Abstract
The anticonvulsant ED50 of 5,5βdiphenylβ2,4βoxazolidinedione (DPO) was determined in male CF#1 mice by a standard maximal electroshock method, and compared with that for phenytoin (PHT) and phenobarbital (PB). Acute neurotoxicity (TD50) and acute lethality (LD50) were also determined. These parameters are reported with respect to i.p. dosage, and blood and brain concentrations. The anticonvulsant ED50 (308 mg/kg) of DPO was significantly less than that of either PHT (7.1 mg/kg) or PB (19.0 mg/kg). The same order of potency was observed when expressed in terms of blood or brain concentrations, although important quantitative differences were noted. Neurotoxicity was observed with doses of DPO required for anticonvulsant action (TD50 = 335 mg/kg). Furthermore, acute lethality (LD 50 = 373 mg/kg) was observed at doses not significantly different (Pβ₯.05) than the ED50. Doses between the ED50 and LD50 produced profound motor incoordination, seizures, and coma. Because of its extremely narrow margin of safety, DPO would not be considered a likely candidate for evaluation as a therapeutic agent in man. However, a greater understanding of its pharmacology is desirable because, in spite of its structural similarity to PHT, it contrasts sharply in certain properties.