Negative chronotropic but no antiarrhythmic effect of (+)- and (-)-naloxone in rats and guinea pigs.
OBJECTIVE
The aim was to investigate the antiarrhythmic effects of (+)- and (-)-naloxone in various arrhythmia models in vivo.


METHODS
Naloxone (1-40 mg.kg-1), naltrexone (20-40 mg.kg-1), or standard antiarrhythmic drugs (quinidine, lignocaine, phenytoin, (+)-sotalol) were injected intravenously. Ventricular extrasystoles were then elicited by infusion of either ouabain (guinea pigs) or aconitine (rats), or by electrical stimulation (guinea pigs).


METHODS
Male Wistar rats and guinea pigs (n = 6-10) were used. Arterial blood pressure and ECG were recorded continuously.


RESULTS
Naloxone and naltrexone decreased the heart rate. The effect of naloxone was not stereospecific and is apparently not mediated by opioid receptors. Naloxone had no influence on ouabain induced arrhythmias or fibrillation threshold in guinea pigs. The appearance of aconitine induced extrasystoles was accelerated by 20 mg.kg-1 (-)-naloxone but delayed by 40 mg.kg-1. No effects were seen with (+)-naloxone or (-)-naltrexone.


CONCLUSIONS
The results show that naloxone does not possess prominent antiarrhythmic properties.
Kaschube
M
M
Department of Pharmacology, Medical University of Lübeck, Germany.
Brasch
H
H
D000157:Aconitine; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D003864:Depression, Chemical; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009270:Naloxone / Q000627:therapeutic use*; D009271:Naltrexone / Q000627:therapeutic use; D010042:Ouabain; D051381:Rats; D013237:Stereoisomerism
D000889:Anti-Arrhythmia Agents; D009270:Naloxone; D010042:Ouabain; D009271:Naltrexone; D000157:Aconitine