Evidence for an involvement of the ammonia-decreasing action of L-arginine in suppressing picrotoxin-induced convulsions in rats and its additive action with diazepam.

The effects of pre- (30 min before challenge) and post-treatment (5 min after challenge) of L-arginine (840 mg kg(-1)) were tested on picrotoxin-induced increase in ammonia concentrations in brain regions (cerebral cortex, brain stem and cerebellum) and the accompanying convulsive responses in adult male rats. The effect of pre- and post-treatment of L-arginine was tested on the action of diazepam against picrotoxin-induced convulsions. Picrotoxin-induced increase in ammonia concentrations in the brain regions was reverted partially by L-arginine pre-treatment. However, L-arginine pre-treatment failed to inhibit convulsions independently and concurrently with diazepam. On the other hand, L-arginine post-treatment reverted ammonia to control level in all brain regions. A partial but significant inhibition of convulsions was found in these animals. The effect produced concurrently by L-arginine and diazepam post-treatment was much greater than that produced by these agents independently. These results suggest that brain ammonia has a partial but significant participation in the convulsant action of picrotoxin. L-arginine has produced a partial protection of picrotoxin-induced convulsions by reverting brain ammonia to control level. The data further suggest that the duration of action of L-arginine is considerably short and that L-arginine has an additive anticonvulsant action with diazepam.