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

Ten patients with clinically definite multiple sclerosis (MS) and action tremor were treated with isoniazid (INH) in a double-blind single crossover trial. The daily dose of INH administered during the 4-week treatment phase of the trial was determined by acetylator phenotype with slow acetylators receiving 12 mg/kg per day and rapid acetylators 20 mg/kg per day. Six of eight patients who completed the trial showed clinical improvement in the postural (alternating) tremor while on INH but the degree was minimal in all cases. Results of tremograms indicated that improvement also occurred in the intentional (synchronous) component of three patients while on INH, but this did not achieve statistical significance. Cerebrospinal fluid (CSF) levels of gamma-aminobutyric acid (GABA) homocarnosine and ornithine were markedly elevated with INH therapy (providing evidence for substantial inhibition of GABA aminotransferase activity and increase in GABA in the CNS), but no correlation was found between the degree of GABA elevation in the CSF and the clinical response. Side effects were minimal and well tolerated. Although INH appears to have a limited therapeutic role, a trial is warranted in MS patients with postural tremor.
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PMID:A controlled trial of isoniazid therapy for action tremor in multiple sclerosis. 354 5

Intraperitoneal injection of ethanol (1-2 g/kg) and chlordiazepoxide (2-16 mg/kg) suppressed susceptibility to audiogenically induced, clonic-tonic seizures and antagonized forelimb tremor in rats undergoing ethanol withdrawal, 30 min after treatment. However, a smaller dose of ethanol (0.5 g/kg) actually increased clonic seizure frequency, suggesting that ethanol exerts a biphasic proconvulsant/anticonvulsant action. Direct activation of gamma-aminobutyric acid (GABA) receptors by intracisternal administration of GABA (100-1000 micrograms), muscimol (0.3-1.0 micrograms) or 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) (0.3-3.0 micrograms) 5 to 10 min before testing also reduced susceptibility to audiogenic clonic-tonic seizures. In sharp contrast to these anticonvulsant actions, GABA, muscimol and THIP had no effect on withdrawal-induced forelimb tremors. Blockade of GABA uptake with 1-2,4-diaminobutyric acid (300 and 600 mg/kg i.p.) and inhibition of GABA transaminase with aminooxyacetic acid (12.5 and 25.0 mg/kg i.p.) both reduced susceptibility to seizures. However, anticonvulsant doses of these two drugs, unlike GABA, muscimol and THIP, also reduced forelimb tremor. Three other GABA transaminase inhibitors, gamma-vinyl GABA (450 and 900 mg/kg i.p.), gamma-acetylenic GABA (50-150 mg/kg i.p.) and ethanolamine-O-sulfate (250-750 mg/kg i.p.), were inactive against ethanol withdrawal audiogenic seizures and forelimb tremors. These results indicate that direct GABA receptor activation can selectively suppress one type of ethanol withdrawal response (i.e., audiogenic seizure susceptibility) while failing to influence another (forelimb tremors).
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PMID:Differential sensitivity of ethanol withdrawal signs in the rat to gamma-aminobutyric acid (GABA)mimetics: blockade of audiogenic seizures but not forelimb tremors. 631 80