Superior protective effects of phenytoin against hypoxia in a pharmacological screening test

The selection of drugs to prevent the development of pathology in cerebral infarction remains an important problem. For the selection of effective drugs from among a large number of possible candidates, widely-used test screening techniques are sufficient for obtaining a good understanding of candidate drug effects. The effects of various drugs on the survival time of mice made hypoxic by exposure to a 4% O2-96% N2 gas have been examined. The survival time of 110 control animals was 170 +/- 6 s, showing a nearly normal distribution pattern. No control mouse had a survival time beyond 8 min. The survival time after the drugs were administered was as follows: suloctidil (12.5 mg/kg, n = 11), 1833 +/- 487 s; vitamin E (200 mg/kg, n = 15), 1160 +/- 342 s; pentobarbital (50 mg/kg, n = 12), 602 +/- 74 s; and phenytoin (100 mg/kg, n = 10), 2667 +/- 452 s. In contrast, administration of vitamin C, coenzyme Q, cytochrome c, beta-methasone, mannitol or germanium-132 did not result in prolongation of survival time. Comparison of the percentage of animals in each group which survived for more than 1 h showed 0% in the control group, 45.5% in the suloctidil group (12.5 mg/kg), 23.5% in the vitamin E group (200 mg/kg), 0% in the pentobarbital group (50 mg/kg) and 70% in the phenytoin group (100 mg/kg). These findings suggest that phenytoin is the most effective drug in combatting the effects of hypoxia (survival time was expressed as mean +/- SE).