Document Detail

Failure to reproduce the in vitro cardiac electrophysiological effects of naloxone in humans.
MedLine Citation:
PMID:  8198939     Owner:  NLM     Status:  MEDLINE    
1. Opioid receptor antagonists such as naloxone have shown antiarrhythmic activity in animal models of coronary artery occlusion. Studies have indicated that these effects are stereospecific but both isomers of naloxone prolong action potential duration and refractoriness in guinea-pig and rabbit isolated ventricular myocardium (Class III effect). 2. This study was performed to identify whether this Class III effect of naloxone could be reproduced in human myocardium in vivo. Twenty patients with coronary artery disease received intravenous racemic naloxone (1-40 micrograms kg-1 min-1). Surface electrocardiographic parameters were measured and refractory periods were determined during fixed rate pacing by programmed stimulation. 3. The corrected QT interval during sinus rhythm (SR-QTc) was prolonged by 5(3)% (P = 0.06) at a dose of 20 micrograms kg-1 min-1 and by 9(10)% at 40 micrograms kg-1 min-1 (P = 0.03). These small changes were lost at higher paced heart rates. No significant effects on atrial, atrioventricular nodal or ventricular refractoriness were seen. 4. Plasma naloxone concentrations well into the micromolar range were achieved with both of the higher doses of naloxone administered. Plasma beta-endorphin concentrations invariably increased following naloxone infusion. There was no statistical relationship between peak plasma naloxone concentrations and the absolute or percent prolongation of SR-QTc. 5. It seems unlikely that racemic naloxone would have any clinical utility as an antiarrhythmic agent. Racemic naloxone may enhance cardiac adrenergic nerve activity and this receptor mediated effect may have prevented the demonstration of any nonreceptor mediated prolongation of cardiac refractoriness. Studies with the individual stereoisomers of naloxone would be of interest.
K G Oldroyd; A C Rankin; C E Gray; K Harvey; W Borland; A P Rae; S M Cobbe
Related Documents :
11320459 - Qt and jt dispersion in patients with monomorphic or polymorphic ventricular tachycardi...
9817559 - Severe and early alteration of action potential during acute cardiac rejection in rats.
23111649 - Echocardiographic evaluation of asymptomatic patients affected by rheumatoid arthritis.
12586249 - Effects of acute myocardial ischemia on qt dispersion by dipyridamole stress echocardio...
7977069 - Variability of qt dispersion measurements in the surface electrocardiogram in patients ...
6833919 - Effects of hyperkalemia on local changes of repolarization duration in canine left vent...
16759719 - Whole heart coronary magnetic resonance angiography for the detection of coronary arter...
16138919 - Complications during pharmacological stress echocardiography: a video-case series.
7594079 - Left ventricular beat-to-beat performance in atrial fibrillation: contribution of frank...
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  British journal of clinical pharmacology     Volume:  37     ISSN:  0306-5251     ISO Abbreviation:  Br J Clin Pharmacol     Publication Date:  1994 Mar 
Date Detail:
Created Date:  1994-07-07     Completed Date:  1994-07-07     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7503323     Medline TA:  Br J Clin Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  289-94     Citation Subset:  IM    
Department of Medical Cardiology, Royal Infirmary, Glasgow, UK.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Action Potentials / drug effects
Coronary Disease / physiopathology*
Electrocardiography / drug effects*
Heart Rate / drug effects
Injections, Intravenous
Naloxone / administration & dosage,  blood,  pharmacology*,  therapeutic use
beta-Endorphin / blood*
Reg. No./Substance:
465-65-6/Naloxone; 60617-12-1/beta-Endorphin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Trimetazidine: a new concept in the treatment of angina. Comparison with propranolol in patients wit...
Next Document:  Cefpiramide kinetics and plasma protein binding in cholestasis.