The mechanism of action of a novel cerebral protective drug against anoxia I. The effect on cerebral energy demand.

The effect of a novel cerebral protective drug, Y-9179, on cerebral metabolic rate was investigated in mice in comparison with that of phenobarbital. Injection of 150 mg/kg of phenobarbital to adult mice resulted in the decrease in the rates of use of phosphocreatine, ATP, glucose and glycogen in brain, and the cerebral metabolic rate was estimated to be 12.8 mumoles/g/min in terms of the use-rate of high energy phosphate equivalents (approximately P). This value corresponded to 43% of that of the control animals. In the adult animals treated with 1 mg/kg of Y-9179, the rates of use of the energy reserves were decreased, and the cerebral metabolic rate was determined to be 19.6 mumoles/g/min. A similar result was obtained in the experiments with 9-day old mice; the cerebral metabolic rate was decreased from 4.82 to 2.65 mumoles/g/min by the treatment with Y-9179. Furthermore, the Y-9179-treated mice had less lactate accumulation and higher energy reserves than the control animals. Barbiturate and Y-9179 proved to have common properties, namely, the cerebral protection against anoxia and the lowering action of cerebral metabolic rate. These findings suggest that the mechanism by which Y-9179 protects against cerebral anoxia is mediated by the lowering of cerebral energy demand.