ACTION OF DIPHENYLOXAZOLIDINEDIONE ON BRAIN RESPIRATION AT VARIED TEMPERATURE LEVELS

¹ Department of Physiology, Stanford University

1. Procedures were described whereby constant rates of oxygen consumption were obtained with cerebral cortex slices for periods exceeding three hours.

2. The effect of intravenous injection of graded doses of 5,5-diphenyl-2,4-oxazolidinedione (DPO) in minimal volume, to a small group of rats was reported for the dosage range of 20 to 100 mgm. per kgm.

3. A concentration-action curve was presented which illustrates the effect of graded concentrations of DPO on the oxygen consumption of rat cerebral cortex slices. This was compared with the concentration-action curve of the related substituted oxazolidinedione, propazone. With rising concentration of DPO there was first a moderate augmentation, then a profound inhibition of brain respiration. The augmentation phase did not occur with propazone. Furthermore there was more rapid development of inhibition and a greater maximum inhibitory effect with DPO than with propazone.

4. It was found that DPO had some specificity in respect of its inhibitory action on brain respiration. Like propazone and like various narcotics, DPO decreased the oxygen consumption of cerebral cortex slices much more markedly in the presence of glucose than in the presence of succinate.

5. Under the conditions of these experiments the inhibition of brain respiration by DPO was not reversible, whereas the inhibition by propazone was in large part reversible.

6. Inhibition of brain respiration by DPO became relatively less marked with decrease in temperature. Thus at 37.5°C. only 10% of the respiration was stable toward DPO, while at 15°C. this fraction was 36%.