Effects of Liver Damage and Nephrectomy on Anticonvulsant Activity of Mysoline and Phenobarbital

Mysoline and phenobarbital were tested after their oral administration in normal, liver-damaged, and nephrectomized rats for their ability to prevent the tonic extensor component of maximal electroshock seizures. The results were analyzed for the effect of these procedures on the intensity and the duration of anticonvulsant action of these compounds. Liver damage significantly increased the anticonvulsant activity and the duration of action of both drugs. Nephrectomy increased the anticonvulsant activity and the duration of action of Mysoline but not of phenobarbital. The results suggest that, in the rat, both the liver and the kidney are important for the degradation and elimination of Mysoline, whereas the liver is the principal organ for the degradation of phenobarbital into products devoid of anticonvulsant activity.