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 hypothermic effects of intraperitoneal (IP) administration of the full benzodiazepine agonist loprazolam (1, 10 mg/kg); the partial agonist Ro 17-1812 (1, 10 mg/kg); the benzodiazepine receptor antagonist flumazenil (10, 20 mg/kg); the benzodiazepine inverse agonists Ro 15-4513 (1, 3, 10 mg/kg) and Ro 19-4603 (0.03, 0.1, 0.3 mg/kg) and the beta-carboline inverse agonists FG 7142 (10, 30 mg/kg) and DMCM (1, 3, 10 mg/kg) were investigated in three strains of mice. TO mice were less sensitive than CBA/cA and DBA/2 mice, since only loprazolam and the partial and full beta-carboline inverse agonists FG 7142 and DMCM lowered body temperature in these animals. CBA/cA mice were particularly sensitive to the hypothermic effects of loprazolam and Ro 17-1812, and also responded to the beta-carboline but not the benzo diazepine inverse agonists. In contrast, DBA/2 mice responded with moderate hypothermia to loprazolam, Ro 17-1812, and to the partial inverse agonist Ro 15-4513, and exhibited marked hypothermia in response to the more efficacious benzodiazepine inverse agonist Ro 19-4603 and to FG 7142 and DMCM. Flumazenil did not alter body temperature. DBA/2 mice were also more sensitive to the convulsant activity of inverse agonists than TO mice. CBA/cA mice exhibited enhanced sensitivity to the convulsant, but not the hypothermic, effects of Ro 19-4603, showing dissociation of these responses. The mechanisms underlying the genetic differences in sensitivity of mice to the hypothermic and convulsant action of the different ligands are unknown and warrant further investigation.
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PMID:Strain differences in sensitivity to the hypothermic effects of benzodiazepine receptor ligands in mice. 136 36

The possible involvement of tumor necrosis factor-alpha (TNF) in the metabolic disturbances induced by anti-CD3 monoclonal antibodies (mAb) was analyzed in DBA/2 mice injected with 50 micrograms of the anti-murine CD3 mAb 145-2C11. First, we found that 145-2C11 induces a profound hypothermia maximal between 3 h and 6 h after the injection (at 3 h: -3.0 +/- 0.1 degrees C) as well as hypoglycemia (blood glucose levels at 6 h and 24 h: 76 +/- 13 mg/100 ml and 92 +/- 22 mg/100 ml, respectively, p less than 0.001 as compared with control values). These metabolic changes are preceded by the release of TNF into the circulation (peak serum TNF levels at 2 h: 50 +/- 23 pg/ml, p less than 0.01 as compared with controls). The release of TNF induced by 145-2C11 depends on the effect of the mAb on T cells as it is not observed in athymic nude mice while lipopolysaccharide-resistant C3H/HeJ mice also display a significant rise in serum TNF (peak levels at 2 h: 59 +/- 44 pg/ml). Pretreatment of DBA/2 mice with 12 mg of rabbit anti-murine TNF antibodies completely prevents the hypothermia while the hypoglycemia is significantly attenuated. Finally, F(ab')2 fragments of 145-2C11 induce only a transient hypoglycemia (blood glucose levels at 6 h: 109 +/- 14, p less than 0.001 as compared with controls) but neither hypothermia nor significant TNF release. We conclude that TNF is a major mediator of the acute metabolic changes induced by the intact form of 145-2C11.
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PMID:Hypothermia and hypoglycemia induced by anti-CD3 monoclonal antibody in mice: role of tumor necrosis factor. 213 64

When given a two-bottle choice between gradually increasing morphine concentrations (in 0.2% saccharin) and plain tap water, C57BL/6J mice consumed almost 90% of their daily fluid intake from the morphine-saccharin bottle, while the DBA/2J strain, in contrast, consumed 13% or less from the morphine-saccharin solution. The C57BL/6J strain consistently consumed mean daily doses of morphine sulfate in excess of 200 mg/kg, which was sufficient to induce an easily discernable withdrawal syndrome upon removal of the morphine solution, either with or without naloxone challenge. Hypothermia, tremor, wet dog shakes, jumping, and diarrhea were prominent withdrawal signs. In separate experiments, the saccharin was removed from the morphine-containing bottle, yet the C57BL/6J mice continued to prefer the morphine solution over tap water. In complete contrast to the above, mice of the DBA/2J strain rejected the morphine-saccharin solution at the lowest concentration employed, and at no time did their mean daily morphine dose exceed 20 mg/kg. Thus, morphine-saccharin preference is strongly genetically determined, and a high degree of physical dependence can result in the morphine-preferring strain. Palatability differences appear not to be the predominant explanation for these differences in morphine-saccharin consumption.
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PMID:Physical dependence induced by the voluntary consumption of morphine in inbred mice. 232 Jun 38

The pattern of sensitivity of mice from three inbred strains were compared on measures of morphine-induced analgesia (hot plate), locomotor activity, hypothermia, Straub tail (muscular rigidity), antidiuresis and constipation. The DBA/2J strain emerged as the most sensitive strain for analgesia, retention of a water load (antidiuresis) and hypothermia. In addition, the DBA/2J mice had lower concentrations of morphine in the brain 30 min after injection and had the lowest Kd and the highest Bmax for naloxone as measured by in vitro receptor binding. In contrast, mice of the C57BL/6J strain were most sensitive when locomotor activity, Straub tail and constipation were measured. The C3H/HeJ mice were generally intermediate in their sensitivity to morphine. The observed strain differences indicate a rather high degree of genetic control for most of the effects studied, however, the low consistency of rank order among the three strains across these measures suggests that the genetically determined mechanisms are largely different between these measures of morphine sensitivity.
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PMID:Genetic dissociation of multiple morphine effects among C57BL/6J, DBA/2J and C3H/HeJ inbred mouse strains. 281 56

The influence of four centrally-acting alpha-1 adrenoceptor agonists, namely, 2(2-chloro-5-trifluoromethylphenylimino) imidazolidine (St 587), cirazoline, (-) 1,2,3,4-tetrahydro-8-methoxy-5-methylthio-2-naphthalenamine ((-)SKF 89748A) and 2-(2-methylindazol-4-imino)imidazolidine (Sgd 101/75) on the pharmacological effects of ethanol was investigated. All four drugs reduced the duration of ethanol-induced hypnosis in C57B1/6 mice, this effect being proportional to their relative potencies to exert central alpha-1 agonism. In prazosin-pretreated mice, St 587 failed to reduce the hypnotic effect of ethanol, which provided strong evidence for the role of alpha-1 agonism for the hypnosis reducing effect of St 587. Hyperactivity induced in C57B1/6 mice by a subhypnotic dose of ethanol and St 587 was reported earlier. In the present study, St 587, cirazoline and (-)SKF 89748A produced similar response, but no correlation between this effect and ethanol hypnosis blockade could be established. Interestingly, this hyperactivity response was not exhibited by Swiss-Webster, BALB/c or DBA-2 mice--strains in which St 587 exerted little or no antagonism to ethanol-induced hypnosis. Of the alpha-1 agonists, only St 587 reduced the ethanol-induced hypothermia in C57B1/6 mice. St 587 also blocked this effect of ethanol in BALB/c mice in which this drug failed to reduce the ethanol-induced hypnosis. It was concluded that ethanol-induced hypothermia and hypnosis are not interrelated. None of the alpha-1 agonists modified the pentobarbitone-induced hypnosis or the rate of elimination of ethanol in C57B1/6 mice. In this strain, the reduction of the duration of ethanol-induced hypnosis by the alpha-1 agonists is a selective and centrally-mediated response.
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PMID:Modification of certain pharmacological effects of ethanol by lipophilic alpha-1 adrenergic agonists. 288 99

Effects of morphine on the rectal temperature and respiratory rate, and [3H]naloxone binding to brain membranes from seven brain regions were compared among six strains of male mice, including DBA/2N, C57BL/6N, BALB/c, C3H/HeN, A/J and ICR. The administration of 10 and 20 mg/kg doses of morphine HCl to these strains of mice decreased rectal temperature and respiratory rate. However, there was a significant strain difference in these two measures of the effect of morphine. The DBA/2N strain was the most sensitive in both measures of morphine action. The magnitude of hypothermia was positively correlated with respiratory depression among six strains of mice after the administration of 10 and 20 mg/kg morphine HCl, suggesting common mechanisms. Strain difference in naloxone binding in the brain regions could not explain that of the morphine responses, because there was no correlation between the intensity of morphine-induced hypothermia or respiratory depression and the regional [3H]naloxone binding for the mouse strains.
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PMID:Strain difference in the effects of morphine on the rectal temperature and respiratory rate in male mice. 309 May 93

3,7-Dimethyl-1-propargylxanthine (DMPX), a caffeine analog that exhibits in vitro selectivity for A2-adenosine receptors, compared to A1-adenosine receptors, has now been investigated with respect to in vivo potency and selectivity. DMPX potently and selectively blocked the actions of the potent A2 adenosine agonist, 5'-N-ethylcarboxamidoadenosine (NECA), in DBA/2 mice, compared to blockade of the same responses elicited by the selective A1-adenosine agonist, N6-cyclohexyladenosine (CHA). DMPX was 57-fold more potent versus NECA-induced hypothermia than versus CHA-induced hypothermia and 11-fold more potent versus NECA-induced behavioral depression than versus CHA-induced behavioral depression. The hypothermia is mediated by peripheral receptors, based on blockade by 8-(p-sulfophenyl)theophylline (PSPT), while the behavioral depression is centrally mediated, based on lack of blockade by PSPT. DMPX was 28- and 15-fold more potent than caffeine in blocking peripheral and central NECA-responses, respectively. DMPX was equipotent with caffeine versus CHA-induced hypothermia and 2.5-fold more potent than caffeine versus CHA-induced behavioral depression. The motor stimulating potency of DMPX (ED50 10 mumol/kg) was slightly greater than caffeine.
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PMID:3,7-Dimethyl-1-propargylxanthine: a potent and selective in vivo antagonist of adenosine analogs. 319 54

The present study investigated the importance of body temperature during intoxication in mediating differences between five inbred strains of mice (C57BL/6J; BALB/cJ; DBA/2J; A/HeJ; 129/J) in their acute sensitivity to the hypnotic effects of ethanol. Mice exposed to 22 degrees C after ethanol injection became hypothermic and exhibited statistically significant differences between strains in rectal temperatures at the return of the righting reflex (RORR), duration of loss of the righting reflex (LORR), and blood and brain ethanol concentrations at RORR. Exposure to 34 degrees C after injection offset ethanol-hypothermia and markedly reduced strain-related differences in rectal temperatures and blood and brain ethanol concentrations at RORR. Brain ethanol concentrations at RORR were significantly lower in C57, BALB, DBA and A/He mice exposed to 34 degrees C compared to mice exposed to 22 degrees C during intoxication suggesting that offsetting hypothermia increased ethanol sensitivity in these strains. Taken with previous in vitro studies, these results suggest that genetically determined differences in acute sensitivity to the behavioral effects of ethanol reflect differences in body temperature during intoxication as well as differences in sensitivity to the initial actions of ethanol at the cellular level.
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PMID:Genetically determined differences in ethanol sensitivity influenced by body temperature during intoxication. 321 Aug 97

Subcutaneous administration of the enkephalin analogue FK33-824 (FK) elicited a dose-related decrease in rectal temperature and respiratory rate in male ddY strain mice. Naloxone and 3 days' implantation of morphine pellet decreased the effects of FK, suggesting the involvement of opioid receptors and cross-tolerance with morphine to both effects of FK. A positive correlation was found between the FK-induced decrease in rectal temperature and that in respiratory rate among the 6 strains of inbred mice including BALB/c, C3H, A/J, CBA, C57BL/6 and DBA/2. The degree of hypothermia elicited by FK was different among strains, whereas marginal strain difference was seen in the respiratory depression induced by FK. The strain difference in the FK responses may be due to the difference in the opioid receptor subtypes in the brain.
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PMID:Effects of the enkephalin analogue FK33-824 on rectal temperature and respiratory rate in male mice. 322 53

Amfonelic acid (AFA), a non-amphetamine central stimulant dose-dependently reduced the hypnotic effect of ethanol in C57B1/6 mice. It did not enhance the elimination of ethanol. Amfonelic acid failed to modify the duration of pentobarbitone-induced hypnosis or the ethanol-induced hypothermia in these animals. Combined treatment with amfonelic acid and a lipophilic alpha 1-adrenoceptor agonist was not more effective than amfonelic acid alone in blocking ethanol hypnosis. The stimulation of locomotor activity by amfonelic acid in C57B1/6 mice was more sensitive to the blocking effect of ethanol than stimulation induced by d-amphetamine. The blocking effect of amfonelic acid, but not that of d-amphetamine, on the effects of ethanol developed tolerance. In pimozide-pretreated mice, amfonelic acid failed to reduce the ethanol-induced hypnosis. Hence it appears that dopamine (DA) released by amfonelic acid is responsible for its antagonism of ethanol. However, though amfonelic acid acted as a strong releaser of DA in Swiss-Webster, CD-1, DBA-2 and BALB/c mice, in these strains it failed to reduce the effect of ethanol. Moreover, methylphenidate, a dopaminergic stimulant, which acts by a mechanism similar to that of amfonelic acid was not effective in reducing the hypnotic effect of ethanol in C57B1/6 mice. For these reasons, additional mechanisms may have to be considered to explain this strain-dependent effect of amfonelic acid.
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PMID:Studies on the interaction between ethanol and amfonelic acid. 358 33


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