Document Detail


Cardiovascular effects of a new phenoxyalkylamine derivative, 2-isopropyl-5-[3-(2-methoxyphenoxy)propylamino]-2-(3,4,5-trimethoxy phenyl) valeronitrile fumarate (HV-525), in cross-circulated dog atrial preparations.
MedLine Citation:
PMID:  3599413     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A newly developed phenoxyalkylamine derivative, 2-isopropyl-5-[3-(2-methoxyphenoxy)propylamino]-2-(3,4, 5-trimethoxyphenyl)-valeronitrile fumarate (HV-525), was investigated in intact dogs and in isolated dog atria perfused with anesthetized donor dog's arterial blood. When 0.3 mg/kg of HV-525 was intravenously administered to the donor dog, a depressor effect without significant changes in heart rate was observed in donor dogs and a decrease in developed tension was observed in the isolated atrium. At 1 mg/kg, HV-525 caused a depressor response in donor dogs and decreases in developed tension and atrial rate in isolated atria. The decrease in systemic blood pressure seen following 1 mg/kg of HV-525 was between 15-40 mmHg. These effects continued for about 60 min. When HV-525 was administered into the cannulated sinus node artery of the isolated atrium, dose related negative inotropic and chronotropic actions were observed. Occasionally, HV-525 induced slight, brief positive chronotropic and inotropic effects followed by long-lasting negative effects. The threshold dose for inducing the negative chronotropic effect was approximately 3 micrograms while the negative inotropic one was approximately 1 microgram. A large dose of 100 micrograms of HV-525 caused a profound deceleration but not atrial arrest. The order of potencies for inducing a negative chronotropic effect in dog atria was verapamil greater than propranolol much greater than HV-525 greater than or equal to lidocaine greater than or equal to quinidine greater than phenytoin greater than disopyramide greater than procainamide, and that for inducing a negative inotropic effect was verapamil greater than or equal to propranolol greater than HV-525 greater than lidocaine greater than phenytoin greater than disopyramide greater than procainamide greater than or equal to quinidine. HV-525 did not induce a significant effect on sinoatrial conduction time. HV-525 at the doses studied, uniformly suppressed the frequency-force relationship, while verapamil, one of the phenoxyalkylamine derivatives, caused a marked depression of high frequency-induced contraction. Thus, it is concluded that HV-525 has mild depressant properties on the cardiovascular system and may have characteristics different from those of verapamil.
Authors:
S Chiba; Y Ogiwara; Y Furukawa; K Saegusa
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Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article    
Journal Detail:
Title:  Japanese heart journal     Volume:  28     ISSN:  0021-4868     ISO Abbreviation:  Jpn Heart J     Publication Date:  1987 Mar 
Date Detail:
Created Date:  1987-08-14     Completed Date:  1987-08-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0401175     Medline TA:  Jpn Heart J     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  261-72     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Arrhythmia Agents / pharmacology*
Cross Circulation*
Dogs
Dose-Response Relationship, Drug
Female
Heart / drug effects*
Heart Atria / drug effects
Heart Rate / drug effects
Male
Myocardial Contraction / drug effects
Parabiosis*
Perfusion / methods
Phenoxypropanolamines
Propylamines / pharmacology*
Sinoatrial Node / drug effects
Chemical
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 0/Phenoxypropanolamines; 0/Propylamines; 103545-91-1/HV 525

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


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