Document Detail


Pharmacological studies on a new antihypertensive agent, S-2150, a benzothiazepine derivative: 1. Antinecrotic and antiarrhythmic effects in reperfused rat hearts.
MedLine Citation:
PMID:  8891877     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
S-2150 is a new 1,5-benzothiazepine derivative that inhibits [3H]diltiazem and [3H]WB4101 bindings to the membrane of rat tissue. The effects of S-2150 on ischemia/ reperfusion injury were studied in anesthetized rats. S-2150 reduced the myocardial infarct size (IS) induced by 20-min coronary artery occlusion followed by reperfusion. To evaluate reperfusion-induced ventricular tachycardia and fibrillation (VT, VF), we occluded the coronary artery for 4 min and then reperfused it. The incidence of arrhythmia was blocked by S-2150, and this effect offered protection against cardiac death. Prazosin did not modify the IS or incidence of reperfusion arrhythmias, but combined treatment with a noneffective dose of diltiazem showed significant cardioprotective effects. We also compared the direct effects of S-2150 and diltiazem on cardiac function and coronary perfusion flow using isolated rat hearts. Both drugs decreased mechanical function and increased coronary flow, with S-2150 being less cardiodepressive and more vasodilatory. S-2150 is cardioprotective at doses comparable to hypotensive doses even though its cardiodepressant effect is much weaker than that of diltiazem. This effectiveness may be partly explained by its dual characteristics: blocking the Ca channel and the alpha 1-adrenoceptor.
Authors:
M Masui; S Funakawa; O Uno; S Mihara; Y Takahara; K Matsunaga; K Iwaki
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Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  28     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1996 Oct 
Date Detail:
Created Date:  1997-03-24     Completed Date:  1997-03-24     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  526-32     Citation Subset:  IM    
Affiliation:
Discovery Research Laboratories II, Shionogi & Company, Osaka, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic alpha-Antagonists / pharmacology
Animals
Anti-Arrhythmia Agents / pharmacology*
Arrhythmias, Cardiac / etiology,  prevention & control
Calcium Channel Blockers / pharmacology*
Coronary Circulation / drug effects
Creatine Kinase / metabolism
Diltiazem / administration & dosage,  analogs & derivatives*,  antagonists & inhibitors,  pharmacology
Drug Therapy, Combination
Heart / drug effects*,  physiopathology
Male
Myocardial Reperfusion Injury / complications,  prevention & control*
Necrosis
Prazosin / antagonists & inhibitors,  pharmacology
Protein Binding / drug effects
Rats
Rats, Wistar
Vasodilator Agents / pharmacology
Chemical
Reg. No./Substance:
0/Adrenergic alpha-Antagonists; 0/Anti-Arrhythmia Agents; 0/Calcium Channel Blockers; 0/S 2150; 0/Vasodilator Agents; 19216-56-9/Prazosin; 42399-41-7/Diltiazem; EC 2.7.3.2/Creatine Kinase

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


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