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)

K-opioid substances have been shown to stimulate and/or depress the HPA activity. The objective of this study was to determine the effects of the acute and chronic administration of U-50,488H, a k-opioid receptor agonist, on the pituitary-adrenocortical activity in the rat. The acute administration of U-50,488H (25 mg/kg i.p.) produced a hypothermic effect and an increase in plasma levels of B-END-LI and cortisol, effects which were prevented by naloxone (3 mg/kg s.c.). Chronic administration of U-50,488H twice a day for 4 days resulted in a decrease in basal plasma levels of B-END-LI and cortisol and in the development of tolerance to its neuroendocrine and hypothermic effects. In rats made tolerant to U-50,488H, naloxone precipitated hypothermia (which is an index of opiate dependence in rats), whereas no changes in plasma B-END-LI and cortisol levels were seen. These data suggest that k receptors may be involved in the regulation of pituitary-adrenocortical activity in physiological conditions and during opiate abuse. On the other hand, U-50,488H induced only negligible dependence in rats, which was not morphine-like.
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PMID:Pituitary-adrenocortical response to acute and chronic administration of U-50,488H in the rat. 166 98

A series of studies were conducted in order to further characterize the previously reported effect of morphine to diminish hepatocellular concentrations of glutathione (GSH) in mice. Naive ICR mice administered morphine (i.p.) in doses up to 1000 mg/kg had diminished hepatic GSH concentrations, with a maximum depletion of approximately 50% occurring at doses of 250 mg/kg or greater. No such effect from an acute challenge with morphine was observed in morphine-tolerant mice. The intracerebro-ventricular administration of the opioid receptor antagonist naltrexone (250 micrograms) completely blocked the hepatic GSH depression resulting from the systemic (i.p.) administration of morphine (100 mg/kg). When morphine (100 micrograms) was administered by the i.c.v. route, GSH concentrations in liver and plasma were significantly altered while heart and kidney were unchanged. Variable responses to i.c.v. morphine were obtained in spleen, stomach and lung. The depression of hepatic GSH was found not to be a consequence of morphine-induced hypoxia or hypothermia, and could not be attributed to intracellular oxidation of GSH.
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PMID:Perturbation of glutathione by a central action of morphine. 275 29

We investigated the effects of thiorphan, a selective inhibitor of endopeptidase 24.11 'enkephalinase', kelatorphan ((R)-3-(N-hydroxy-carboxamido-2-benzylpropanoyl)-L-alanine), and RB 38 A ((R)-3-(N-hydroxycarboxamido-2-benzylpropanoyl)-L-phenylalanine) two almost complete inhibitors of enkephalin metabolism, on the naloxone-precipitated morphine withdrawal syndrome in rats. Inhibitors administered intracerebroventricularly reduced several symptoms of the withdrawal syndrome. Jumping, chewing and tooth chattering were decreased by all drugs. The rise in plasma corticosterone and the hypothermia were reduced by kelatorphan and RB 38 A whereas rhinorrhea was blocked by thiorphan, tremor by kelatorphan and diarrhoea by RB 38 A. Other signs remained unchanged. These data suggest that an increase in opioid receptor occupancy by endogenous opioid peptides, protected from biotransformation specially by mixed inhibitors reduced the severity of the morphine abstinence symptoms in rats.
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PMID:Comparison of selective and complete inhibitors of enkephalin-degrading enzymes on morphine withdrawal syndrome. 277 28

In many cases, body temperature is altered in response to opioid agonists, but the direction, magnitude and time course of alteration vary with a number of factors. Body temperature may be subject to differential modification by different opioid receptor types. The authors examined the effect (i.c.v.) of the selective mu, delta and kappa opioid agonists, [D-Ala2, MePhe4, Gly5-ol] enkephalin (DAGO), [D-Pen2, D-Pen5] enkephalin and U50488H, respectively, on the body temperature of restrained and unrestrained rats. Each of the three opioid agonists produced a differentiable profile of body temperature changes. DAGO caused a primary decrease in body temperature of restrained rats and an increase in body temperature of unrestrained rats. The pretreatment dose of naloxone necessary to attenuate the hyperthermic response to DAGO of unrestrained rats was 10 times higher than that required to block the hypothermic response to DAGO in restrained rats. Low doses of both [D-Pen2, D-Pen5]enkephalin and U50488H caused a decrease in body temperature of both restrained and unrestrained rats. Hypothermic responses to U50488H were not blocked by naloxone, whereas hypothermic responses to [D-Pen2, D-Pen5]enkephalin in unrestrained rats were potentiated by naloxone. The results indicate that the three compounds modified body temperature by different means, suggesting activation of different opioid, and perhaps nonopioid, receptors. This may reflect a differential modulation of body temperature by endogenous opioids depending on the specific peptide released and the receptor type activated. Besides the physiologic implications, body temperature responses provided a sensitive pharmacologic measure for distinguishing the in vivo activity of different selective opioid agonists.
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PMID:Body temperature response profiles for selective mu, delta and kappa opioid agonists in restrained and unrestrained rats. 283 73

Pretreatment of rats with the irreversible mu-opioid receptor antagonist, beta-funaltrexamine (beta-FNA), 20-40 mg kg-1 s.c., produced a dose-related antagonism of the reduction in respiratory rate, gastrointestinal (GI) propulsion, rotarod reaction latencies and body temperature produced by morphine administration 24 h later, suggesting that these effects are mediated via mu-opioid receptors. The kappa-receptor agonist, U-50,488H, was without effect on respiratory rate at the doses tested, but produced hypothermia, sedation and low maximum inhibition of GI propulsion. These effects of U-50,488H were not blocked by beta-FNA suggesting that they are mediated via kappa-receptors.
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PMID:Effect of beta-funaltrexamine on opioid side-effects produced by morphine and U-50, 488H. 286 74

The ability of the selective cyclic mu-opioid receptor antagonist, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), to inhibit the acute and chronic effects of morphine in vivo was studied in mice. Intracerebroventricular (i.c.v.) administration of CTOP antagonized the analgesic effect of morphine in a dose-dependent manner, as measured by the heat-irradiant (tail-flick) method. CTOP was more effective than naloxone in inhibiting analgesia on a molar basis. CTOP also antagonized the acute morphine-induced hypermotility. CTOP caused withdrawal hypothermia and a loss of body weight in morphine-dependent animals. After the development of morphine-induced chronic dependence, CTOP administered i.c.v. caused a dose-dependent loss of body weight and hypothermia, and was about 10-400 times more potent than naloxone. CTOP administered alone to drugnaive mice did not cause antinociception, changes in body weight or body temperature.
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PMID:Central effects of the potent and highly selective mu opioid antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) in mice. 290 58

Morphine-induced analgesia, and the development of morphine-induced tolerance and dependence was determined in mice which had drunk caffeinated water (1 mg/ml) for 14 days or in mice which had received (-)-N6-(phenylisopropyl)-adenosine (PIA) 1 mg/kg i.p. for 14 days. Analgesia was assessed by the tail flick assay. The development of dependence was assessed by determining the ED50 of naloxone to precipitate withdrawal jumping (3 h after 100 mg/kg morphine pretreatment or 72 h after s.c. implantation of a morphine 75 mg pellet) and by determining the extent of naloxone-precipitated hypothermia in morphine-implanted animals. In mice chronically administered caffeine, the ED50 for morphine-induced analgesia was significantly decreased while the naloxone ED50 for withdrawal jumping increased by 2-fold after both types of morphine pretreatment. In control animals (tap water for 14 days), doses of 1 and 10 mg/kg of naloxone caused significant hypothermia in morphine-implanted animals. Doses of naloxone up to 100 mg/kg did not cause significant hypothermia in morphine-implanted animals which had received chronic caffeine. The development of tolerance was determined by computing the morphine potency ratio for the tail flick assay (tolerant ED50/control ED50). In mice chronically administered caffeine, the potency ratio was decreased significantly in morphine-implanted animals when compared to control. Morphine-induced analgesia, tolerance and dependence was not changed significantly in animals chronically administered PIA. Neither the distribution of morphine to the brain nor the opioid receptor binding parameters for [3H]etorphine and [3H]naltrexone were altered in mice chronically administered caffeine or PIA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of chronic administration of caffeine on morphine-induced analgesia, tolerance and dependence in mice. 300

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

The prototype sigma opioid receptor agonist N-allyl-normetazocine (SKF 10,047) was injected into the third cerebral ventricle of conscious, unrestrained cats, and their temperature was monitored automatically from the retroperitoneal space. In a cold environment (0 degrees C) a small, but not dose-related, hypothermia occurred after doses of 100-500 micrograms. This response was not antagonized by naloxone given intraventricularly either 15 min before or 1 hr after the opioid. A smaller hypothermia resulted after 250 micrograms SKF 10,047 when the environmental temperature was 22 degrees C, whereas hyperthermia developed in a hot environment (34 degrees C). Thus SKF 10,047 appears to allow body temperature to drift, upward in the heat and downward in the cold, a pattern indicative of thermoregulatory depression. These results are similar to those obtained in the first 2-3 hr after pentazocine administration, and they support a previous classification of the initial temperature response to centrally injected pentazocine as due to stimulation of sigma opioid receptors.
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PMID:Central injection of a sigma opioid receptor agonist alters body temperature of cats. 626 55

Phencyclidine elicits hyperthermia at low doses and hypothermia at high doses in rats. Naloxone antagonizes both effects. Phencyclidine's effects on thermo-regulation are probably mediated by an interaction with a mu opiate receptor.
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PMID:Naloxone antagonism of the thermoregulatory effects of phencyclidine. 628 81


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