CEREBROVASCULAR EFFECTS OF YC-93, A NEW VASODILATOR, IN DOGS, MONKEYS AND HUMAN PATIENTS

Abstract

Cerebrovascular effects of YC-93 [2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-[2-(N-benzyl-N-methylamino)]ethyl ester 5-methyl ester hydrochloride], a new 1,4-dihydropyridine derivative, was examined in experimental animals and in human patients using a variety of methods. YC-93 in doses ranging from 0.001-0.03 mg/kg i.v. increased regional cerebral cortical blood flow and cerebral venous outflow in anesthetized dogs and internal carotid blood flow in anesthetized monkeys. The increase in cerebral blood flow was accompanied by an increase in O2 delivery to the brain and an elevation of CSF pressure. Both intracarotid injection and intraduodenal administration of YC-93 caused cerebral vasodilation in monkeys. In patients with cerebrovascular diseases and other chronic diseases, measurements of cerebral blood flow by the 133Xe clearance method showed that an intracarotid injection of 1 .mu.g/kg of YC-93 increased cerebral blood flow by 28.8% without changing arterial blood pressure and arterial p[partial pressure]CO2 and that an injection of 0.01 mg/kg of YC-93 increased cerebral blood flow by 17.0% with a minimal decrease in the arterial blood pressure but without changing arterial pCO2. YC-93 produced a potent cerebral vasodilation in experimental animals and in human patients in the same dose and may act directly on the cerebral vascular beds.