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Research ArticleArticle

ON THE RELATIONSHIP OF BRAIN γ-AMINOBUTYRIC ACID TO CONVULSIONS

E. W. Maynert and Hideko K. Kaji
Journal of Pharmacology and Experimental Therapeutics July 1962, 137 (1) 114-121;
E. W. Maynert
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Hideko K. Kaji
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Abstract

Mice injected with thiosemicarbazide and sacrificed during a tonic extensor seizure showed a significantly smaller decrease in brain GABA than was found in animals similarly treated with semicarbazide, acetone semicarbazone, thiocarbohydrazide, isonicotinic acid hydrazide or 3-deoxypyridoxine phosphate.

Compared with the hydrazides, methylhydrazine and 1-phenyl-2-hydrazinopropane caused little change in GABA in mice. A convulsant dose of hydrazine caused an increase in brain GABA.

Large doses of succinonitrile and diphenylhydantoin were almost as effective as the hydrazides in lowering GABA. Metrazole, picrotoxin and insulin caused smaller but significant decreases. Reserpine had no effect.

A number of different treatments were explored in an attempt to elevate brain GABA in mice and rats, but success was achieved only with hydrazine and with hydroxylamine. Hydrazine was much the more satisfactory drug in that it caused larger increases in GABA and was less toxic.

In doses sufficient to elevate brain GABA in rats, neither hydrazine nor hydroxylamine altered the incidence or duration of electrically-induced clonic seizures or modified the pattern of a maximal seizure. Hydrazine also failed to confer protection against pentylenetetrazol seizures in mice.

Hydrazine-treated mice injected with semicarbazide exhibited maximal seizures at supranormal concentrations of brain GABA.

It was concluded that hydrazide-induced convulsions are not directly related to the total concentration of GABA in whole brain. The possibilities that the delay in the onset of hydrazide convulsions may represent a slow entry of the drugs into brain and that convulsions may cause a supranormal utilization of GABA for energy-yielding reactions of the brain were considered in the discussion.

Footnotes

    • Received January 8, 1962.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 137, Issue 1
1 Jul 1962
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Research ArticleArticle

ON THE RELATIONSHIP OF BRAIN γ-AMINOBUTYRIC ACID TO CONVULSIONS

E. W. Maynert and Hideko K. Kaji
Journal of Pharmacology and Experimental Therapeutics July 1, 1962, 137 (1) 114-121;

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Research ArticleArticle

ON THE RELATIONSHIP OF BRAIN γ-AMINOBUTYRIC ACID TO CONVULSIONS

E. W. Maynert and Hideko K. Kaji
Journal of Pharmacology and Experimental Therapeutics July 1, 1962, 137 (1) 114-121;
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