Anti-arrhythmic activities of opioid agonists and antagonists and their stereoisomers.
1. A series of opioid agonists, antagonists and their (+)-stereoisomers were tested for antiarrhythmic activity in the rat coronary artery occlusion model. 2. Naloxone (0.01-2 mg kg-1) significantly reduced the incidence and severity of cardiac arrhythmias, in accordance with previous published studies. 3. The non-opioid stereoisomer, (+)-naloxone, was equipotent with naloxone against occlusion-induced arrhythmia. 4. Similar non-stereospecific antiarrhythmic effects were induced by another opioid antagonist, Win 44,441-3 and its stereoisomer Win 44,441-2. 5. The opioid agonists, morphine and levorphanol, protected against occlusion-induced arrhythmia as did the opioid antagonists, and the (+)-stereoisomer, dextrorphan, was equipotent to levorphanol. 6. It is concluded that the antiarrhythmic effects of opioid drugs are not mediated by opioid receptors. A direct effect on ionic currents in cardiac muscle is suggested as the mechanism of opioid antiarrhythmic activity.
Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Israel.
Y
Y
Sarne
A
A
Flitstein
E
E
Oppenheimer
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001392:Azocines / Q000494:pharmacology*; D007981:Levorphanol / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D051381:Rats; D013237:Stereoisomerism
D000889:Anti-Arrhythmia Agents; D001392:Azocines; D009292:Narcotic Antagonists; D007981:Levorphanol; D009270:Naloxone; D009020:Morphine; C035969:quadazocine