Effects of phenytoin on the cyclic nucleotide system in the motor nerve terminal.

The effects of phenytoin on the motor nerve terminal were evaluated on the in vivo cat soleus nerve muscle preparation. Phenytoin, 10 mg/kg, reduced the repetitive aftercharges in motor nerve endings due to tetanic conditioning. It also reduced the repetitive activity due to adenylate cyclase activation with NaF, or to exogeneous dibutyryl cyclic AMP. These effects of phenytoin could be reversed by administering theophylline, a phosphodiesterase inhibitor, or by increasing the extracellular concentration of calcium. The effects of phenytoin could also be reversed by 3-aminopyridine, but not by tetraethylammonium chloride. Verapamil, a calcium current antagonist, produced effects that were identical to phenytoin. It is concluded that phenytoin blocks a cyclic nucleotide-mediated calcium influx that is associated with transmitter release. This calcium flux also appears to control a slow potassium current that is responsible for post-tetanic hyperpolarization.