JPET

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Maynert, E. W.
Right arrow Articles by Kaji, H. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Maynert, E. W.
Right arrow Articles by Kaji, H. K.
Journal of Pharmacology And Experimental Therapeutics, Vol. 137, Issue 1, 114-121, 1962
Copyright © 1962 by American Society for Pharmacology and Experimental Therapeutics

ON THE RELATIONSHIP OF BRAIN ggr-AMINOBUTYRIC ACID TO CONVULSIONS

E. W. Maynert 1 and Hideko K. Kaji 1

1 The Johns Hopkins University School of Medicine, Baltimore, Maryland

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.

Submitted on January 8, 1962




This article has been cited by other articles:


Home page
 J. Neurophysiol.Home page
Y. De Koninck and I. Mody
Endogenous GABA Activates Small-Conductance K+ Channels Underlying Slow IPSCs in Rat Hippocampal Neurons
J Neurophysiol, April 1, 1997; 77(4): 2202 - 2208.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
K Gale and M. Iadarola
Seizure protection and increased nerve-terminal GABA: delayed effects of GABA transaminase inhibition
Science, April 18, 1980; 208(4441): 288 - 291.
[Abstract] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1962 by the American Society for Pharmacology and Experimental Therapeutics.