Relationship between gamma-aminobutyric acid metabolism and antivitamin B6-induced convulsions.
The correlation between the gamma-aminobutyric acid (GABA) metabolism and convulsions by some vitamin B6 antagonists, DL-penicillamine (PeA), hydrazine (Hyd), thiosemicarbazide (TSC) were investigated. Glutamic acid decarboxylase (GAD) and gamma-aminobutyric acid transaminase (GABA-T) activities were inhibited during convulsions by three antagonists, and GABA content was not changed by PeA, increased by Hyd and decreased by TSC in mice whole brain. In subcellular fractions of brain, GAD activity was inhibited and GABA content decreased in synaptosomes during convulsions by the above three drugs. Aminooxyacetic acid (AOAA), a potent GABA-elevating agent, showed an anticonvulsant property against convulsions by TSC for several hours after the injection of AOAA, but lost this property 16hr after treatment. During the convulsions by TSC 16hr after the AOAA-pretreatment, the GABA content in synaptosomes was less than that from the group treated with AOAA alone, though its GABA level was higher than the normal level. From the above results, the GABA content and GAD activity in synaptosomes might be deeply associated with convulsions by B6 antagonists.
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism; D000085:Acetates / Q000494:pharmacology*; D000625:Aminooxyacetic Acid / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006834:Hydrazines / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010396:Penicillamine / Q000494:pharmacology*; D011736:Pyridoxine / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D012663:Semicarbazides / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000085:Acetates; D006834:Hydrazines; D012663:Semicarbazides; D000625:Aminooxyacetic Acid; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase; D010396:Penicillamine; D011736:Pyridoxine