Anticonvulsant properties of amino-oxyacetic acid

Abstract

Amino-oxyacetic acid (AOAA), a compound which inhibits γ-aminobutyric-α-ketoglutaric transaminase in vitro and causes accumulations of γ-aminobutyric acid (GABA) in vivo, has anticonvulsant activity against convulsions caused by thiosemicarbazide in rats, mice, and cats and against methionine sulfoximine convulsions in cats. Pentobarbital sodium and trimethadione were slightly active in protecting against thiosemicarbazide-induced convulsions whereas chlorpromazine and methadone were inactive. Pyridoxal, ethanol (in fasted rats), and paraldehyde showed anticonvulsant activity in thiosemicarbazide convulsions. The anticonvulsant activity of AOAA did not appear to be due to increased GABA levels in the brain for the following reasons: a) maximum GABA levels occurred 6–8 hr after administration of AOAA. Optimal protection against thiosemicarbazide, however, was afforded during the first 3 hr after administration and it had fallen off markedly at 6 hr. b) Hydroxylamine, which has been reported to raise GABA levels, had no anticonvulsant activity on thiosemicarbazide.