Elimination of Metrazol

Abstract

Pharmacological and clinical evidence points to the fact that metrazol is very rapidly detoxicated in the body. The intravenous administration of a convulsive dose produces typical clonic convulsions from which the animal rapidly recovers. There is a possibility that the metrazol might be excreted by the kidneys, and so our first step consisted in eliminating this possibility. Chemical analysis of the urine of cats receiving convulsive doses of metrazol snowed none of the drug to be present in the urine. Bilaterally nephrectomized cats showed the same reaction to a convulsive dose of metrazol as they did before the performance of the nephrectomy. Hinsberg has shown that practically no metrazol is excreted by the intestinal route. It therefore seems logical that metrazol is not excreted but is detoxified. The liver has generally been assumed to be the locale for drug detoxication. We therefore administered phosphorus to cats. Cats treated in this way died from the administration of a dose of metrazol which formerly produced only slight convulsions. The role of the liver was further tested by a comparison of the dose required to produce convulsions when the drug was infused into the marginal ear vein or the portal vein of rabbits. In all cases a larger amount was required to produce convulsions when administered by the portal route. This evidence seems to establish the fact that metrazol is detoxified rather than excreted and that the liver plays an important role in the detoxication process.