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.
Vanaja
P
P
Department of Pharmacology and Environmental Toxicology, Dr A.L.M. Postgraduate Institute of Basic Medical Sciences, University of Madras, Chennai, India.
Jayakumar
A R
AR
D000641:Ammonia / Q000097:blood*; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D003975:Diazepam / Q000494:pharmacology*; D004347:Drug Interactions / Q000502:physiology; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology*; D022124:Hyperammonemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000641:Ammonia; D001120:Arginine; D003975:Diazepam; D018756:GABA Antagonists; D018757:GABA Modulators; D010852:Picrotoxin; D005680:gamma-Aminobutyric Acid