Ammonia toxicity: comparative protective effect of various arginine and ornithine derivatives, aspartate, benzoate, and carbamyl glutamate

Metab Brain Dis. 1986 Mar;1(1):25-35. doi: 10.1007/BF00998474.


Ornithine and arginine compounds were highly effective in preventing an increase in blood ammonia and in preventing or minimizing encephalopathy after acute subcoma, coma-inducing, or lethal doses of NH4+. Similar protection was seen after subacute loading with glycine. Ornithine ketoacid derivatives were no more effective than ornithine alone or ornithine glutamate. Ornithine appeared to be a little more effective than arginine, but the differences were slight. Aspartate and glutamate alone were ineffective. Carbamyl glutamate was much less effective than either ornithine glutamate or arginine glutamate. Orotic acid excretion was markedly increased in the presence of excess NH4+. This increment was eliminated with ornithine or arginine, although the reduction with arginine was unpredictably erratic. Aspartate increased the orotic acid excretion and the amount of urea formed. Sodium benzoate was borderline in its effect on the blood ammonia and on orotic acid excretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ammonia / metabolism
  • Ammonia / toxicity*
  • Ammonium Chloride
  • Animals
  • Arginine / therapeutic use*
  • Aspartic Acid / therapeutic use*
  • Benzoates / therapeutic use*
  • Brain Diseases / drug therapy*
  • Brain Diseases / metabolism
  • Coma / chemically induced
  • Coma / metabolism
  • Dose-Response Relationship, Drug
  • Glutamates / therapeutic use*
  • Male
  • Rats
  • Rats, Inbred Strains


  • Benzoates
  • Glutamates
  • Ammonium Chloride
  • N-carbamylglutamate
  • Aspartic Acid
  • Ammonia
  • Arginine