Document Detail

Electrophysiological effects of clentiazem, a new Ca2+ antagonist, on rabbit hearts.
MedLine Citation:
PMID:  8859929     Owner:  NLM     Status:  MEDLINE    
Electrophysiological effects of clentiazem, a new 1,5-benzothiazepine type Ca(2+) antagonist, were examined in comparison with those of diltiazem in excised rabbit heart preparations. In Langendorff-perfused hearts electrically driven at basic cycle lengths of 400-500 ms, clentiazem (10(-8)-10(-6)M) and diltiazem (10(-8)-10(-6)M) caused a concentration-dependent prolongation of the atrio-His bundle conduction time (A-H interval) without affecting the His bundle-ventricular conduction time (H-V interval). The effects of clentiazem were equivalent to those of diltiazem. In isolated rabbit atrioventricular (A-V) node preparations electrically driven at 400- to 500-ms intervals, clentiazem and diltiazem at >10(-6)M concentrations produced concentration-dependent decreases in action potential amplitude (APA), maximum rate of depolarization (V max), and shortened action potential duration at 20 and 50% repolarization (APD(20) and APD(50)), whereas APD(90) was little affected. Application of 10(-6)M clentiazem prolonged effective refractory period (ERP) of the A-V node by approximately 7% of the control, an effect similar to that of diltiazem. In spontaneously beating sinoatrial (S-A) node preparations, clentiazem l0(-6)M or the higher concentration significantly decreased APA, V(max), and slope of slow diastolic depolarization, while reducing the maximum diastolic potential. The inhibitory effects of clentiazem showed strong suppression of APA and V(max) by 31.1 and 47.2% of the control, respectively, whereas both clentiazem (10(-7)-10(-5)M) and diltiazem (10(-7)-10(-5)M) had no effects on parameters of ventricular APs. These results suggest that dentiazem, like diltiazem, has a preferential inhibitory action on cardiac slow Ca(2+) channels.
K Miyazaki; H Adaniya; T Sawanobori; M Hiraoka
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  27     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1996 May 
Date Detail:
Created Date:  1997-04-10     Completed Date:  1997-04-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  615-21     Citation Subset:  IM    
Department of Cardiovascular Diseases, Medical Research Institute, Tokyo Medical and Dental University, Yushima, Tokyo, Japan.
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MeSH Terms
Action Potentials / drug effects
Calcium Channel Blockers / pharmacology*
Diltiazem / analogs & derivatives*,  pharmacology
Heart Conduction System / drug effects*,  physiology
Reg. No./Substance:
0/Calcium Channel Blockers; 111659-76-8/clentiazem; 42399-41-7/Diltiazem

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