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)

1. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) dose-dependently induced hypothermia in mice. 2. The 5-HT1A receptor partial agonists, buspirone, gepirone and ipsapirone, also dose-dependently induced hypothermia. 3. The 8-OH-DPAT temperature response was antagonized by the 5-HT1 receptor antagonists quipazine (2 mg kg-1, i.p.), (+/-)-propranolol (10 mg kg-1, i.p.). (+/-)-pindolol (5 mg kg-1, i.p.), spiroxatrine (0.5 mg kg-1, i.p.) and metitepine (0.05 mg kg-1, i.p.), but not by 5-HT2 (ketanserin) or 5-HT3 (MDL 72222, GR 38032F) receptor antagonists. 4. The response was also antagonized by the dopamine D2 receptor antagonists, haloperidol and BRL 34778. No other catecholamine or muscarinic receptors were involved in mediating the response. 5. Destruction of 5-hydroxytryptamine (5-HT)-containing neurones with the neurotoxin, 5,7-dihydroxytryptamine (75 micrograms, i.c.v.), abolished the response to 8-OH-DPAT indicating that the 5-HT1A receptors involved were located on 5-HT neurones. 6. Chronic antidepressant treatment down-regulated this 8-OH-DPAT response. In addition, chronic administration of anxiolytics and neuroleptics was also effective in this respect. Down-regulation was also observed following repeated administration of 8-OH-DPAT (0.5 mg kg-1, s.c.), (+/-)-pindolol (10 mg kg-1, i.p.) and ketanserin (0.5 mg kg-1, i.p.). 7. In conclusion, these data confirm that 8-OH-DPAT-induced hypothermia is mediated by 5-HT1A autoreceptors. They also indicate that the response involves D2 receptors.The present study also shows that a wide range of antidepressant drugs down-regulate this response although this property is not restricted to antidepressant treatments. Therefore, care should be exercised when interpreting data from this paradigm.
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PMID:Characterization of 8-OH-DPAT-induced hypothermia in mice as a 5-HT1A autoreceptor response and its evaluation as a model to selectively identify antidepressants. 142 68

The potency and efficacy of the selective dopamine D2 receptor agonist quinpirole, the mixed D1/D2 agonist apomorphine, and the selective D1 receptor agonist SKF 38393 in producing hypothermia and changes in locomotor activity were evaluated in four strains of mice: CBA/J, C57BL/6J, ICR Swiss and CF1. CBA/J mice previously have been shown to be deficient in dopamine cell and receptor number relative to other strains such as C57BL/6J mice, whereas ICR Swiss and CF1 are commonly used strains of mice. Quinpirole (0.125 to 1.0 mg/kg) was equiefficacious and equipotent in producing hypothermia in all 4 strains. Apomorphine (0.125 to 16 mg/kg) was equiefficacious in producing hypothermia in all 4 strains, but was approximately four-fold less potent in CBA/J mice than in the other strains. SKF 38393 had little effect on body temperature in any of the 4 strains. Basal motor activity was lowest in CBA/J mice, and tended to be highest in ICR Swiss mice. Quinpirole (0.125 to 32 mg/kg) had no effect on motor activity in CBA/J mice, but decreased motor activity in the other 3 strains. Apomorphine (1 to 16 mg/kg) produced modest increases in motor activity in all 4 strains. The magnitude of the changes produced by apomorphine was comparable in all strains when expressed as change from mean control values. SKF 38393 (8 to 64 mg/kg) also increased motor activity in all 4 strains, with comparable increases when expressed as change from mean control values. The present results are consistent with the interpretation that inherited deficiencies in dopamine cell and receptor number in CBA/J mice produce functional decrements in D2, but not D1, dopamine receptor function.
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PMID:Potency and efficacy of dopamine agonists in mouse strains differing in dopamine cell and receptor number. 168 81

The ability of neuroleptics to induce dopamine D2 receptor supersensitivity has been linked to the onset of tardive dyskinesia, the major side-effect of these drugs. Brain iron metabolism has been shown to be involved in the regulation of dopamine D2 receptors. We now examined the effect of chronic treatment with FeCl2 on chlorpromazine-induced D2 receptor supersensitivity. The results show that FeCl2 (5 mg/kg per day for 21 days) given to rats treated with chlorpromazine (10 mg/kg per day, for 21 days) prevented the onset of supersensitive biochemical and behavioral (apomorphine) expressions of DA D2 receptor. Inclusion of iron did not affect the chlorpromazine-induced sedation or hypothermia. Moreover, the combined chronic iron-chlorpromazine treatment produced the same net effects as chronic chlorpromazine on striatal amounts of dopamine, DOPAC (dihydroxyphenylacetic acid) and HVA (homovanillic acid). Chlorpromazine medication caused a decrease in liver non-haem iron levels (40%) but not in brain iron. The effect of the neuroleptic drug on iron stores and the involvement of iron in the neuroleptic-induced dopamine supersensitivity suggest that mobilization of iron from the periphery into the brain may play an important role in the mechanism of action of the neuroleptics.
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PMID:Prevention of neuroleptic-induced dopamine D2 receptor supersensitivity by chronic iron salt treatment. 168 31

A new benzamide, cis-N-(1-benzyl-2-methylpyrrolidin - 3 - yl) - 5 - chloro - 2 - methoxy - 4 - methylaminobenzamide (YM-09151-2) exhibited more potent and longer-lasting inhibitory effects on apomorphine-induced behaviours (stereotyped behaviour, emesis and hypothermia), and methamphetamine-induced stereotyped behaviour, conditioned avoidance response and open field behaviour, conditioned avoidance response and open field behaviour than either structurally similar benzamides (YM-0850 and sulpiride) or classical neuroleptics [chlorpromazine (CPZ) and haloperidol(HPD)]. Such inhibitory effects of YM-09151-2 relative to cataleptogenicity were greater than those of CPz and HPD. In contrast, sulpiride elicited few of the neuroleptic effects described above. YM-09151-2, a potent inhibitor for dopamine-sensitive adenylate cyclase (Ki: 3.0 nM) reduced, in a selective manner, the binding of [3H]dopamine to the dopamine D1 receptor (Ki:4.8 nm) associated with adenylate cyclase rather than to the dopamine D2 receptor (Ki: 0.98 microM) independent of adenylate cyclase. Sulpiride, on the contrary, inhibited only the binding to the dopamine D2 receptor, CPZ and HPD antagonized [3H]dopamine nonselectively at the two distinct dopaminergic receptors. These results suggest that YM-09151-2 is a potent and long-lasting neuroleptic with a highly selective blocking action on the dopamine D1 receptor.
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PMID:Neuroleptic properties of cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylaminobenzamide (YM-09151-2) with selective antidopaminergic activity. 611 70

Benzocycloalkyl and benzocycloalkenyl moities linked, directly or via an alkyl chain, to oxygen-bearing heteroarylpiperazines were synthesized, in an attempt to obtain potent and selective antagonists at postsynaptic 5-HT1A receptors. From the numerous arylpiperazines described in the literature, 1-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazine (3a) was chosen as a model of an arylpiperazine in view of its selectivity for 5-HT1A receptors versus alpha 1-, alpha 2-, and beta-adrenergic receptors, as well as dopamine D1 and D2 receptors. Two other closely-related arylpiperazines, 1-(1,5-benzodioxepin-6-yl)piperazine (3b) and 1-(benzofuran-7-yl)piperazine (3c), were also examined in this study. All compounds showed high affinity at 5-HT1A sites (8.10 < or = pKis < or = 9.35), and the majority behaved as antagonists in vivo in blocking the hypothermia induced by the 5-HT1A agonist 8-OH-DPAT in the absence of a marked effect alone at equivalent doses. An in vivo evaluation of dopamine D2 receptor antagonist properties revealed that the majority of compounds was devoid of activity at this site, in marked contrast to BMY 7378 which displayed virtually no selectivity for 5-HT1A versus dopamine D2 receptors. Moreover, six compounds of the present series, 8, 10, 11, 14, 25, and 37, showed > 10-fold selectivity in vitro for 5-HT1A versus alpha 1-adrenergic receptors. Compound 14 displayed an optimal compromise between potency (pKi = 8.75), marked antagonist activity, and selectivity toward alpha 1-adrenergic (81-fold) and dopamine D2 (195-fold) receptors. These characteristics clearly distinguish 14 from previously-reported ligands such as the postsynaptic 5-HT1A antagonist BMY 7378 and the weak partial agonist NAN 190 which, in contrast to the compounds of this series, belong to the well-exemplified class of imido derivatives of (o-methoxyphenyl)piperazines. The availability of 14 (S 15535) should facilitate the further elucidation of the functional role and potential therapeutic significance of 5-HT1A receptors.
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PMID:Characterization of potent and selective antagonists at postsynaptic 5-HT1A receptors in a series of N4-substituted arylpiperazines. 756 40

Clozapine (7.5-30.0 mumol kg-1 s.c.) produced a decrease in core temperature in the rat. The temperature decrease caused by clozapine (7.5 mumol kg-1 s.c.) was fully antagonized by the selective dopamine D1 receptor antagonist SCH 23390 (0.3 mumol kg-1) s.c.) and a partial antagonism was obtained by the selective dopamine D2 receptor antagonist raclopride (1.6 mumol kg-1 s.c.). On the other hand, the hypothermia was not antagonized by alpha-adrenoceptor antagonists (idazoxan and prazosin), 5-HT receptor antagonists ((-)-pindolol and ritanserin) or by the muscarinic M1 receptor antagonist scopolamine. The hyperthermia produced by the 5-HT1C/2 receptor agonist DOI (0.75 mumol kg-1) was blocked by clozapine (3.0 mumol kg-1 s.c.). Clozapine did not antagonize hypothermia produced by selective dopamine D1 and D2 receptor agonists (A 68930 and quinpirole), the alpha 2-adrenoceptor agonist clonidine, the 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) or the muscarinic M1 receptor agonist oxotremorine. The present results suggest that clozapine may be a partial agonist at brain dopamine D1 receptors.
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PMID:Antagonism by SCH 23390 of clozapine-induced hypothermia in the rat. 791 99

In rats kept at an ambient temperature of 22 degrees C, centrally and peripherally administered sauvagine induces a dose-dependent hypothermia. To clarify the regulatory mechanisms and to ascertain which neurotransmitter systems mediate sauvagine-induced hypothermia, we administered sauvagine intracerebroventricularly and subcutaneously in rats pretreated with antagonists of muscarinic receptors (atropine), opiate receptors (naloxone), alpha-adrenoceptors (phentolamine, yohimbine and prazosin), beta-adrenoceptors (propranolol) and dopamine receptors (haloperidol and spiperone). Systemic pretreatment of rats with atropine, naloxone, prazosin and propranolol left sauvagine-induced hypothermia unaltered. Pretreatment with phentolamine (4 mg/kg, s.c.), a non-selective alpha-adrenoceptor antagonist, and yohimbine (3 mg/kg, s.c.), a selective alpha 2-adrenoceptor antagonist, enhanced the hypothermic action of sauvagine. Pretreatment with haloperidol (2 mg/kg, s.c.), a non-selective dopamine receptor antagonist, and spiperone (80 micrograms/kg, s.c.), a selective dopamine D2 receptor antagonist, significantly reduced the temperature fall induced by centrally (4 micrograms/rat) and peripherally (20 micrograms/kg) administered sauvagine. Thus, sauvagine-induced hypothermia appears not to be mediated by interactions with cholinergic, endogenous opiate or noradrenergic systems, but rather D2 dopaminergic pathways alone are involved in the inhibitory effect of sauvagine on body temperature in the rat.
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PMID:Sauvagine-induced hypothermia: evidence for an interaction with the dopaminergic system. 791 1

In the present work, the effects of neurotransmitter antagonists on theophylline-induced changes in body temperature were investigated. Intraperitoneal (i.p.) administration of a low dose of theophylline (25 mg/kg) induced slight hyperthermia, while high doses (75 and 100 mg/kg) induced hypothermia. The hypothermic effect of theophylline was decreased by pretreatment of animals with the dopamine D2 receptor antagonists sulpiride (15 and 30 mg/kg i.p.) and pimozide (0.125 and 0.25 mg/kg i.p.), the muscarinic receptor antagonist atropine (2.5 and 5 mg/kg i.p.) and the 5-HT receptor antagonist metergoline (0.25 mg/kg i.p.). However, the dopamine D1 receptor antagonist SCH 23390 (0.05 and 0.5 mg/kg i.p.), the alpha-adrenoceptor antagonist phenoxybenzamine (2.5 and 5 mg/kg i.p.) and the beta-adrenoceptor antagonist propranolol (5 and 10 mg/kg i.p.) did not after the theophylline response. In reserpinized mice, theophylline caused a dose-dependent rise in body temperature. The response was blocked in animals pretreated with phenoxybenzamine, propranolol and atropine. Single treatment of animals with either SCH 23390 or sulpiride, and also with a combination of the two drugs, decreased the hyperthermia induced by theophylline in reserpinized mice. Pimozide or metergoline did not have any effect in this respect. These data suggest that the hypothermic response to theophylline may be mediated through dopaminergic, cholinergic and serotonergic mechanisms. The hyperthermic action of theophylline in reserpinized animals may be mediated through dopaminergic, cholinergic and adrenergic systems. Overall it seems likely that theophylline interacts with modulatory mechanisms involved in thermoregulation.
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PMID:On the mechanisms by which theophylline changes core body temperature in mice. 808 93

Administration of the selective dopamine D1 and D2 receptor agonists, A 68930 (0.9-60.0 mumol kg-1 s.c.) and quinpirole (0.1-6.0 mumol kg-1 s.c.), produced a dose-dependent decrease in core temperature in the rat. The hypothermia induced by quinpirole (1.5 mumol kg-1) was antagonized by pretreatment with the selective dopamine D2 receptor antagonist, raclopride (1.6 mumol kg-1 s.c.), but not by the dopamine D1 receptor antagonist, SCH 23390 (0.3 mumol kg-1 s.c.), whereas the hypothermia induced by A 68930 (3.8 mumol kg-1) was antagonized by SCH 23390 (0.3 mumol kg-1), but not by raclopride (1.6 mumol kg-1). Together, these results suggest that both dopamine D1 and D2 receptors are specifically involved in the regulation of body temperature in the rat.
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PMID:Evidence for specific involvement of dopamine D1 and D2 receptors in the regulation of body temperature in the rat. 810 71

Chlorpromazine- and haloperidol-induced hypothermia were examined in mice. The alpha 1 receptor agonist phenylephrine partially antagonized the hypothermia, while the dopamine D2 receptor agonist apomorphine did not inhibit it. The central serotonin2 (5-HT2) receptor agonist I-2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) strongly inhibited the chlorpromazine- and haloperidol-induced hypothermia. Both drugs at doses which can elicit hypothermia antagonized head twitch responses mediated by the central 5-HT2 receptor. These results suggest that the chlorpromazine- and haloperidol-induced hypothermia may be mediated by the blockade of the central 5-HT2 receptor.
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PMID:Serotonin2 (5-HT2) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) inhibits chlorpromazine- and haloperidol-induced hypothermia in mice. 859 84


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