Cerebrovascular effects of YC-93, a new vasodilator, in dogs, monkeys and human patients.

Cerebrovascular effects of YC-93, 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 to 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 oxygen delivery to the brain and an elevation of cerebrospinal fluid pressure. Both intracarotid injection and intraduodenal administration of YC-93 also resulted in cerebral vasodilation in monkeys. In patients with cerebrovascular diseases and other chronic diseases, measurements of cerebral blood flow by 133-xenon clearance method showed that an intracarotid injection of 1 microgram/kg of YC-93 increased cerebral blood flow by 28.8% without changing arterial blood pressure and arterial pCO2, and that an intravenous 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. Thus, YC-93 produced a potent cerebral vasodilation not only in experimental animals but also in human patients in the same dose, and seemed to act perhaps directly on the cerebral vascular beds.