Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P80404 (GABA transaminase)
 786 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Gamma-vinyl GABA (GVG) is a new anticonvulsant drug that enhances levels of GABA in the brain by irreversibly inhibiting GABA transaminase. 2. To further evaluate the effects and mechanism of action of GVG in the human brain, we measured acetylcholinesterase (AChE) activity and levels of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), cyclic nucleotides (cAMP, cGMP), total GABA (TGABA), and GVG in CSF of 78 patients with complex partial epilepsy. The CSF samples were taken at baseline and after 3 months of GVG administration (3 g GVG per day). Thereafter, the responders (= 50% decrease in number of seizures) were divided (double-blind) into two groups that received either 1.5 g or 3 g of GVG per day for the next 3 months. The third CSF sample was taken after this double-blind period. 3. TGABA levels were increased during the GVG treatment (p less than 0.001). In the whole group of patients AChE, HVA, 5-HIAA, and cAMP did not differ from baseline values, cGMP levels were slightly elevated after 3 months of GVG administration (p = 0.019), but were no longer elevated after 6 months. Responders had slightly lower AChE activity than nonresponders (p = 0.041). After 6 months of drug treatment the cGMP levels of patients receiving 1.5 g of GVG did not differ from those receiving 3 g. 4. In conclusion, GVG administration elevates levels of TGABA in the CSF without any clear of constant change to cholinergic and aminergic transmission or effect on cyclic nucleotides. Our study further emphasizes the specific mechanism of action of GVG via GABAergic transmission.
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PMID:Effect of gamma-vinyl GABA treatment on cholinergic and aminergic neurotransmission and on cyclic nucleotides in human complex partial epilepsy--a CSF study. 245 56

L-Cycloserine dose-dependently inhibited the activity of gamma-aminobutyric acid (GABA)-transaminase (GABA-T) and elevated the level of GABA in whole mouse brain with a peak effect 3-4 hr after a single intraperitoneal injection. At a dose (30 mg/kg) which elevated the level of GABA almost 4-fold, L-cycloserine moderately increased the content of alanine and slightly reduced that of aspartate, glutamate and glycine in the brain. L-Cycloserine (10-30 mg/kg, p.o. or i.p.) prevented tonic seizures induced by 3-mercaptopropionic acid (3-MPA) and audiogenic seizures in DBA/2 mice, without affecting those evoked by pentylenetetrazol, bicuculline and electroshock. Similarly small doses of L-cycloserine reduced the level of cGMP in the cerebellum of rats, prevented its elevation by 3-MPA and attenuated the hypothalamically-elicited rage reaction in cats. Larger doses of L-cycloserine (greater than 30-100 mg/kg) impaired the performance of mice in the rotarod, chimney and horizontal wire tests, and reduced spontaneous locomotor activity of rats. Upon repeated administration the inhibitory effect of L-cycloserine on the activity of GABA-T and on seizures elicited by 3-MPA in mice increased. In contrast, the depressant action of L-cycloserine on motor performance and locomotion declined in subchronically-treated mice and rats. The levels of amino acids in brain after repeated administration did not differ markedly from those in acutely-treated mice. It is suggested that small doses of L-cycloserine, probably by increasing GABAergic inhibition, reduce hyperexcitability in the brain in acute- and subchronically-treated animals. Larger doses of L-cycloserine, possibly by inducing multiple neurochemical changes, evoke central depressant effects which diminish during subchronic treatment.
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PMID:L-cycloserine: behavioural and biochemical effects after single and repeated administration to mice, rats and cats. 301 1