Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. At an ambient temperature of 20 degrees C, intraventricular injection of noradrenaline in the mouse resulted in hypothermia accompanied by a fall in metabolic rate and by cutaneous vasodilatation. Subcutaneous injection of noradrenaline resulted in hyperthermia with raised metabolic rate and cutaneous vasodilatation.2. The hypothermia and fall in oxygen consumption rate following intraventricular noradrenaline were prevented by pre-treatment with subcutaneous propranolol, while the cutaneous vasodilatation was un-affected. However, the effects of subcutaneously injected noradrenaline were completely abolished by subcutaneous propranolol. Intraventricular propranolol did not modify the hypothermic effect of intraventricular noradrenaline.3. The direction of the effect on body temperature of intraventricular noradrenaline was dependent upon ambient temperature; hypothermia occurring at low (15 degrees C) and hyperthermia at high (36 degrees C) ambient temperatures. However, when the possibility of any peripheral action of noradrenaline escaping into the systemic circulation was prevented by prior subcutaneous injection of propranolol, significant hypothermia could be detected at temperatures as high as 32 degrees C.4. The possibility that the effects of intraventricular noradrenaline could be due to complete abolition of central temperature regulation was further excluded by the occurrence of thermal salivation in all animals during experiments performed at 36 degrees C.5. It is suggested that, in the mouse, the hypothermic actions of intraventricular noradrenaline are due to a central effect, while its hyperthermic effects at high ambient temperature are due to escape of noradrenaline into the peripheral circulation. The hypothermia could be the result of selective activation of central heat loss mechanisms.6. Intraventricular noradrenaline was without effect on brain plasma-space although exposure to 100% oxygen caused a detectable fall.
 ...
PMID:thermoregulatory effects of intraventricular injection of noradrenaline in the mouse and the influence of ambient temperature. 504 35

1. The concentrations of adrenaline and noradrenaline in the adrenal vein and the adrenal gland of the cat were studied in response to different stimuli leading to increased catecholamine (CA) secretion.2. Haemorrhage and hypoglycaemia, but not acute exposure to cold or intravenous administration of cocaine, induced considerable increases in total catecholamine secretion.3. The ratio of the concentration of adrenaline to noradrenaline in adrenal vein plasma during the control period was higher than the ratio in the adrenal gland itself.4. Haemorrhage increased noradrenaline secretion considerably more than adrenaline secretion so that the ratio of the concentration of adrenaline to noradrenaline in adrenal vein plasma was significantly lower than in the adrenal gland itself.5. Hypoglycaemia induced by insulin increased catecholamine secretion, with the adrenaline to noradrenaline ratio significantly higher than in the adrenal gland itself.6. Hypothermia resulted in a fall of the initial high ratio of adrenaline to noradrenaline, to a value similar to that in the adrenal gland.7. Neither cocaine nor changes in adrenal plasma flow affected the adrenaline to noradrenaline ratio in adrenal vein blood.8. It is concluded that preferential release from the adrenal gland of either adrenaline or noradrenaline is possible in vivo in response to different stimuli.
 ...
PMID:Preferential secretion of adrenaline or noradrenaline by the cat adrenal in vivo in response to different stimuli. 515 27

The hypothermia observed in rats kept in a cold environment after the intracisternal administration of 6-hydroxydopamine was enhanced by desipramine. Since pretreatment with 6-hydroxydopamine virtually eliminated the temperature fall in response to a subsequent dose of 6-hydroxydopamine, brain catecholamines were implicated in the response. Preferential reduction of brain noradrenaline antagonized the hypothermia after 6-hydroxydopamine in desipramine-treated rats to a greater extent than did the preferential reduction of dopamine. The results indicate the importance of noradrenergic fibres in this hypothermic response, but do not exclude an involvement of brain dopaminergic pathways.
 ...
PMID:Effect of central catecholamine alterations on the hypothermic response to 6-hydroxydopamine in desipramine treated rats. 515 28

1. In unanaesthetized mice, weighing 20-30 g, the effect of (+)-amphetamine sulphate and p-hydroxyamphetamine hydrobromide on rectal temperature was examined. The drugs were injected intraperitoneally or into the cerebral ventricles.2. Amphetamine produced hypothermia when injected intraperitoneally in doses of 1-5 mg/kg and intraventricularly in doses of 0.5 to 25 mug. Injections of larger doses-10 mg/kg intraperitoneally and 400 mug intraventricularly-resulted in hyperthermia followed by hypothermia.3. Hydroxyamphetamine produced hypothermia only when given by the intra-ventricular route; the effect was obtained with 0.5 to 25 mug. An intraventricular injection of 200 mug resulted in hyperthermia followed by hypothermia. When injected intraperitoneally the sole effect on temperature was hyperthermia, and this response was obtained with 5 and 10 mg/kg.4. Hydroxyamphetamine injected intraperitoneally or intraventricularly in doses which produced hyperthermia reduced the noradrenaline but not the dopamine content of the brain. When injected intraventricularly in smaller doses which produced hypothermia no reduction in the noradrenaline content of the brain was obtained.5. The hypothermia is attributed to an action on the anterior hypothalamus, and the possibility is discussed that it is brought about indirectly by the release of noradrenaline. The hyperthermia on the other hand is probably a peripheral effect.
 ...
PMID:A cntral site for the hypothermic effects of (+)-amphetamine sulphate and p-hydroxyamphetamine hydrobromide in mice. 549 94

1. Rats which had been pretreated with intraventricular injections of 6-hydroxydopamine (6-OHDA) to cause a selective depletion of brain noradrenaline (NA) to 20.7% of control brain NA and brain dopamine (DA) to 34.6% of control brain DA retained an unimpaired ability to regulate their body temperatures on exposure to heat or cold. This is discussed in relation to the possible role of brain NA in the central control of body temperature.2. Intraventricular injections of 6-OHDA in normal rats at room temperature caused an acute, dose dependent hypothermia of up to 4.5 degrees C which lasted for 4-5 hours. Depletion of brain NA and DA by prior treatment with 6-OHDA markedly reduced the hypothermic response to a subsequent dose of 6-OHDA. Selective depletion of brain NA without affecting brain DA did not reduce the response to 6-OHDA. The acute hypothermic response to 6-OHDA, may therefore, be related to a release of DA in the brain.
 ...
PMID:Central effects of 6-hydroxydopamine on the body temperature of the rat. 549 72

1. Noradrenaline given directly into the lateral cerebral ventricles induced hypothermia in mice. This hypothermia was antagonized and eventually reversed to a hyperthermia by imipramine-like antidepressant drugs.2. The mechanism of action involved in this effect of antidepressant drugs has been studied using nortriptyline as a typical representative of antidepressant drugs.3. Nortriptyline pretreatment did not modify either the uptake, subcellular distribution, or the metabolism of (3)H-noradrenaline injected into the lateral cerebral ventricles.4. Nortriptyline had the same order of activity in reversing the hypothermia produced by the intraventricular injection of noradrenaline irrespective of whether it was given directly into the lateral cerebral ventricles or subcutaneously.5. Noradrenaline given subcutaneously caused hyperthermia in mice which antagonized and reversed the hypothermia induced by noradrenaline given directly into the lateral ventricles.6. The antagonism by both noradrenaline given subcutaneously and nortriptyline was reduced to the same degree by alpha- and beta-adrenoceptive receptor blocking agents.7. Nortriptyline, at dose levels required to antagonize and reverse the hypothermia induced by intraventricular injections of noradrenaline, potentiated the hyperthermia caused by noradrenaline given subcutaneously in conscious mice and the pressor responses to noradrenaline given either intravenously or into the lateral ventricles in anaesthetized mice.8. It is suggested that imipramine-like antidepressant drugs antagonize the hypothermia produced by intraventricular injections of noradrenaline by potentiating the hyperthermic effects of that part of the centrally administered noradrenaline that passes to the periphery rather than a direct central antagonism of the effects of noradrenaline.
 ...
PMID:The reversal of the central effects of noradrenaline by antidepressant drugs in mice. 567 4

1. The hypothesis of Roberts & Broadley (1965) that noradnamine formation in the brain is responsible for endogenous depression has been investigated in mice.2. Injections of noradnamine given directly into the lateral ventricles caused convulsions and profound hypothermia, but were without effect if given subcutaneously.3. The hypothermia, but not the convulsions, induced by noradnamine was reversed by imipramine-like antidepressant drugs given before or after the injection of noradnamine. The convulsions but not the hypothermia were abolished by phenobarbitone.4. Increasing doses of nortriptyline produced a parallel shift of the hypothermic log dose-response curve for intraventricular injections of noradnamine to the right.5 The minimal effective dose of nortriptyline required to reverse noradnamine hypothermia was the same whether the nortriptyline was injected directly into the lateral ventricle or subcutaneously.6. No evidence was found to substantiate the claim that reserpine hypothermia is mediated by noradnamine formation in the brain.7. Intraventricular, but not intraperitoneal, injection of noradnamine caused a depletion of brain noradrenaline and an increase in brain 5-hydroxytryptamine. These changes did not result from the convulsive activity and were not modified by pretreatment with nortriptyline. No effect on heart noradrenaline levels was recorded.8. Noradrenaline, given subcutaneously, also antagonized the hypothermic response to noradnamine.9. The reversal of noradnamine hypothermia by both noradrenaline given subcutaneously and nortriptyline was blocked by alpha and beta-adrenoceptive receptor blocking agents.10. It is considered that the mode of action of the antagonism of noradnamine hypothermia by imipramine-like antidepressant drugs is a peripheral and not a central mechanism and probably results from a potentiation of the effects of circulating noradrenaline released by noradnamine.
 ...
PMID:The interactions of noradnamine and imipramine-like antidepressant drugs. 576 31

1. Changes in temperature were determined following injection of noradrenaline, adrenaline, isoprenaline, dopamine and 5-hydroxytryptamine (5-HT) into the cerebral ventricles of the conscious mouse.2. Noradrenaline (1-20 mug) and dopamine (10-160 mug) caused falls in body temperature. Adrenaline (1-20 mug) caused a slight and transient rise in body temperature followed by a fall. Isoprenaline (5-20 mug) caused a rise in body temperature, hypothermia only occurring after very high doses (200 mug) of this catecholamine.3. alpha- and beta-adrenergic blocking agents, phentolamine (> 2 mug) and propranolol (> 5 mug) respectively, caused falls in body temperature when injected into the cerebral ventricles of the mouse.4. Specific drug antagonism studies were limited owing to the intrinsic effects of the alpha- and beta-adrenergic blocking agents. However, some evidence was obtained to indicate that noradrenaline mediated its effects through a central alpha-type adrenergic receptor.5. 5-HT (10-160 mug) caused a fall in body temperature. The action of this indoleamine and the catecholamines in regard to thermoregulatory function is discussed.
 ...
PMID:Temperature changes produced by the injection of catecholamines and 5-hydroxytryptamine into the cerebral ventricles of the conscious mouse. 605 3

The N-desmethyl metabolites of imipramine and amitriptyline possess antidepressant activity in their own right. To test whether this is also true of desmethylclomipramine, studies have been carried out on appropriate models. Desmethylclomipramine was shown to be present in plasma in higher concentrations than the parent compound, to be strongly active in reversing or suppressing reserpine-induced hypothermia, to possess anticholinergic activity on gastrointestinal smooth muscle, inhibiting motility and antagonizing muscarinic receptors, though to a lesser extent than clomipramine. It is also a more potent inhibitor of noradrenaline and dopamine uptake than clomipramine is, though less potent in inhibiting 5-hydroxytryptamine uptake. The metabolite has antidepressant activity of its own, probably associated with its monoamine uptake inhibitory properties, and doubtless makes an important contribution to the efficacy of treatment of depression with clomipramine; for this reason plasma levels of the metabolite as well as those of the parent compound should be taken into account.
 ...
PMID:Some pharmacological aspects of desmethylclomipramine. 610 7

General pharmacological properties of 4'-fluoro-4-[4-(2-thioxo-1-benzimidazolinyl) piperidino] butyrophenone (timiperone), a new neuroleptic drug, were compared with those of haloperidol. 1. Central nervous system: In behavioral observation, timiperone showed a typical neuroleptic profile at doses of 0.1 mg/kg p.o. and more (mice). The drug produced a moderate hypothermia at 10 mg/kg p.o. (rabbits), a mild increase in pain threshold at 3 mg/kg p.o. (mice and rats) and a slowing of cortical EEG at 1 mg/kg i.v. (cats). ED50 values of drug for the potentiation of ether and alcohol anesthesia were 0.34 and 0.22 mg/kg p.o., respectively (mice). Timiperone ahd neither an anticonvulsant activity at 30 mg/kg p.o. (mice) nor an effect on the spinal reflex at 1 mg/kg i.v. (cats). These effects of timiperone on the central nervous system were almost similar to those of haloperidol. 2. Respiratory and cardiovascular system: At dose of 0.03 mg/kg i.v. and more, timiperone produced transient increases in respiratory rate and regional arterial blood flow which were accompanied by a fall in blood pressure (dogs). Haloperidol had qualitatively similar effect, but was weaker than timiperone. Both drugs at high concentration (3X10-6 g/ml) exerted negative inotropic and chronotropic effect in isolated atrial preparations (guinea-pigs), and non-competitively antagonized the positive chronotropic action of isoprenaline. Atropine (2.5X10-7 g/ml) failed to modify the chronotropic action of timiperone (3X10-6 g/ml). 3. Autonomic nervous system: Timiperone at 0.1 mg/kg p.o. and haloperidol at 0.3 mg/kg p.o. induced a moderate miosis (rabbits) and antagonized blood responses to noradrenaline and acetylcholine (dogs). Both drugs at 1 mg/kg i.v. had no ganglion-blocking activity (cats). 4. Smooth muscle: In isolated guinea-pig ileum and vas deferens, timiperone and haloperidol (10-5 g/ml) antagonized the contractile responses of the muscles to various spasmogens, Both drugs at approximately 10-6 g/ml decreased spontaneous motility of the isolated rat uterus and inhibited the gastric secretion at 1 mg/kg i.p. (rats). At high doses, both drugs inhibited the gastrointestinal propulsion (mice), motility (dogs) and gastric emptying rate (rats), and had no damaging effect on the gastric mucosa (rats). 5. Skeletal muscle: At 0.1 mg/kg i.v., timiperone and haloperidol slightly enhanced twitch response of the anterior tibial muscle to electrical stimulation (rabbits). 6. Urine volume and urinary electrolytes: Timiperone and haloperidol showed a diuretic effect at 3 mg/kg p.o. whereas they inhibited urine output and electrolytes excretion at 30 mg/kg p.o. (rats).
 ...
PMID:Pharmacological studies on timiperone, a new neuroleptic drug Part II: General pharmacological properties. 611 34


<< Previous 1 2 3 4 5 6 7 8 9 10