Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The anticonvulsant, adverse and biochemical effects of the novel antiepileptic drug vigabatrin (gamma-vinyl GABA), which increases GABA (gamma-aminobutyric acid) levels by inhibition of the GABA degrading enzyme GABA aminotransferase, were examined in amygdala-kindled rats after acute and chronic administration. Vigabatrin proved to be a potent anticonvulsant drug at acute doses (100-200 mg/kg), but during chronic administration, the anticonvulsant activity of the treatment was lost already in the second week of treatment. Tolerance also developed to the adverse effects, i.e. hypothermia, sedation and motor impairment. Determination of vigabatrin in plasma indicated that tolerance was not due to declining drug levels. Furthermore, determination of endogenous amino acids in plasma showed that GABA levels were highly elevated throughout the period of treatment, although the extent of GABA accumulation decreased in the second week. After cessation of chronic treatment with vigabatrin, there was no clear indication of withdrawal symptoms, except a prolonged seizure or afterdischarge duration in experiments with 100 mg/kg per day. The data suggest that chronic treatment with vigabatrin may be associated with a loss of anticonvulsant efficacy, at least when the drug is given as monotherapy.
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PMID:Development of tolerance to the anticonvulsant effect of vigabatrin in amygdala-kindled rats. 161 78

GABAergic drugs can positively or negatively influence recovery of neurobehavioral function following brain injury. Direct potentiation of GABA-mediated inhibition at the post-synaptic receptor (i.e., via GABA, muscimol, diazepam, phenobarbital) after brain damage has been associated with impaired functional recovery. What remains unclear, however, is whether the mechanism of action by which GABA is augmented contributes to a drug's impact on the recovery process. Vigabatrin, a novel anti-convulsant that inhibits GABA-transaminase, was administered chronically after unilateral anteromedial cortex lesions and recovery from somatosensory deficits assessed. In contrast to the direct GABA receptor agonists, vigabatrin did not adversely impact (i.e., was neutral) recovery from neurobehavioral deficits at any of the anti-convulsant doses tested. Measurable secondary drug effects like sedation and hypothermia diminished over time and were reversible upon drug discontinuation. These results suggest that the degree to which a GABAergic agent impacts the recovery process after brain injury is dependent on the drug's mechanism of action.
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PMID:Impact of the novel anti-convulsant vigabatrin on functional recovery following brain lesion. 1267 Dec 69

Vigabatrin is a GABA derivative (gamma-vinyl GABA) which inhibits irreversibly the enzyme activity of GABA transaminase and thus increased indirectly brain GABA concentrations. We have used body temperature assay to examine the effects of Vigabatrin on thermoregulation in intact rats. In order to understand the mechanism of thermoregulatory action of Vigabatrin at cellular level, we have investigated its effect on individual warm-sensitive preoptic area/anterior hypothalamus (PO/AH) neurons in rat brain slice preparations. The results of the present study suggest that Vigabatrin produced dose-dependent hypothermia in rats and also increased temperature sensitivity of warm-sensitive PO/AH neurons.
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PMID:Effects of GABA-transaminase inhibitor Vigabatrin on thermoregulation in rats. 2087 40