GABA metabolism

Sodium valproate GM PM 6 also 1 Inhibition of GABA metabolism... 

Introduced initially for absence seizures, this drug is now known to be effective in and used to treat tonic lonic seizures and most types of epilepsy. It was found to inhibit GABA transaminase and so elevate GABA concentrations and inhibition. This is achieved, however, over a slower time-course than its anti-seizure effect, especially experimentally, which is now thought to be due to its phenytoin-like, use-dependent block of sodium channels. Since, unlike phenytoin, the full effect of valproate takes some weeks to develop, its slower effect on GABA metabolism and activity should not be ignored. 

Tiagabine blocks neuronal uptake of GABA and has reported benefits in panic disorder and PTSD (Lydiard 2003). Topiramate has complex actions on GABA and glutamate and was found to be helpful for some symptoms of PTSD (Berlant and van Kammen 2002). Vigabatrin inhibits GABA metabolism and has been shown to block induced panic attacks in healthy volunteers (Zwanzger et al. 2001). 

Gibson KM, Jakobs C, Pearl PL, Snead OC (2005) Murine succinate semialdehyde dehydrogenase deficiency, a heritable disorder of GABA metabolism with epileptic phenotype. IUBMB Life 57 639-644... 

Jakobs C, Jaeken J, Gibson KM (1993) Inherited disorders of GABA metabolism. J Inherit Metab Dis 16 704-715... 

Page MG, Ankoma-Sey V, Coulson WF, and Bender DA (1989) Brain glutamate and gamma-aminobutyrate (GABA) metabolism in thiamin-deficient rats. British Journal of Nutrition 62, 245-53. 

The following experiment was carried out to determine to what extent GABA-T can be inhibited in vivo after administration of inhibitors shown to be active in vitro. The rationale for such an approach assumes that GABA-T is, quantitatively, the most important enzyme in GABA metabolism. Thus, in the following scheme, administration of a GABA-T inhibitor will prevent the oxidation of GABA to CO2. 

Sadasivudu B, Murthy RK. 1978. Effects of ammonia on monoamine oxidase and enzymes of gaba metabolism in mouse brain. Arch Int Physiol Biochim 86 67-82. 

Some recent observations have underlined the necessity of interpreting with caution the results of experiments which have sought to modify GABA metabolism. Animals habituated to, and then withdrawn from, barbiturate drugs, develop (as do human beings) spontaneous convulsions or an increased susceptibility to audiogenic seizures . It was shown by Essig that these... 

Hedgecock, E. (1976) GABA metabolism in Caenorhabditis elegans. PhD thesis. University of California, Santa Cruz. 

No. Gabapentin does not interact with GABA receptors, nor does it interfere with GABA metabolism. 

Another putative antiseizure action of valproic acid involves GABA metabolism. In vitro, valproic acid stimulates the activity of glutamic acid decarboxylase, the GABA synthetic enzyme, and inhibits GABA degradative enzymes. 

Carbamazepine s mechanism of action is similar to that of phenytoin, blocking sodium ion channels. Ethosuximide blocks calcium channels benzodiazepines and barbiturates facilitate the inhibitory actions of GABA topiramate may block glutamate receptors and vigabatrin inhibits GABA metabolism. The answer is (A). 

Adminstration of AOAA (50 mg/kg) 1 h before decapitation increases the postmortal rise in GABA by as much as 50% (Yamatsu et al., 1982). There are substantial regional variations from no effect of AOAA on the increase of GABA postmortem in substantia nigra and frontal cortex, to large effects in hippocampus and superior colliculus. Therefore, GABA metabolism does not seem to be completely or immediately inhibited by anoxia. 

Baxter C F (1976) Some Recent Advances in Studies of GABA Metabolism and Compartmentation, in GABA in Nervous System Function (Roberts E, Chase T N, and Bower D.B. eds ), Raven Press, New York... 

Jung M. J, Lippert B., Metcalf B. W., Bohlen P., and Schlechter P J (1977a) y-Vinyl-GABA (4-aminohexionic acid), a new selective irreversible inhibitor of GABA-T Effects on brain GABA metabolism in mice. /. Neurochem 29, 797-802... 

Metcalf B W (1979) Inhibitors of GABA metabolism Biochem Pharmacol 28, 170 1712. 

Walters J R., Eng N, Pericic D, and Miller L. P (1978) Effects of aminooxyacetic acid and L-glutamic acid-7-hydrazide on GABA metabolism in specific brain regions. / Neurochem 30, 759-766... 

---