Document Detail


Electrophysiological effects of dronedarone (SR 33589), a noniodinated amiodarone derivative in the canine heart: comparison with amiodarone.
MedLine Citation:
PMID:  11429385     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The electrophysiological effects of dronedarone, a new nonionidated analogue of amiodarone were studied after chronic and acute administration in dog Purkinje fibres, papillary muscle and isolated ventricular myocytes, and compared with those of amiodarone by applying conventional microelectrode and patch-clamp techniques. Chronic treatment with dronedarone (2x25 mg(-1) kg(-1) day p.o. for 4 weeks), unlike chronic administration of amiodarone (50 mg(-1) kg(-1) day p.o. for 4 weeks), did not lengthen significantly the QTc interval of the electrocardiogram or the action potential duration (APD) in papillary muscle. After chronic oral treatment with dronedarone a small, but significant use-dependent V(max) block was noticed, while after chronic amiodarone administration a strong use-dependent V(max) depression was observed. Acute superfusion of dronedarone (10 microM), similar to that of amiodarone (10 microM), moderately lengthened APD in papillary muscle (at 1 Hz from 239.6+/-5.3 to 248.6+/-5.3 ms, n=13, P<0.05), but shortened it in Purkinje fibres (at 1 Hz from 309.6+/-11.8 to 287.1+/-10.8 ms, n=7, P<0.05). Both dronedarone (10 microM) and amiodarone (10 microM) superfusion reduced the incidence of early and delayed afterdepolarizations evoked by 1 microM dofetilide and 0.2 microM strophantidine in Purkinje fibres. In patch-clamp experiments 10 microM dronedarone markedly reduced the L-type calcium current (76.5+/-0.7 %, n=6, P<0.05) and the rapid component of the delayed rectifier potassium current (97+/-1.2 %, n=5, P<0.05) in ventricular myocytes. It is concluded that after acute administration dronedarone exhibits effects on cardiac electrical activity similar to those of amiodarone, but it lacks the 'amiodarone like' chronic electrophysiological characteristics.
Authors:
A Varró; J Takács; M Németh; O Hála; L Virág; N Iost; B Baláti; M Agoston; A Vereckei; G Pastor; M Delbruyère; P Gautier; D Nisato; J G Papp
Related Documents :
19190125 - Developmental exposure to chlorpyrifos induces alterations in thyroid and thyroid hormo...
10442215 - Effects of storage and cooking on the iodine content in iodized salt and study on monit...
1608915 - Thyroid status and hepatic thyroxine deiodinating activity under high-dose long-term ni...
1265085 - Inhibitory effect of large doses of propylthiouracil and methimazole on an increase of ...
18292435 - The effect of thoracic epidural bupivacaine and an intravenous adrenaline infusion on g...
19655825 - Safety of the combination of intensive cholesterol-lowering therapy with oral anticoagu...
Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  133     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2001 Jul 
Date Detail:
Created Date:  2001-06-28     Completed Date:  2001-08-09     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  625-34     Citation Subset:  IM    
Affiliation:
Department of Pharmacology & Pharmacotherapy, Faculty of Medicine, University of Szeged, Dóm tér 12, H-6701 Szeged, Hungary.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Action Potentials / drug effects
Amiodarone / analogs & derivatives*,  blood,  chemistry,  pharmacology*
Animals
Dogs
Electric Stimulation
Electrocardiography
Electrophysiology
Female
Heart Ventricles / cytology,  drug effects*
Male
Papillary Muscles / drug effects,  physiology
Purkinje Fibers / drug effects,  physiology
Vasodilator Agents / pharmacology*
Ventricular Function
Chemical
Reg. No./Substance:
0/Vasodilator Agents; 1951-25-3/Amiodarone; JQZ1L091Y2/dronedarone; M31FU99E3Y/desethylamiodarone
Comments/Corrections

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


Previous Document:  Nitric oxide- and nitric oxide donors-induced relaxation and its modulation by oxidative stress in p...
Next Document:  Role of protein kinase C in the reduction of infarct size by N-methyl-1-deoxynojirimycin, an alpha-1...