Temperature dependence of the toxic effects of phenytoin on peripheral neuromuscular function of the rat tail

We studied the acute effects of a single dose of phenytoin (250 mg/kg) on peripheral neuromuscular function. The evoked muscle action potentials of the dorsal segmental muscles in the rat tail, and the conduction velocity of the dorsal nerve trunk which innervates them, were measured before and after the intraperitoneal injection of phenytoin. The experiments were performed at different temperatures, 27 (physiological tail temperature), 36 and 37°C (physiological central temperature) in different groups of animals. The amplitudes of the evoked muscle action potentials in the treated groups showed no significant modifications at 27°C, at 36°C a small nonsignificant decrease could be observed, and a complete block occurred at 37°C. The mean blocking time was approximately one hour. No significant variations of conduction velocity were observed at 27 and 36°C, whereas it decreased significantly after 30 minutes at 37°C. The results presented confirm phenytoin toxicity. How far these results, especially the decrease of nerve conduction velocity observed at 37°C, confirm a previous hypothesis which supported that peripheral and central nervous system are affected by phenytoin by similar mechanisms, is discussed.