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Journal of Pharmacology And Experimental Therapeutics, Vol. 119, Issue 2, 255-262, 1957
Copyright © 1957 by American Society for Pharmacology and Experimental Therapeutics

CONVULSANT HYDRAZIDES I: IN VITRO AND IN VIVO INHIBITION OF VITAMIN B6 ENZYMES BY CONVULSANT HYDRAZIDES

K. F. Killam 1 and J. A. Bain 1

1 Department of Pharmacology, University of Illinois, School of Medicine, Chicago, Illinois

A comparison of free amino acids in brain extracts indicated that semicarbazide-induced seizures are associated with a decreased level of gamma-aminobutyric acid; pentylenetetrazol seizures were not accompanied by changes in amino acid levels.

Hydrazides have been shown equipotent in inhibiting in vitro three enzyme systems catalyzed by pyridoxal phosphate: l-cysteine desulfhydrase, glutamicaspartic transaminase and l-glutamic acid decarboxylase. Inhibition of the latter system was competitively reversed by pyridoxal phosphate. In contrast, pentylenetetrazol, strychnine and a convulsant barbiturate did not alter levels of enzyme activity.

In vitro synthesis of pyridoxal phosphate was not inhibited by administration of the convulsant agents.

Assay of the three pyridoxal phosphate enzyme systems in animals convulsed with hydrazides showed inhibition of only l-glutamic acid decarboxylase.

Submitted on August 16, 1956




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Copyright © 1957 by the American Society for Pharmacology and Experimental Therapeutics.