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)

Tyrosine hydroxylase (TH) levels in the rat neostriatum are decreased by chronic treatment with methamphetamine. GABAergic neurons could potentially interact with the nigrostriatal dopaminergic neurons in either the neostriatum or the substantia nigra; therefore, the GABA transaminase inhibitors, amino-oxyacetic acid, gamma-acetylenic GABA and ethanolamine-O-sulfate, were evaluated for possible influences on the methamphetamine-induced decrease in TH. TH was measured by the procedure of Nagatsu et al. (1964). Methamphetamine (10 mg/kg, s.c.) was given every 6 h for 24 h. Thirty-six h after initiation of the methamphetamine treatment, neostriatal TH activity was approximately 70% of control. Concurrent administration of amino-oxyacetic acid (20 mg/kg, i.p.) or gamma-acetylenic GABA (15 mg/kg, i.p.) with methamphetamine completely blocked the TH depression. Dose-response curves were constructed for amino-oxyacetic acid and gamma-acetylenic GABA. A single intraventricular injection of ethanolamine-O-sulfate (400 micrograms/rat), 2-6 h before initiating the methamphetamine regimen, also completely blocked the TH depression. These data suggest that the striatonigral or other GABAergic systems are involved in the regulation of the functional state of the nigrostriatal dopaminergic neurons, and that enhanced GABAergic function will antagonize the effects of high doses of methamphetamine.
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PMID:Blockade of methamphetamine-induced depression of tyrosine hydroxylase by GABA transaminase inhibitors. 610 24

Gamma-vinyl-gamma-aminobutyric acid (GVG) elevates central nervous system gamma-aminobutyric acid (GABA) levels by irreversibly inhibiting GABA transaminase. An open-label clinical trial in humans suggested that GVG may reduce cocaine and methamphetamine use. To test safety and to obtain preliminary data on efficacy of GVG for treating methamphetamine dependence, we conducted a double-blind, placebo-controlled, parallel group study of GVG interaction with the cardiovascular and subjective effects produced by methamphetamine. Non-treatment seeking methamphetamine-dependent volunteers received either GVG (N=8) or placebo (N=9) by random assignment. GVG treatment was initiated at 1 g/day and increased to 5 g/day. After reaching the target dose of 5 g/day, participants received methamphetamine (15+30 mg, IV), and cardiovascular and subjective effects were assessed. No serious adverse events were noted, and the total number of adverse events was similar between the treatment groups. Considering the full time course and peak effects independently, no significant differences were detected between the groups for systolic or diastolic blood pressures, or heart rate, following methamphetamine exposure. Some methamphetamine-induced cardiovascular changes approached significance (p<0.10) and may warrant attention in future trials. Methamphetamine-induced subjective effects ("any drug effect", "high", "crave methamphetamine") were statistically similar between GVG and placebo treatment groups. Pharmacokinetic data indicate that GVG treatment did not alter methamphetamine or amphetamine plasma levels, and there was no association between methamphetamine or amphetamine plasma levels and peak cardiovascular effects. Taken together, the data indicate that GVG treatment is generally well tolerated but not efficacious in attenuating the positive subjective effects of methamphetamine in the laboratory.
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PMID:The cardiovascular and subjective effects of methamphetamine combined with gamma-vinyl-gamma-aminobutyric acid (GVG) in non-treatment seeking methamphetamine-dependent volunteers. 1969 34