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)

Buspirone, a putative serotonin (5-HT)1A partial agonist, did not produce hypothermia in 17 normal volunteers in a placebo controlled, single blind study. Thus, buspirone may be a weaker agonist at those 5-HT1A receptors which mediate hypothermia compared to ipsapirone or gepirone, two other 5-HT1A partial agonists which have been reported to produce hypothermia by a 5-HT1A-mediated mechanism.
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PMID:Buspirone does not produce a 5-HT1A-mediated decrease in temperature in man. 175 Oct 30

1. Azapirones, selective partial agonists at the 5-HT1A receptor subtype, induce hypothermia and corticotropin (ACTH)/cortisol release as specific functional correlates of central 5-HT1A receptor activation. 2. Compared to controls, hypothermic and ACTH/cortisol responses to the azapirone ipsapirone are attenuated in patients with unipolar depression and panic disorder but not in patients with obsessive-compulsive disorder. The impaired thermic and neuroendocrine responses are associated with increased basal cortisol secretion in depressed patients but not in patients with panic disorder. 3. Chronic treatment with the selective 5-HT reuptake inhibitor fluoxetine decreases 5-HT1A receptor-mediated responses in patients with obsessive-compulsive disorder, while long-term treatment with the tricyclic antidepressant amitriptyline further decreases hypothermia following ipsapirone but has no effect on ACTH/cortisol release. 4. Alteration of the 5-HT1A receptor and/or its signal transduction pathways may play a role in the pathophysiology and treatment of anxiety disorders and depression.
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PMID:5-HT1A receptor responsivity in anxiety disorders and depression. 176 90

To study the purported relation of 5-HT1A and 5-HT2 receptors, we chronically injected rats with a low dose of selective 5-HT agonists to induce behavioral tolerance and then tested for cross-tolerance. Acutely, in naive rats, both the putative 5-HT2 agonist DOI and 5-HT1A agonist 8-OH-DPAT induced some behaviors of the "serotonin syndrome" but the two drugs could be differentiated. Only DOI evoked shaking behavior, "skin jerks" (spinal myoclonus), and hyperthermia. Only 8-OH-DPAT induced flat body posture, head weaving, hypothermia, and occasional hindlimb hyperextension (dystonic posture). Both drugs, especially 8-OH-DPAT, evoked forepaw tapping. Chronic (21 day) treatment with DOI prevented DOI-evoked behaviors but not behaviors evoked by 8-OH-DPAT. Behaviors evoked by 8-OH-DPAT and not DOI decreased significantly after chronic 8-OH-DPAT treatment. Development of selective tolerance suggests that putative selective 5-HT2 and 5-HT1A agonists exert both shared and distinctive behavioral effects through separate sites whose relation is behavior-specific. For some behaviors (forepaw myoclonus, shaking behavior, thermoregulation), there is a functional interaction between 5-HT1A and 5-HT2 sites, while for other behaviors (skin jerks, flat body posture, head weaving), there is no interaction.
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PMID:The relation of central 5-HT1A and 5-HT2 receptors: low dose agonist-induced selective tolerance in the rat. 183 98

It has recently been suggested that central 5-HT1A autoreceptors are already desensitised after single-dose 5-HT1A agonist treatment. In turn, this would lead to an attenuated feedback suppression of transmitter release from 5-HT neurones, and thus to enhanced 5-HT synaptic transmission. In the present study in vivo brain microdialysis techniques were used in an attempt to test this hypothesis. The results show that single-dose pretreatment with the reference 5-HT1A receptor agonist 8-hydroxy-2-(din-propylamino)tetralin, 8-OH-DPAT, (i) did not significantly alter the baseline output of 5-HT in the rat ventral hippocampus 24 h later, and (ii) did not alter the release-reducing response to 5-HT1A agonist (8-OH-DPAT, ipsapirone or BMY 7378) challenge under the same conditions. These observations indicate that the functional responsiveness of the 5-HT release-controlling 5-HT1A autoreceptors is maintained after bolus 8-OH-DPAT pretreatment. When related to the acute 8-OH-DPAT-induced reduction in raphe 5-HT1A radioligand binding density recently reported by others, the present results are consistent with a large functional overcapacity of this 5-HT1A receptor population. The mechanism by which 5-HT1A receptor-mediated hypothermia and hyperphagia are rapidly attenuated by a previous large single dose of a 5-HT1A receptor agonist remains to be explained.
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PMID:Single-dose 8-OH-DPAT pretreatment does not induce tachyphylaxis to the 5-HT release-reducing effect of 5-HT1A autoreceptor agonists. 183 41

The novel, naphthylpiperazine 5-HT1A agonist, S 14671 (4-[(thenoyl-2)aminoethyl]-1-(7-methoxynaphtylpiperazine], displayed very high affinity for 5-HT1A binding sites (pKi = 9.3) as compared to the serotonin (5-HT)1A agonists, 8-OH-DPAT (9.2) and (+)-flesinoxan (8.7) and the 5-HT1A partial agonists, buspirone (7.9) and BMY 7378 (8.8). In vivo, S 14671 induced the typical 5-HT1A agonist-induced responses of hypothermia and spontaneous tail-flicks at doses as low as greater than or equal to 5 micrograms/kg s.c. and greater than or equal to 40 micrograms/kg s.c., respectively. In each test, it was about 10-fold more potent than 8-OH-DPAT and 100-fold more potent than (+)-flesinoxan and buspirone. The actions of S 14671 could be blocked by BMY 7378 and the 5-HT1A receptor antagonist, (-)-alprenolol, but not by the 5-HT1C/2 receptor antagonist, ritanserin, nor the 5-HT3 receptor antagonist, ICS 205930. Thus, S 14671 is a novel 5-HT1A ligand of high efficacy and exceptional in vivo potency.
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PMID:S 14671: a novel naphthylpiperazine 5-HT1A agonist of high efficacy and exceptional in vivo potency. 183 84

The behavioural and biochemical profile of the sigma ligand and putative antipsychotic agent, BMY 14802 (alpha-(4-fluorophenyl)-4-(5-fluoro-2- pyrimidinyl)-1-piperazine butanol) has been determined in the mouse and rat. In mice, pretreatment with BMY 14802 attenuated both amphetamine-induced hyperactivity and conditioned avoidance responding, consistent with its previously reported antipsychotic potential. In common with 5-HT1A receptor agonists or partial agonists, BMY 14802 induced (a) a dose-dependent hypothermia in mice; (b) aspects of the 5-HT behavioural syndrome in rats, (c) antagonised mescaline-induced head twitches in mice and (d) generalised to the 8-hydroxy-2-(di-n-propylamino)tetralin discriminative stimulus over the dose range of 3-15 mg/kg. BMY 14802 had appreciable affinity for the 5-HT1A receptor (pIC50 = 6.7 compared to 7.3 for sigma binding) and antagonised forskolin-stimulated adenylate cyclase activity with a pEC50 of 6.2, consistent with an agonist action at this receptor. The results support the involvement of 5-HT1A receptors, but not the sigma binding site, in the behavioural profile of BMY 14802.
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PMID:Behavioural and biochemical evidence of the interaction of the putative antipsychotic agent, BMY 14802 with the 5-HT1A receptor. 183 33

This study was designed to characterize the previously described hypothermic action of norepinephrine (NE) microdialyzed into the medial preoptic area (MPO) of conscious guinea pigs. To this end, the effects on core temperature (Tco) of isotonic pyrogen-free saline (PFS), hypotonic PFS, inactive (oxidized) NE (hypertonic), 5-hydroxytryptamine (5-HT, 10 and 20 micrograms/microliter), PFS with or without 2.4 mM Ca2+, 10 micrograms/microliters NE with Ca2+, and various doses of NE (0.05-60 micrograms/microliters) were compared in a series of studies at an ambient temperature (Ta) of 24 degrees C. The Tco responses to 10 micrograms/microliters NE in a cold (15 +/- 2 degrees C) and a warm (31 +/- 1 degrees C) Ta and during the night in the dark in Ta 24 degrees C were also measured. Bromophenol blue (0.2%) was microdialyzed to assess the extent of diffusion of these dialysates. A stain was found in the MPO, which increased in density but did not spread beyond this region over 3 h of continuous microdialysis. Neither PFS nor the hypotonic and hypertonic solutions had any obvious effect on Tco. Similarly, neither dose of 5-HT evoked a thermal response. Ca2+ added to either PFS or NE did not alter the usual Tco responses to these two solutions. NE induced dose-dependent hypothermia in Ta 24 degrees C. NE microdialyzed in Ta 15 degrees C also produced Tco falls, but these responses were smaller than those in 24 degrees C. NE had no effect in the warm Ta. During the night, NE elicited similar Tco falls, but their recoveries after dialysis ended were slower than during the day.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Microdialysis of norepinephrine into preoptic area of guinea pigs: characteristics of hypothermic effect. 190 44

The effect of ethanol and pentobarbital on in vivo tryptophan hydroxylase activity and its relationship to drug-induced alterations of thermoregulation was examined in long-sleep (LS) and short-sleep (SS) mice. Serotonin function was measured in both the presence and absence of ethanol or pentobarbital in six discrete brain regions. Differences in basal levels of serotonin, 5-hydroxyindole acetic acid or in vivo tryptophan hydroxylase (TpH) activity were found only in the hypothalamus and dorsal raphe nuclei (SS slightly higher). Ethanol (4.2 g/kg i.p) caused significant reductions in in vivo TpH activity in the dorsal and pontine-medullary raphe nuclei and hypothalamus (putative thermoregulatory areas) in both LS (50-60% decrease) and SS (15-30% decrease) mice, but it had no effect on TpH activity in the striatum, cortex or hippocampus. The greater degree of ethanol-induced reduction in TpH activity in LS mice was associated with a greater degree of hypothermia (LS, 4.2 degrees C vs SS, 2.0 degrees C). Pentobarbital had equivalent effects in LS and SS mice on TpH activity in central nervous system thermoregulatory areas (decreases of 40-60%) and on body temperature (decreases of 6.8-7.5 degrees C). When the mice were given ethanol at an elevated environmental temperature (34 degrees C) the hypothermia was almost abolished completely, but depressant effects on TpH activity remained, suggesting that ethanol-induced decreases in TpH activity were direct effects and not secondary to hypothermia. Alterations in ethanol or pentobarbital elimination did not appear to account for the observed differences.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotoninergic involvement in ethanol-induced alterations of thermoregulation in long-sleep and short-sleep mice. 194 31

A series of 2-phenyl-2-(1-hydroxycycloalkyl)ethylamine derivatives was examined for the ability to inhibit both rat brain imipramine receptor binding and the synaptosomal uptake of norepinephrine (NE) and serotonin (5-HT). Neurotransmitter uptake inhibition was highest for a subset of 2-phenyl-2-(1-hydroxycyclohexyl)dimethylethylamines in which the aryl ring has a halogen or methoxy substituent at the 3- and/or 4-positions. Potential antidepressant activity in this subset was assayed in three rodent models--the antagonism of reserpine-induced hypothermia, the antagonism of histamine-induced ACTH release, and the ability to reduce noradrenergic responsiveness in the rat pineal gland. An acute effect seen in the rat pineal gland with several analogues, including 1-[1-(3,4-dichlorophenyl)-2-(dimethylamino)ethyl]cyclohexanol (23) and 1-[2-(dimethylamino)-1)-(4-methoxyphenyl)ethyl]cyclohexanol (4), was taken as a possible correlate of a rapid onset of antidepressant activity. Compound 4 (venlafaxine) is presently undergoing clinical evaluation.
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PMID:2-Phenyl-2-(1-hydroxycycloalkyl)ethylamine derivatives: synthesis and antidepressant activity. 197 13

The effects of peripherally administered serotonin (5-HT) on the rectal temperature were investigated. 5-HT i.p. induced a dose-dependent hypothermia in mice. The hypothermic effects of 5-HT were strongly antagonized by the 5-HT1 and 5-HT2 receptor antagonist methysergide and the 5-HT2 receptor antagonist ketanserin. However, the 5-HT1 receptor antagonist pindolol and the 5-HT3 receptor antagonist ICS 205-930 were without effect. In addition, the peripheral 5-HT2 receptor antagonist xylamidine strongly reduced 5-HT-induced hypothermia. These results indicate that the activation of the peripheral 5-HT2 receptors induces hypothermia, although the central 5-HT2 receptors have been suggested to relate to hyperthermia.
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PMID:Activation of peripheral serotonin2 receptors induces hypothermia in mice. 199 84


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