Protection by phenytoin and calcium channel blocking agents against the toxicity of diisopropylfluorophosphate.

Pretreatment of male Swiss-Webster mice with phenytoin, 25 mg/kg, verapamil, 25 to 3.0 mg/kg, nifedipine, 0.05 to 0.1 mg/kg, nitrendipine, 0.1 mg/kg, and nimodipine, 1 to 2.5 mg/kg, elevated the LD50 of diisopropylfluorophosphate (DFP) to a significant degree. In addition, these agents enhanced the protection that can be obtained from atropine and 2-pralidoxime. The protective effects of phenytoin cannot be attributed to an anticonvulsant action, per se, since carbamazepine, phenobarbital, and diphenylbarbituric acid in anticonvulsant doses did not influence DFP lethality. The mechanism of action of phenytoin and the other effective calcium channel blockers in providing protection over and above that achieved with atropine and 2-pralidoxime appears to be due to a protective action of the former agents on central respiratory centers and peripheral nicotinic sites and may involve the movement of calcium into excitable membranes.