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

Morphine produced a hypothermic effect in restrained rats which was antagonized by naloxone. This effect was completely inhibited by gamma-acetylenic-GABA, an inhibitor of GABA transaminase and by baclofen, a specific GABAB agonist. Pretreatment with diazepam, an agonist of the benzodiazepine receptor, partially inhibited morphine-induced hypothermia. Flumazenil, a benzodiazepine receptor blocker, potentiated the action of morphine on body temperature. A role of brain GABA in the thermoregulatory effects of morphine is proposed on the basis of these results.
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PMID:GABAergic mechanisms in morphine-induced hypothermia. 207 23

Acute exposure of adult male albino rats (110-120 g) to higher environmental temperature (40 +/- 1 degrees C) increased body temperature (BT). This increase of BT was also dependent on the duration of exposure. Treatment with muscimol (1 mg/kg, i.p.), a GABA agonist, produced hypothermia at room temperature (28 +/- 1 degree C) and resistance to increase the body temperature when exposed to higher temperature (40 +/- 1 degree C). Administration of bicuculline (1 mg/kg, i.p.), a GABA antagonist, on the other hand, enhanced BT more than that observed in control (normal) rat exposed to higher temperature (40 +/- 1 degree C), although at room temperature bicuculline treatment did not show any effect on BT. Pretreatment with ethanolamine-O-sulfate (EOS) (2 g/kg, s.c.), a GABA transaminase inhibitor, to rats exposed to higher temperature increased BT as in control (normal) rat. Inhibition of central GAD activity with mercaptopropionic acid (MPA) (70 mg/kg, i.p.) produced resistance to increase BT during its period of action when rats were exposed to higher environmental temperature (28 +/- 1 degree C). These results thus suggest that central inhibitory neuron, GABA, plays a regulatory role in thermoregulation.
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PMID:Involvement of GABA in environmental temperature-induced change in body temperature. 323 43

Some synthetic taurine analogues, namely ethanolamine-O-sulphate (EOS), N,N-dimethyltaurine (DMT), N,N,N-trimethyltaurine (TMT) and 2-aminoethylphosphonic acid (AEP) were shown to interact with rabbit brain GABA(A)- or GABA(B)-receptors, while (+/-)piperidine-3-sulfonic acid (PSA) inhibited the activity of rabbit brain 4-aminobutyrate transaminase. This suggests that they behave like direct/indirect GABA agonists or GABA antagonists and affect thermoregulation and gross motor behaviour (GMB) which are under GABA control. In the present study micromole (1.2-48) amounts of these compounds were i.c.v. injected in conscious, restrained rabbits while monitoring rectal temperature (RT), ear skin temperature (EST) and GMB. AEP, EOS, DMT and TMT induced a dose-related hyperthermia, ear vasoconstriction and excitation of GMB, while PSA induced a dose-related hypothermia, ear vasodilation and inhibition of GMB. EOS antagonized in a dose-related fashion hypothermia induced by 60 nmol THIP, a GABA(A) agonist, while AEP, DMT and TMT counteracted that induced by 8 nmol R(-)Baclofen, a GABA(B) agonist. In conclusion, EOS and AEP, DMT, TMT seem to act as GABA(A) and GABA(B) antagonists, respectively, while PSA behaves like an indirect GABA agonist, all affecting the central mechanisms which drive rabbit thermoregulation.
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PMID:GABA-mediated effects of some taurine derivatives injected i.c.v. on rabbit rectal temperature and gross motor behavior. 1658 17

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