Cardiovascular effects of a new phenoxyalkylamine derivative, 2-isopropyl-5-(3-(2-methoxyphenoxy)propylamino)-2-(3,4,5-trimethoxyphenyl)valeronitrile fumarate (HV-525), in cross-circulated dog atrial preparations.
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概要
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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 0.3mg/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 1mg/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 1mg/kg of HV-525 was between 15-40mmHg. These effects continued for about 60min. 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 3μg while the negative inotropic one was approximately 1μg. A large dose of 100μg 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>propranolol>HV-525_??_lidocaine_??_quinidine>phenytoin>disopyramide>procainamide, and that for inducing a negative inotropic effect was verapamil_??_propranolol>HV-525>lidocaine>phenytoin>disopyramide>procainamide_??_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.
- International Heart Journal刊行会の論文
著者
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Furukawa Yasuyuki
Department Of Pharmacology Shinshu University School Of Medicine
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Chiba Shigetoshi
Departmen T Of Pharmacology Shinshu University School Of Medicine
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SAEGUSA Kimiaki
Department of Pharmacology and Research Laboratory for Cardiovascular Diseases, Shinshu University School of Medicine
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OGIWARA Yasuhiro
Department of Pharmacology, Shinshu University School of Medicine
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