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 effects of serotonin precursors, tryptophan (TP) and L-5-hydroxytryptophan (5-HTP), administered together with peripheral decarboxylase inhibitor -- Ro 4-4602 on the rectal body temperature of rats was studied. TP caused a significant hypothermia which was prevented by pretreatment with p-chlorophenylalanine (PCPA), the serotonin synthesis inhibitor. 5-HTP did not influence the body temperature or slightly decreased it. However, the significant hypothermizing effect of 5-HTP was observed in rats pretreated with spiroperidol, haloperidol or phenoxybenzamine. Methysergide or cyproheptadine -- compounds regarded as potent serotonin receptor blockers -- did not prevent the TP-induced hypothermia. In methysergide pretreated rats 5-HTP produced a considerable hyperthermia. Cyproheptadine did not influence the effects of 5-HTP on the body temperature. The results obtained suggest that cyproheptadine and methysergide fail to block those central serotonin receptors which produce hypothermia after their stimulation.
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PMID:The influence of serotonergic agents on the body temperature. 13 32

Impromidine, a highly potent histamine H2-receptor agonist, given i.v. at doses of 3.1-62 nmole, induced a dose-dependent hypothermia in the rat with a maximal effect after 15 min. Cimetidine, an H2-receptor antagonist, having no effect when administered alone, antagonized the hypothermic action of impromidine. Two antiserotoninergic agents, p-chlorophenylalanine and metergoline, and chronic treatment with an antidepressant mianserine reduced the impromidine-induced hypothermia. It is suggested that the impromidine-induced hypothermia is an H2-receptor-mediated phenomenon, and the antagonizing effect of mianserine is related to serotonin receptor blocking activity of the drug rather than to its direct H2-receptor antagonism.
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PMID:Impromidine-induced hypothermia in rats: effect of cimetidine and mianserine. 628 72

Meta-chlorophenylpiperazine (m-CPP), a probe of central serotonergic function, elevates core temperature in rodents, nonhuman primates, and humans via serotonin receptor-mediated mechanisms. To further characterize the thermoregulatory aspects of this response, we studied 16 healthy volunteers using multiple core and skin temperature recording sites. Compared to placebo, intravenous m-CPP (0.08 mg/kg) produced statistically significant biphasic changes in rectal temperature, characterized by initial hypothermia (-0.04 degrees C at 12 minutes) followed by progressive hyperthermia (+0.17 degrees C at 90 minutes). m-CPP also produced significant increases in plasma norepinephrine concentrations. Analysis of the skin temperature recordings suggests that the effector mechanism primarily responsible for m-CPP-induced core hyperthermia is increased metabolic thermogenesis. Individual differences in the magnitude of the hyperthermia were independent of m-CPP plasma concentrations but were found to be linearly correlated with the level of the previous night's core rectal temperature minimum and mean. It appears that m-CPP activates a mode of metabolic thermogenesis governed by a nocturnally sensitive proportional control mechanism. The operation of such a proportional controller is characterized by a set point and a gain, and has been implicated in the general economy of mammalian energy balance.
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PMID:Serotonin and thermoregulation. Physiologic and pharmacologic aspects of control revealed by intravenous m-CPP in normal human subjects. 859 22

Ligands with varying intrinsic activity and selectivity for the various subtypes of the serotonin receptor were tested in the rat pup ultrasonic vocalization (USV) model, a putative animal model reflecting anxiety. USV were elicited by isolating rat pups from their mother and littermates by placing them on a warm (37 degrees C) or a cold (18 degrees C) plate. Concurrently, the negative geotaxic (NG) response and rectal temperature were determined to assess the potentially sedative and hypothermic effects of putative anxiolytics. USV were reduced at low doses and in both temperature conditions by the full 5-HT1A receptor agonists flesinoxan and 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin.HBr) and the partial 5-HT1A receptor agonists buspirone, ipsapirone and BMY 7378 (2-[4-[4-[2-pyrimidinyl]-1,2-piperazinyl]butyl]-1,2-benzi-isoth iozol-3-(2H)one-1,1-dioxide. 2HCl). The 5-HT1A receptor antagonists NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phtalimido)-butyl]piperazide.2H Cl), (+/-)-WAY 100,135 (+/-)-(N-tert-butyl-3(4-(2-methoxy phenyl)piperazin-1 -yl)-2-phenyl propionamine.2HCl), and ((S)-UH-301 (S)-5-fluoro-8-hydroxy-2-(di-n-propyl-amino)tetralin.HBr) reduced USV at higher doses and only in one of both test conditions. The selective 5-HT1A receptor antagonist DU 125530 (2-[4-[4[(7-chloro-2,3dihydro-4-benzodioxin-5-yl)-1-piperazi nyl]butyl]-1,2-benzisothiazol-3(2H)-one-1,1, dioxide, monomesylate), did not influence USV at the cold plate up to high doses, although concomitantly the negative geotaxis was disturbed. The negative geotaxis was impaired after all 5-HT1A receptor ligands, except BMY 7378 and (+/-)-WAY 100,135. Hypothermia coincided with USV-suppression, except for NAN-190 and (S)-UH-301. The USV-suppressing action of flesinoxan (3 mg/kg) could be antagonized by DU 125530, but not its NG effect. However, the hypothermia induced by flesinoxan was antagonized by DU 125530. USV were also suppressed by the 5-HT uptake inhibitors fluvoxamine (both warm and cold plate) and clomipramine (only warm plate). The tricyclic antidepressant imipramine only decreased USV on the cold plate, however, in a U-shaped dose-response curve. At the highest dose tested, no decrease was present. The 5-HT uptake stimulant tianeptine reduced USV under both conditions. Fluvoxamine had no side effects, clomipramine induced hypothermia and tianeptine clearly had sedative properties. The 5-HT1B/2C receptor agonist TFMPP (trifluorometaphenylpiperazine) stimulated USV at a low dose at the cold plate and suppressed USV at a high dose under both conditions. The 5-HT2A/2C receptor antagonist ketanserine enhanced USV at low doses under both conditions and had no effect at a higher dose. Concurrently heavy sedation and hypothermia occurred. The 5-HT3 receptor agonist phenylbiguanide and the 5-HT3 receptor antagonist ondansetron had no effect in this paradigm. Clearly, subtypes of the 5-HT receptor affect rat pup USV differentially.
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PMID:Ultrasonic vocalizations in rat pups: effects of serotonergic ligands. 988 14

Dietary dehydroepiandrosterone (DHEA) reduces food intake in mice, and this response is under genetic control. Moreover, both food restriction and DHEA can prevent or ameliorate certain diseases and mediate other biological effects. Mice fed DHEA (0.45% w/w of food) and mice pair-fed to these mice (food restricted) for 8 weeks were tested for changes in body temperature. DHEA was more efficient than food restriction alone in causing hypothermia. DHEA injected intraperitoneally also induced hypothermia that reached a nadir at 1 to 2 hr, and slowly recovered by 20 to 24 hr. This effect was dose dependent (0.5-50 mg). Each mouse strain tested (four) was susceptible to this effect, suggesting that the genetics differ for induction of hypophagia and induction of hypothermia. Because serotonin and dopamine can regulate (decrease) body temperature, we treated mice with haloperidol (dopamine receptor antagonist), 5,7-dihydroxytryptamine (serotonin production inhibitor), or ritanserin (serotonin receptor antagonist) prior to injection of DHEA. All of these agents increased rather than decreased the hypothermic effects of DHEA. DHEA metabolites that are proximate (5-androstene-3beta, 17beta-diol and androstenedione) or further downstream (estradiol-17beta) were much less effective than DHEA in inducing hypothermia. However, the DHEA analog, 16alpha-chloroepiandrosterone, was as active as DHEA. Thus, DHEA administered parentally seems to act directly on temperature-regulating sites in the body. These results suggest that DHEA induces hypothermia independent of its ability to cause food restriction, to affect serotonin or dopamine functions, or to act via its downstream steroid metabolites.
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PMID:Decrease of core body temperature in mice by dehydroepiandrosterone. 1203 27

Central dopamine-2 (D2) receptors are importantly involved in the pathogenesis and treatment of schizophrenia. Central D2 receptors are also involved in thermoregulation. Recently, a type of central nervous system proportional control thermostat was described that governs the magnitude of several serotonin receptor-mediated core body thermoregulatory responses in proportion to both the amount of nocturnal melatonin secreted and the minimum level of nocturnal core body temperature (Tmin). The present study investigated whether the magnitude of D2 receptor-mediated hypothermia--a putative index of central D2 receptor sensitivity--is also regulated by this proportional control thermostat in humans. Twenty healthy subjects had their 02:00 h melatonin concentrations (MT2am) and Tmin measured during consecutive sleep episodes and their core body temperature responses (TAUC) measured the next two mornings after oral ingestion of either the D2 receptor agonist bromocriptine 3.125 mg or placebo. We found that the bromocriptine-induced TAUC was significantly and independently correlated with both Tmin and MT2am. In conclusion, D2 receptor-mediated hypothermia, an index of central D2 receptor sensitivity, is regulated by a proportional control thermostat in humans. The abnormal D2 receptor function in schizophrenia could be related to dysfunction of this thermostat.
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PMID:Regulation of central dopamine-2 receptor sensitivity by a proportional control thermostat in humans. 1526 1

On the basis of our earlier studies with the serotonin receptor ligands in the group of 1,3-dimethyl-3,7-dihydropurine-2,6-dione derivatives, a series of new arylpiperazinylalkyl and tetrahydroisoquinolinylalkyl analogs of 8-alkoxy-1,3-dimethyl-3,7-dihydropurine-2,6-dione (10-25) and 1,3-dimethyl-7,9-dihydro-3H-purine-2,6,8-trione (26-30) were synthesized and their 5-HT(1A), 5-HT(2A), and 5-HT(7) receptor affinities were determined. The new compounds 17, 18, 20, and 21 were found to be highly active 5-HT(1A) receptor ligands (K(i)=11-19nM) with diversified affinity for 5-HT(2A) receptors (K(i)=15-253nM). Compounds 12, 13, 15, and 19 were moderately potent 5-HT(2A) ligands (K(i)=23-57nM), whereas 17, 18, 24, and 25 showed distinct affinity for 5-HT(7) receptors (K(i)=51-83nM). Purine-2,6,8-triones showed weak affinities for 5-HT(1A) and 5-HT(7) receptors; among them, 27 and 29 were classified as 5-HT(2A) receptor ligands. The selected compounds 17 and 21 were pharmacologically evaluated to determine their functional activities at pre-(hypothermia in mice) and post-(lower lip retraction in rats) synaptic 5-HT(1A) receptors. Compound 17 showed features of a potential agonist of pre- and post-synaptic 5-HT(1A) receptors, whereas 21 was classified as a potential, weak partial agonist of postsynaptic sites. Last of all, the most interesting compound 17 tested in behavioral models showed potential anxiolytic and antidepressant activities.
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PMID:7-Arylpiperazinylalkyl and 7-tetrahydroisoquinolinylalkyl derivatives of 8-alkoxy-purine-2,6-dione and some of their purine-2,6,8-trione analogs as 5-HT(1A), 5-HT(2A), and 5-HT(7) serotonin receptor ligands. 1751 14

The serotonin type 3 (5-HT(3)) receptor is unique among the seven recognized serotonin receptor "families". The existence serotonin type 3 receptor (5-HT(3)) in neuro-anatomical regions stimulated the research interest for novel therapeutic targets such as anxiety, depression, nociception and cognitive function. In the current study, (4-benzylpiperazin-1-yl) (quinoxalin-2-yl) methanone (QCF-3), a novel 5-HT(3) receptor antagonist, with an optimal log P (the logarithm of the ratio of the concentrations of the un-ionized solute in the solvents is called log P) and significant pA2 value (is a negative logarithm of the molar concentration of antagonist required to reduce the effect of multiple dose agonist to that of single dose) was screened for its anti-depressant potential using rodent behavioral models of depression. Psycho-pharmacological investigations involved acute and chronic treatment (14 days) with QCF-3 and assessment of behavior during the forced swim test (FST) and tail suspension test (TST) in mice and olfactory bulbectomised rats. A dose response study in mice revealed an initial anti-depressant-like effect of QCF-3 (0.5-4 mg/kg, ip) in the FST and TST. Interaction studies showed that QCF-3 (1 and 2 mg/kg) significantly enhanced the antidepressant action of fluoxetine and bupropion in the FST and TST, respectively. QCF-3 (1 and 2 mg/kg) potentiated the 5-hydroxytryptophan (5-HTP) induced head twitches response in mice and reversed reserpine-induced hypothermia in rats. Further, OBX rats exhibited behavioral anomalies in the open field and hyper-emotionality tests that were attenuated by chronic QCF-3 treatment. In conclusion, this behavioral study describes an antidepressant-like effect of QCF-3 in rodent behavioral models of depression.
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PMID:Effect of acute and chronic treatment with QCF-3 (4-benzylpiperazin-1-yl) (quinoxalin-2-yl) methanone, a novel 5-HT(3) receptor antagonist, in animal models of depression. 2050 79

We previously demonstrated that mice with reduced expression of the vesicular monoamine transporter 2 (VMAT2 LO) undergo age-related degeneration of the catecholamine-producing neurons of the substantia nigra pars compacta and locus ceruleus and exhibit motor disturbances and depressive-like behavior. In this work, we investigated the effects of reduced vesicular transport on the function and viability of serotonin neurons in these mice. Adult (4-6 months of age), VMAT2 LO mice exhibit dramatically reduced (90%) serotonin release capacity, as measured by fast scan cyclic voltammetry. We observed changes in serotonin receptor responsivity in in vivo pharmacological assays. Aged (months) VMAT2 LO mice exhibited abolished 5-HT1A autoreceptor sensitivity, as determined by 8-OH-DPAT (0.1 mg/kg) induction of hypothermia. When challenged with the 5HT2 agonist, 2,5-dimethoxy-4-iodoamphetamine (1 mg/kg), VMAT2 LO mice exhibited a marked increase (50%) in head twitch responses. We observed sparing of serotonergic terminals in aged mice (18-24 months) throughout the forebrain by SERT immunohistochemistry and [(3)H]-paroxetine binding in striatal homogenates of aged VMAT2 LO mice. In contrast to their loss of catecholamine neurons of the substantia nigra and locus ceruleus, aged VMAT2 LO mice do not exhibit a change in the number of serotonergic (TPH2+) neurons within the dorsal raphe, as measured by unbiased stereology at 26-30 months. Collectively, these data indicate that reduced vesicular monoamine transport significantly disrupts serotonergic signaling, but does not drive degeneration of serotonin neurons.
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PMID:Reduced vesicular monoamine transport disrupts serotonin signaling but does not cause serotonergic degeneration. 2642 5