Acute effects of phenytoin on peripheral nerve function in the rat

The acute effect of intraperitoneal injection of phenytoin on rat peripheral nerve was studied. Conduction velocities in the ventral caudal nerve were measured hourly and phenytoin blood levels were obtained 4 to 5 hours after injection. Conduction velocity decreased by 23% in the 25 phenytoin-treated animals from a control value of 30.0 plus or minus 1.3m/sec (mean plus or minus SEM) to a 4-hour value of 23.0 plus or minus 1.3 m/sec (P less than 0.001). The phenytoin blood level 4 hours after injection was 45.0 plus or minus 1.3 micrograms/ml. Amplitudes of evoked muscle action potentials in the treated group decreased by 37% from control values. High levels of phenytoin induce prompt slowing of nerve conduction velocity within hours, which may be mediated by mechanisms similar to those responsible for toxic central effects.