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)

LB50016 was characterized as a selective and potent 5-HT1A receptor agonist and evaluate its anxiolytic and antidepressant activities. It shows high affinity for 5-HT1A receptor, moderate affinity for alpha 2 adrenergic and 5-HT2A receptors and no significant affinity for other receptors tested. Hypothermia and increased serum corticosterone level were observed in LB50016-treated rats, which are mediated mostly by post synaptic 5-HT1A receptor activation. In the mouse forced swim model for depression, LB50016-elicited dose-dependent reductions in immobility time, showing ED50 of approximately 3 mg/kg i.p., which was blocked by pretreatment of NAN-190, 5-HT1A antagonist. In face-to-face test for anxiolytic activity in mice, estimated ED50 was 2 mg/kg, i.p. In isolation-induced aggression test with mice, fifty-fold increases in latency to attack were observed at 30 min and last up to 4 h after LB50016 treatment (3 mg/kg, i.p.). Taken together, LB50016-induced pharmacological activities are mediated by activation of 5-HT1A receptors, offering an effective therapeutic candidate in the management of anxiety and depression in humans.
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PMID:Pharmacological characterization of LB50016, N-(4-amino)butyl 3-phenylpyrrolidine derivative, as a new 5-HT1A receptor agonist. 1023 May 6

Management of Blunt hepatic injuries is dramatically modified since early 80's. Non operative management is presently used in over 80% of all cases, irrespective of haemoperitoneum and grade of injury. Close observation of the patient is requested. Laparotomy or laparoscopy must be decided in any case of suspected missed injury. Laparotomy is used for worse hemodynamic status. Peroperative mortality is mainly attributed to haemorrhage. Aggressive surgery has progressively given place to more conservative techniques. Understanding of coagulopathy related to massive transfusions, acidosis and hypothermia led to enhance efficacy of manual compression of the injured liver and of perihepatic packing and planned reoperation. In survivors this abbreviated laparotomy has pitfalls and complications which must be known, mainly rebleeding and abdominal compartment syndrome. Decision of very early reoperation is most difficult to take.
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PMID:[Treatment of blunt trauma to the liver]. 1054 8

The concept of the therapeutic window of opportunity in ischemic neuronal injury and understanding the necessity of well organized stroke services revolutionized the management of acute ischemic stroke during the last years of the second millennium. Thrombolysis with IV rt-PA within 3 hours from the onset of symptoms is an established therapy for selected patients. The challenge of stroke therapy at the outset of this millennium is how to translate basic pathophysiologic evidence of ischemic neuronal injury into novel neuroprotective therapies either independently or combined with thrombolysis. Great hopes are placed in identification of pivotal molecular events in ischemic brain tissue and design of effective pharmacological interventions to target them. Aggressive, invasive procedures are also being developed and therapies such as intra-arterial clot lysis, hemicraniectomy and mild hypothermia may improve the bleakest outcomes associated with the most severe forms of ischemic stroke, but their role must be rigorously evaluated. There is, however, no need to wait for future breakthroughs. The existing evidence strongly implies that good care of patients with stroke starts with organization of the entire stroke chain; from the prehospital scene, through the emergency room, to the stroke unit. Without structured stroke services no pharmacological or intervening therapy is likely to improve the outcome of the patient with a stroke.
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PMID:The future of stroke treatment. 1075 38

To elucidate the relative contribution of somatodendritic 5-HT(1A) autoreceptors and postsynaptic 5-HT(1A) receptors in the specific anti-aggressive properties of 5-HT(1A) receptor agonists, the influence of the novel benzodioxopiperazine compound S-15535, which behaves in vivo as a competitive antagonist at postsynaptic 5-HT(1A) receptors and as an agonist at 5-HT(1A) autoreceptors, upon offensive and defensive aggression was investigated in wild-type rats using a resident-intruder paradigm. S-15535 exerted a potent dose-dependent decrease in offensive, but not defensive, aggressive behavior (inhibitory dose (ID)(50) = 1.11 mg/kg). This anti-aggressive profile was roughly similar to that of the potent pre- and postsynaptic 5-HT(1A) full agonist alnespirone (ID(50) = 1. 24). The drug's profound anti-aggressive actions were not accompanied by sedative side effects or signs of the "5-HT(1A) receptor-mediated behavioral syndrome," which are characteristically induced by prototypical 5-HT(1A) receptor agonists like 8-OH-DPAT and buspirone. The selective pre- and postsynaptic 5-HT(1A) antagonist WAY-100635, which was inactive given alone, abolished the anti-aggressive effects of S-15535 and alnespirone, thereby confirming the involvement of 5-HT(1A) receptors. Furthermore, combined administration of S-15535 and alnespirone elicited an additive anti-aggressive effect, providing further support for somatodendritic 5-HT(1A) receptor involvement. Finally, the postsynaptic 5-HT(1A) antagonistic properties of S-15535 were confirmed by showing blockade of the alnespirone-induced hypothermia, a postsynaptic 5-HT(1A) mediated response in the rat. These data provide extensive evidence that the anti-aggressive effects of 5-HT(1A) receptor agonists are expressed via their action on somatodendritic 5-HT(1A) autoreceptors, thereby most likely attenuating intruder-activated serotonergic neurotransmission.
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PMID:Somatodendritic 5-HT(1A) autoreceptors mediate the anti-aggressive actions of 5-HT(1A) receptor agonists in rats: an ethopharmacological study with S-15535, alnespirone, and WAY-100635. 1086 83

The action of diazepam (0.0, 1.0, and 2.0 mg/kg) and the serotonergic compounds buspirone (0.0, 2.5, and 5.0 mg/kg) and 8-OH-DPAT (0.0, 0.1, and 1.0 mg/kg) on maternal behavior and aggression were studied. An activity test was made after these treatments to control for unspecific actions due to motor impairment. Diazepam and buspirone dose-dependently inhibited the expression of maternal aggression and the active components of maternal behavior such as retrieving and nest building. 8-OH-DPAT did not affect these behaviors. 8-OH-DPAT (1.0 mg/kg) provoked the serotonergic syndrome and hypothermia; however, ovariectomized animals showed more signs of the syndrome and a decrease in body temperature after 8-OH-DPAT than lactating rats. Buspirone, but not the other anxiolytics, reduced motor activity. The role of drugs acting at the serotonergic, dopaminergic, and GABA-benzodiazepine systems in the control of maternal behavior and aggression is discussed.
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PMID:Inhibitory effect of buspirone and diazepam, but not of 8-OH-DPAT, on maternal behavior and aggression. 1088 Jun 95

When faced by an external aggression such as shock, sepsis, burns or surgery, the body develops a response, known as stress, comprising hypermetabolism and hypercatabolism related to an alteration in tissue sensitivity to insulin. This alteration seems to be rooted in the transmembrane protein GLUT-4 which takes care of the cell uptake of glucose in skeletal muscle. As a result, there are alterations in the metabolism of carbohydrates, fats and proteins (reduction of immunoglobulins). In the case of surgery, it has been shown that, on the one hand, factors such as rest, pre-operative fasting or the release of inflammatory response factors constrain an even greater alteration in the sensitivity to insulin; and on the other hand that the degree of resistance to insulin depends on the magnitude of the surgery, its duration, bleeding, or on hypothermia and extracorporeal circulation in the case of heart surgery. These metabolic alterations may lead to an increase in the number of infections, mean stay in hospital, and even lead to diabetes mellitus in the long term. Over the last few years, all of this has led several researchers to try to minimize the stress response associated with planned surgery through replacing pre-operative fasting by the administration of carbohydrates, whether or not in association with insulin in perfusion. Beneficial results have been described: control of hyperglycaemia, lower consumption of neoglycogenic amino acids and less alteration of plasma immunity (interleukins, TNF). Future studies will evaluate the influence of these measures on plasma immunity, mean hospital stay and morbidity/mortality.
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PMID:[Metabolic response to stress, can we control it?]. 1121 95

The functional characterization of the three distinct alpha2-adrenoceptor (Q2-AR) subtypes was for long hampered by the inavailability of subtype-selective pharmacological probes. Recent studies with gene-targeted mice have revealed that the alpha2A-AR has a major role in the mediation of many prominent effects of subtype non-selective alpha2-AR agonists, i.e. sedation, analgesia, hypothermia, sympatho-inhibition, and reduction of blood pressure. We have now employed several neuropsychopharmacological test models to investigate the effects mediated by the alpha2C-AR subtype and this receptor's potential as a CNS drug target. The studies employed two genetically engineered mouse strains, having either a targeted inactivation of the alpha2C-AR gene (alpha2C-KO) or over-expressing the alpha2C-AR (alpha2C-OE). Lack of alpha2C-AR expression was associated with increased amphetamine-induced locomotor activity, startle reactivity, aggression, and activity in the forced swimming test; prepulse inhibition of the startle reflex was attenuated. Opposite changes were observed in the alpha2C-OE mice. The results suggest that the alpha2C-AR subtype has a distinct inhibitory role in the processing of sensory information and in the control of motor and emotion-related activities in the CNS. It is therefore possible that alpha2C-AR-selective drugs may have therapeutic value in the treatment of various neuropsychiatric disorders.
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PMID:Evaluation of the alpha2C-adrenoceptor as a neuropsychiatric drug target studies in transgenic mouse models. 1135 37

Reflecting its potent inhibition of serotonin (5-HT) reuptake (accompanying paper), S33005 blocked spontaneous tail-flicks induced by parachloroamphetamine in rats. This action was mimicked by the 5-HT reuptake inhibitor, citalopram, and the 5-HT/norepinephrine (NE) reuptake inhibitor, venlafaxine, whereas the preferential NE reuptake inhibitor, reboxetine, was inactive. Consistent with its less potent interaction with NE transporters, higher doses of S33005 attenuated induction of hypothermia by reserpine, an action mimicked by reboxetine and venlafaxine, whereas citalopram was ineffective. In mice, S33005 reduced immobility in forced-swim and tail-suspension procedures. It also inhibited marble-burying behavior and suppressed aggressive behavior between resident and intruder animals. In rats, S33005 generalized to a discriminative stimulus elicited by citalopram and attenuated hypnotic-sedative actions of the alpha2-adrenoceptor agonist, S18616. For these parameters, S33005 was a more potent agent (median, 1.2 mg/kg, s.c.) than venlafaxine, citalopram, reboxetine, or the tricyclic agent, clomipramine. Even at markedly higher doses (40.0-80.0 mg/kg, s.c.), S33005 little affected motor behavior. S33005 (10.0 mg/kg, s.c.) also increased responses in a learned helplessness paradigm in rats, whereas venlafaxine was ineffective. Finally, in a rat chronic mild-stress model, S33005 dose- (2.5-40.0 mg/kg) and time- (2-5 weeks) dependently enhanced sucrose consumption. Venlafaxine was likewise active in this procedure. In conclusion, in line with its inhibition of 5-HT and (less potently) NE reuptake, S33005 is active in a broad range of models suggestive of antidepressant activity. It exerts its actions more potently than venlafaxine and clomipramine, and its overall profile is distinct from those of citalopram and reboxetine.
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PMID:S33005, a novel ligand at both serotonin and norepinephrine transporters: II. Behavioral profile in comparison with venlafaxine, reboxetine, citalopram, and clomipramine. 1145 19

Individual differences in aggressive behaviour have been linked to variability in central serotonergic activity, both in humans and animals. A previous experiment in mice, selectively bred for high or low levels of aggression, showed an up-regulation of postsynaptic serotonin-1A (5-HT(1A)) receptors, both in receptor binding and in mRNA levels, in the aggressive line [Brain Res 736 (1996) 338]. The aim of this experiment was to study whether similar differences in 5-HT(1A) receptors exist in individuals from a random-bred rat strain, varying in aggressiveness. In addition, because little is known about the functional consequences of these receptor differences, a response mediated via postsynaptic 5-HT(1A) receptors (i.e., hypothermia) was studied both in the selection lines of mice and in the randomly bred rats. The difference in receptor binding, as demonstrated in mice previously, could not be shown in rats. However, both in rats and mice, the hypothermic response to the 5-HT(1A) agonist alnespirone was larger in aggressive individuals. So, in the rat strain as well as in the mouse lines, there is, to a greater or lesser extent, an enhanced sensitivity of postsynaptic 5-HT(1A) receptors in aggressive individuals. This could be a compensatory up-regulation induced by a lower basal 5-HT neurotransmission, which is in agreement with the serotonin deficiency hypothesis of aggression.
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PMID:Enhanced sensitivity of postsynaptic serotonin-1A receptors in rats and mice with high trait aggression. 1156 70

Previous reports indicate that the behavioural effects (including anxiolytic-like actions, hypothermia, "serotonergic syndrome," maternal behaviour and aggression and reduction in ambulation) of the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), are completely blocked in lactating rats. The present study compares the behavioural effects of buspirone (1.25, 2.5 and 5.0 mg/kg) and diazepam (0.5, 1.0, 2.0 and 4.0 mg/kg) between ovariectomized and mid-lactating rats. The study was carried out on Wistar female rats under inverted light/dark cycle conditions, by using the burying behaviour paradigm, the elevated plus maze and a general activity test. In both ovariectomized and lactating rats, diazepam produced a dose-dependent reduction in burying behaviour and an increase in the time spent in open arms, responses interpreted as anxiolytic. Buspirone at all doses (1.25, 2.5 and 5.0 mg/kg) produced clear motor impairments in lactating, but not in ovariectomized animals, indicating that the effects of this drug on the anxiety paradigms are unspecific. Diazepam, by contrast, at the highest dose (4.0 mg/kg) similarly inhibited ambulation in both conditions. In the elevated plus maze, control lactating subjects spent more time in the open arms compared with saline-treated ovariectomized subjects, suggesting an anxiolytic-like effect of lactation per se. The present results support the idea that some behavioural actions of drugs acting at the serotonergic system vary between ovariectomized and lactating rats.
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PMID:Diazepam, but not buspirone, induces similar anxiolytic-like actions in lactating and ovariectomized Wistar rats. 1156 45


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