Abstract
Effects of ifenprodil (2-(4-benzyl-piperidino)-1-(4-hydroxyphenyl)-1-propanol) tartrate on the cardiovascular system were studied in mongrel dogs anesthetized with pentobarbital sodium and with alpha-chloralose and in rabbits. Ifenprodil (12.5 to 5,000 mug/kg i.v.) lowered systemic blood pressure in a dose-dependent manner in association with increased heart rate and augmented myocardial contractile force in dogs. Fall in blood pressure and tachycardia caused by ifenprodil were inhibited by pretreatment with phenoxybenzamine (5 mg/kg). The pressor responses to adrenaline and bilateral carotid occlusion were moderately reduced by pretreatment with ifenprodil (5 mg/kg), while the response to noradrenaline was attenuated only slightly. Ifenprodil (less than 1 mg/kg i.v.) decreased the total peripheral resistance and resistances of common carotid, internal carotid, vertebral, coronary, superior mesenteric, renal and femoral vascular beds in dogs. Ifenprodil increased the vertebral and femoral blood flow consistently (93.6 and 174.0%, respectively) but decreased the renal blood flow. Intra-arterial injection of ifenprodil (0.01 to 5 mug/kg) produced a dose-dependent increase in blood flow of vascular beds tested. The femoral and vertebral arterial blood flows were in particular consistently increased. Increases in the vertebral and femoral blood flows following i.v. and i.a. injections of ifenprodil were only slightly attenuated by pretreatment with phenoxybenzamine. Intravenous injections of ifenprodil (12.5 to 5,000 mug/kg) produced tachycardia in conscious rabbits but caused bradycardia after pretreatment with reserpine. From these results it was revealed that ifenprodil causes a fall in systemic blood pressure and an increase in the blood flow particularly in vertebral and femoral vasculatures following the vasodilating action directly on vascular smooth muscle. Blocking action of alpha-adrenoceptors in vessels was also demonstrated.
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