A correlation between changes in gamma-aminobutyric acid metabolism and seizures induced by antivitamin B6.
The effects of DL-penicillamine (DL-PeA), hydrazine and toxopyrimidine (TXP, 2-methyl-6-amino-5-hydroxymethylpyrimidine) on gamma-aminobutyric acid (GABA) metabolism in mouse brain were studied. All these compounds inhibited the activity of glutamate decarboxylase [EC 4.1.1.15] (GAD) and slightly inhibited that of 4-aminobutyrate: 2-oxoglutarate aminotransferase [EC 2.6.1.19] (GABA-T). In contrast, very different effects were observed on GABA levels; hydrazine caused a marked increase, DL-PeA had no effect, and TXP caused a slight decrease in the content of the amino acid. These results could be described by an equation which related the excitable state to changes in the flux of the GABA bypass. Since the values obtained from the equation clearly reflect the seizure activity, it is suggested that the decreased GABA flux might be a cause of convulsions induced by these drugs.
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors; D000613:Aminobutyrates / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000037:antagonists & inhibitors; D006834:Hydrazines / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010396:Penicillamine / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000613:Aminobutyrates; D006834:Hydrazines; D011743:Pyrimidines; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase; D010396:Penicillamine