Action of 5,5-diethyl-1,3-oxazine-2,4-dione (dioxone) on respiration and circulation

The action of 5,5-diethyl-1,3-oxazine-2,4-dione (dioxone) has been studied in rats, rabbits, cats and dogs. Dioxone produced a marked stimulation of respiration in anaesthetized, decerebrate and spinal animals when given in doses that did not induce convulsions. This effect was generally accompanied by a rise in blood pressure, which was more marked in cats than in dogs and rabbits. Dioxone antagonized the respiratory and circulatory depression due to pentobarbitone. The respiratory stimulating effect of dioxone appears to be 2 or 3 times greater than that of leptazol, and comparable to that of megimide. Like leptazol, nikethamide and megimide, dioxone has no direct effect on cardiac function. Dioxone did not elicit respiratory and blood pressure changes when allowed to come in contact with the carotid sinus receptors. Dioxone enhanced the reflex excitability of bulbar centres, as demonstrated by the increase in respiratory response either to temporary common carotid artery occlusion in dogs or to electrical stimulation of the central cut end of Hering's nerve in the cat. Dioxone also reduced the inhibition of respiration induced by electrical stimulation of the central cut end of the vagus nerve. Whether this central action of dioxone is direct or not cannot at present be elucidated, though a section at intercollicular level did not prevent the respiratory stimulation produced by this substance.