Effects of KT-362, a new calcium release blocker, on vascular selectivity and hemodynamic actions in anesthetized dogs

Japanese Journal of Pharmacology
S WakabayashiS Shibata

Abstract

Pharmacological properties of 5-(3-((2-(3,4-dimethoxyphenyl)ethyl)-amino)-1- oxopropyl)-2,3,4,5-tetrahydro-1,5-benzothiazepine fumarate (KT-362), a newly synthesized calcium release blocker, were studied by comparing its vascular selectivity and cardiovascular actions with those of verapamil, a calcium entry blocker. The relaxing effect of KT-362 in rabbit femoral and basilar artery strips contracted with norepinephrine was greater than that in aortic and coronary artery strips. In anesthetized mongrel dogs, KT-362 (0.1-3.0 mg/kg, i.v.) decreased the mean blood pressure, heart rate and total peripheral resistance in a dose-dependent manner, while cardiac output increased slightly despite a decrease in left ventricular pressure. This is consistent with the data on verapamil. Both i.a. and i.v. injections of KT-362 produced a marked dose-dependent increase in vertebral and femoral blood flow. Pretreatment of atropine, propranolol or diphenhydramine exerted no significant effect on the KT-362-induced vasodilation. Verapamil caused a marked increase in the vertebral and coronary blood flows after the injections, but only a slight increase in femoral blood flow. KT-362 at the dose of 10 mg/kg, i.v., had no significant effect on the ...Continue Reading

Related Concepts

5-(3-((2-(3,4-dimethoxyphenyl)ethyl)amino)-1-oxopropyl)-2,3,4,5-tetrahydro-1,5-benzothiazepine fumarate
Anesthesia, Intravenous
Metazoa
Structure of Basilar Artery
Calcium Channel Blockers
Canis familiaris
Electrocardiographic Recorders
Structure of Femoral Artery
Hemodynamics
Intravenous Injections

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