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)

Two new congeners, 4-(chloropropyl)-1-(2-quinolyl)piperazine- and 2-[3-[4-[2-(quinolyl)]-1-piperazinyl]propyl]-1,2,4-triazolo] 4,3-a]pyridin-3(2H)-one, of trazodone were synthesized and found to be potent and selective inhibitors of synaptosomal uptake of 5-hydroxytryptamine [5-HT, serotonin; IC50 = norepinephrine greater than 5 microM, 5-HT = 210-890 nM], with minimal effects in antagonizing (-)-apomorphine-induced climbing behavior and suppression of spontaneous locomotor activity in mice (ED50 greater than 50 mg/kg). The two compounds behaved like atypical antidepressants, since they weakly antagonized reserpine-induced hypothermia. The acute toxicity studies have shown that these compounds were less lethal when compared with imipramine or quipazine. Furthermore, chronic treatments (20 mg/kg, daily for 10 and 21 days) significantly decreased the isoprenaline-induced increase in cyclic AMP in the rat brain cortex, suggesting desensitization of beta-adrenoceptors. These findings point to the effects of these compounds as potential antidepressants dealing with specific serotonergic mechanisms.
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PMID:New hybrids of quipazine and trazodone as selective inhibitors of uptake of 5-hydroxytryptamine. 132 Jan 18

The interaction at 5-hydroxytryptamine (5-HT) receptors of the novel naphtylpiperazine, S 14671 (1-[2-(2-thenoylamino)ethyl]-4[1-(7- methoxynaphtyl)]piperazine), was compared to that of the 5-HT1A ligands, 8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT), WY 50,324 [N-(29(4-(2-pyrimidinyl)-1-piperazinyl)ethyl)tricyclo(3.3.1.1(3,7) )- decane-1-carboxamide], (+)-flesinoxan, buspirone and BMY 7378 [(8-[2-[4-(2-methoxyphenyl)- 1-piperazinyl]ethyl]-8-azaspirol[-4-]-decane-7,9-dione 2HCl]. S 14671 showed a very high affinity for 5-HT1A sites (pKi, 9.3) as compared to the reference ligands (pKi values, 9.2, 8.7, 8.7, 7.9 and 8.7, respectively). S 14671 bound in an apparently competitive manner and, in distinction to the reference compounds, possessed a Hill Coefficient (1.4) significantly superior to 1. Although showing low affinity at 5-HT1B and 5-HT3 sites, S 14671 displayed significant affinity at both 5-HT1C and 5-HT2 sites; pKi, 7.8 in each case. Furthermore, S 14671 acted as an antagonist of 5-HT-stimulated phosphoinositide turnover in rat choroid plexus (5-HT1C) and cortex (5-HT2). In vivo, upon s.c. administration, S 14671 acted as a high efficacy agonist in models of 5-HT1A receptor-mediated activity: induction of flat-body posture, spontaneous tail-flicks, hypothermia and corticosterone secretion and inhibition of morphine-induced antinociception. In every test, S 14671 was the most potent compound: it was active at doses as low as 5 micrograms/kg s.c. Relative potency across all tests was S 14671 greater than 8-OH-DPAT greater than WY 50,324 greater than (+)-flesinoxan greater than buspirone with BMY 7378 too weak for comparison to be meaningful. The action of S 14671 in 5-HT1A tests was blocked by BMY 7378 and the 5-HT1A antagonist, (-)-alprenolol, but unaffected by the 5-HT1C/2 antagonist, ritanserin, and the 5-HT3 antagonist, ondansetron. Activation of postsynaptic 5-HT1A receptors was confirmed in 5,7-dihydroxytryptamine-lesioned rats, in which the potency of S 14671 to elicit spontaneous tail-flicks was potentiated. Activation of presynaptic receptors was demonstrated by inhibition of the electrical activity of the dorsal raphe nucleus with the following order of relative potency: S 14671 greater than 8-OH-DPAT greater than WY 50,324 greater than BMY 7378 greater than buspirone. Spiperone, which acts as a pure 5-HT1A antagonist at raphe 5-HT1A receptors, blocked the action of S 14671. In conclusion, S 14671 is a structurally novel ligand manifesting high efficacy and exceptional potency at both pre- and postsynaptic 5-HT1A receptors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:S 14671: a naphtylpiperazine 5-hydroxytryptamine1A agonist of exceptional potency and high efficacy possessing antagonist activity at 5-hydroxytryptamine1C/2 receptors. 132 50

The effect of repeated treatment (5 and 10 mg/kg, po, twice daily, 14 days) with sertraline and citalopram (antidepressants which selectively inhibit the reuptake of 5-hydroxytryptamine (5-HT)) on the responsiveness of different 5-HT receptors to their agonists, was examined in rats and mice. Sertraline and citalopram (both at a dose 5 and 10 mg/kg) antagonized (the first one more potently) the hypothermia induced in mice by 8-OH-DPAT (a 5-HT1A agonist), but not the behavioural syndrome induced in rats by this substance. The m-chlorophenylpiperazine-induced hypothermia in mice (a 5-HT1B effect) was increased by sertraline and citalopram (only in a dose of 10 mg/kg). Both antidepressants, given repeatedly (as well acutely) attenuated exploratory hypoactivity induced in rats by m-chlorophenylpiperazine (a 5-HT1C effect). L-5-HTP-induced head twitches in mice (5-HT2 effect) were antagonized dose-dependently by both repeated sertraline and citalopram. Both antidepressants (citalopram only in higher dose) reduced the fenfluramine-induced hyperthermia in rats (5-HT2 effect). The results indicate that sertraline and citalopram given repeatedly decrease the responsiveness of 5-HT1A (presynaptic) and 5-HT2 receptors but increase the responsiveness of 5-HT1B receptors to respective agonists.
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PMID:Effects of sertraline and citalopram given repeatedly on the responsiveness of 5-HT receptor subpopulations. 138 65

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

This study was performed to investigate the pulmonary vascular reactivity during hypothermia. It was found that the pulmonary vessels were more sensitive to alveolar hypoxia in hypothermic dogs, and that hypoxic pulmonary vasoconstriction (HPV) was enhanced, which could be inhibited by alpha 1-adrenoceptor blocker prazosin. The concentration of arterial plasma norepinephrine (NE) increased in dogs with hypothermia or in those with hypothermia plus hypoxia, but there was no significant difference between these two groups. The plasma level of 5-hydroxytryptamine (5-HT) was reduced during hypoxia in hypothermic dogs. Increase in plasma 6-keto-PGF1 alpha, which appeared in hypoxic dogs, was not observed during hypoxia in hypothermic dogs. These findings suggest that a potentiation in the sensitivity and reactivity of alpha-adrenoceptor in pulmonary vessels and a decrease in the modulation of PGI2 might be responsible for the enhancement of HPV. 5-HT seemed not to play a contributing role in the alteration of HPV.
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PMID:Alteration in hypoxic pulmonary vasoconstriction during hypothermia in dogs. 145 1

5-Hydroxytryptamine (5-HT) was injected into the rostral ventrolateral medulla (RVLM) in urethane-anaesthetized rats and its effect assessed on thermoregulatory and non-thermoregulatory cutaneous circulations by the measurement of skin surface temperatures. 5-Hydroxytryptamine (5-50 nmol) produced a dose-related fall in blood pressure (5-20 mmHg) and an increase in tail and plantar foot surface temperatures, indicative of dilatation in the underlying cutaneous circulations. If heat was not applied to the animal, the body temperature fell by 1-2 degrees C within 15-25 min. The decrease in tail and foot temperatures, produced by low frequency (25 Hz, 5 min) electrical stimulation, was antagonized by the injection of 5-HT at the site of stimulation. 5-Carboxyamidotryptamine (2.5-20 nmol) and flesinoxan (5-25 nmol) produced responses similar to 5-HT. The 5-HT2 receptor agonist, alpha-methyl 5-hydroxytryptamine (alpha-methyl 5-HT, 5.5-100 nmol) was only effective in increasing tail and plantar foot temperatures, at dose levels above 25 nmol. However, in a few sites restricted to the anterior region of the RVLM, alpha-methyl 5-HT (11 nmol) evoked a small decrease in tail and foot temperatures, indicative of a constrictor effect, without influencing resting cardiovascular parameters. The results are discussed in relation to the central mechanisms which underly the hypothermia and hyperthermia produced by 5-HT1A and 5-HT2 receptor agonists.
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PMID:Changes in the tail surface temperature of the rat following injection of 5-hydroxytryptamine into the ventrolateral medulla. 152 3

Isometric contraction of isolated guinea-pig taenia caeci was induced with acetylcholine (ACh) and 5-hydroxytryptamine (5-HT) at 37 and 30 degrees C to investigate the effect of hypothermia on the response of smooth muscle to neurotransmitters. Lowering the temperature increased the amplitude of contraction in response to 10(-6) M ACh. Contraction in response to 10(-6) M 5-HT was also greater at 30 degrees C. 5-HT-contraction was not inhibited by atropine, but was inhibited by ketanserin. Calcium-contraction was also induced in an isosmotic high potassium solution. The amplitude of the contraction elicited by 5 x 10(-3) M Ca was significantly greater at 30 degrees C, and was inhibited by verapamil. The amplitude of the contractile response to 5 x 10(-3) M caffeine was also greater at 30 degrees C than at 37 degrees C. The finding that both calcium- and caffeine-contraction were enhanced at low temperature raises the possibility that intracellular calcium participate in cold-induced enhancement of contraction.
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PMID:Hypothermia enhances contractile responses of the guinea pig taenia caeci to acetylcholine, 5-hydroxytryptamine, caffeine and calcium. 157 74

A study was conducted to investigate changes in monoamine metabolism in the brain of rats with acute ischemic hepatic failure (AHF) induced by two-stage hepatic devascularization. Strict artificial cardiopulmonary management was used to exclude possible confounding effects of hypotension, hypothermia and hypoxemia that often appear in AHF. Rats were put in an incubator at 34 degrees C before the ligation of the hepatic artery (second stage operation), tracheotomized and ventilated artificially throughout the remaining experimental periods. No significant difference was observed in physiological parameters, including body temperature, pulse rate and systolic arterial blood pressure or PaO2 between AHF and sham operated rats. Brain levels of norepinephrine (NE) and its metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA), and serotonin (5-hydroxytryptamine, 5HT) and its metabolite 5-hydroxyindoleacetic acid (5HIAA) were determined by HPLC-voltametry. AHF rats showed significantly higher MHPG, DOPAC, 5HIAA and lower NE levels in the brain compared to controls. In addition, a significant negative correlation between NE and tyrosine (Tyr), a significant positive correlation between MHPG and Tyr or phenylalanine (Phe), and a significant positive correlation between DOPAC and Tyr or Phe were observed. In conclusion, the changes in monoamine metabolism in the brain of AHF rats are clearly induced specifically by hepatic failure itself, possibly through an altered metabolism of amino acids.
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PMID:Changes in brain monoamine metabolism in rats with acute ischemic hepatic failure under artificial cardiopulmonary management. 157 24

Hypothermia combined with chemical cardioplegia is routinely used clinically for perioperative myocardial protection and for donor heart preservation. Profound hypothermia can have an adverse influence on post-preservation endothelial and myocardial functions. In this study, we investigated the effect of temperature on endothelial and myocardial functions following global cardiac ischaemia in the isolated rat heart. A 5-hydroxytryptamine (5-HT)-induced increase in coronary flow was used as a selective probe to assess endothelial function, while myocardial function was measured by a working rat heart model. After recording control observations for endothelial and myocardial functions, hearts were kept ischaemic for 30 or 60 min without cardioplegia (groups 1 and 2, respectively) and for 60, 90 or 120 min following a single infusion of St. Thomas' Hospital solution (groups 3, 4 and 5, respectively). In each group, hearts were kept ischaemic at 20 degrees C or at 4 degrees C (n = 12 in each group). Endothelial and myocardial functions were reevaluated and compared with control values.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Improved preservation of endothelial function at 4 degrees C. 158 Oct 84

To evaluate 5-hydroxytryptamine1A receptor responsivity in obsessive-compulsive disorder, we examined hypothermic, neuroendocrine, and behavioral responses to the selective 5-hydroxytryptamine1A receptor ligand ipsapirone in patients with primary obsessive-compulsive disorder and healthy controls. Twelve patients and 22 controls received a single dose of ipsapirone, 0.3 mg/kg, or placebo under double-blind, random assignment conditions. Ipsapirone induced hypothermia and release of corticotropin and cortisol but had no effect on behavior, including obsessive or compulsive symptoms. Thermoregulatory and neuroendocrine responses to ipsapirone were not consistently different between healthy controls and patients with obsessive-compulsive disorder. These results provide no direct support for the hypothesis that a serotonergic dysfunction related to 5-hydroxytryptamine1A receptors may be linked to the pathophysiologic characteristics of obsessive-compulsive disorder and point to the need for the evaluation of other 5-hydroxytryptamine receptor subtypes. Future studies of the responsivity of 5-hydroxytryptamine1A receptors to direct-acting ligands, such as ipsapirone, should facilitate assessment of the integrity of the 5-hydroxytryptamine system and its involvement in antiobsessional drug effects.
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PMID:5-Hydroxytryptamine1A receptor responsivity in obsessive-compulsive disorder. Comparison of patients and controls. 167 53


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