Disease / drug therapy*
-
Coronary Disease / physiopathology
-
Dose-Response Relationship, Drug
-
Drug Interactions
-
Electrocardiography
-
Heart Rate / drug effects*
-
Male
-
Naloxone / pharmacology
-
Potassium / blood
-
Pyrrolidines / administration & dosage
-
Pyrrolidines / pharmacology
-
Pyrrolidines / therapeutic use*
-
Rats
-
Rats, Inbred Strains
Substances
-
Anti-Arrhythmia Agents
-
Pyrrolidines
-
Naloxone
-
Atenolol
-
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
-
Potassium