EFFECTS OF DIPHENYLHYDANTOIN ON THE DURATION OF RESPIRATORY ACTIVITY DURING ANOXIA

¹ Department of Pharmacology, Emory University, Atlanta, Georgia

Diphenylhydantoin prolonged the duration of respiratory activity in cats and guinea pigs subjected to nitrogen anoxia as well as in the decapitated guinea-pig head. Trimethadione lacked this effect. This effect of diphenylhydantoin was not due to an action on carotid or aortic chemoreceptors, nor was it related to drug-induced hypothermia or diminished convulsive activity. Midcollicular decerebration greatly increased the respiratory survival time of cats during anoxia, and diphenylhydantoin caused no further increase in these preparations. Electroencephalographic studies revealed no qualitative difference between control and diphenylhydantoin-treated animals during anoxia.

Treatment with reserpine did not decrease the effectiveness of diphenylhydantoin in prolonging survival time. However, a dose of 75 mg/kg iodoacetate prevented the increase in survival time with diphenylhydantoin without affecting control survival values. A decrease in the frequency of respiration during anoxia as compared with control frequencies was found to accompany the prolongation of survival time with diphenylhydantoin in the guinea pig. It is suggested that the action of diphenylhydantoin in prolonging respiratory survival time during anoxia may be due in part to a direct effect on the respiratory neurons of the central nervous system.