Effect of L-cycloserine on brain GABA metabolism

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Abstract
Administration of L-cycloserine to mice resulted in a dramatic decrease in activities of 4-aminobutyrate:2-oxoglutarate aminotransferase (GABA-T, EC-2.6.1.9) and L-alanine:2-oxoglutarate aminotransferase (ALA-T, EC-2.6.1.2) in brain and liver. L-Aspartate:2-oxoglutarate aminotransferase was inhibited only slightly, and brain glutamic acid decarboxylase not at all. Liver ALA-T activity returned to near normal levels within 24 h of L-cycloserine administration, whereas liver GABA-T and brain ALA-T activities had returned only halfway to normal levels in the same period. Recovery in the activity of brain GABA-T was even slower. A consequence of inhibition of brain GABA-T activity was an elevation in GABA content of the tissue which was maximal 3 h after L-cycloserine administration and which was still noticeable 8 h after the drug treatment. L-Cycloserine was a potent in vitro inhibitor of brain GABA-T activity. Inhibition was competitive with respect to GABA, the Ki value being 3.1 .times. 10-5 M. Prior administration of L-cycloserine to mice significantly delayed onset of isonicotinic acid hydrazide induced convulsions.