Independent and combined effects of L-arginine and diazepam on ammonium chloride-induced convulsions in rats.
The independent and combined effects of L-arginine (840 mg/kg) and diazepam (0.75 mg/kg) pretreatment (30 min) were tested on ammonium chloride (400 mg/kg)-induced convulsions in rats. Ammonia concentrations were determined in blood and brain regions (cerebral cortex, brain stem and cerebellum) 30 min after L-arginine or diazepam treatment. Ammonia concentrations were measured at the time of induction of convulsions by ammonium chloride in L-arginine, diazepam or saline pretreated animals. L-arginine and not diazepam decreased ammonia concentrations in control as well as in ammonium chloride-treated animals. However, both the compounds suppressed convulsions elicited by ammonium chloride. Protection produced concurrently by these agents was much greater than that produced by them independently. It is concluded that convulsions caused by hyperammonemic condition can be suppressed either by preventing a rise in brain ammonia to toxic level or by anticonvulsant agents having a GABA potentiating action. A much greater protection can be achieved if agents having these properties are administered concurrently.
Paul
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Department of Pharmacology & Environmental Toxicology, Dr. A.L.M. Postgraduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai.
Jayakumar
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AR
D000641:Ammonia / Q000097:blood*; D000643:Ammonium Chloride; D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001120:Arginine / Q000627:therapeutic use*; D003975:Diazepam / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*
D000927:Anticonvulsants; D000643:Ammonium Chloride; D000641:Ammonia; D001120:Arginine; D003975:Diazepam