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 2-(4-(4-(2-pyrimidinyl)-1-piperazinyl)-butyl)-1,2-benzoisothiazol- 3(2H)one-1, 1-dioxide hydrochloride (isapirone, TVX Q 7821), a putative 5-HT1 receptor antagonist, has been studied on various models of 5-HT receptor sub-type function. In mice TVX Q 7821 produced a dose-dependent inhibition of the hypothermia induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) with an ED50 of 5.3 mg/kg suggesting that TVX Q 7821 was an antagonist of the presynaptic (possibly somato-dendritic) 5-HT1A receptor. TVX Q 7821 did not alter the locomotor response to the suggested 5-HT1B agonist RU 24969. The rate of mouse brain 5-HT synthesis was accelerated by TVX Q 7821 (10 mg/kg). 5-HT2 receptor-mediated head twitch behaviour induced by precursor loading with 5-HTP was unaffected by TVX Q 7821 (10 mg/kg) pretreatment 75 min earlier, but the head-twitch induced by the agonist 5-methoxy-N,N-dimethyltryptamine was enhanced by prior treatment with TVX Q 7821. In rats the hypothermia induced by 8-OH-DPAT was partially antagonised by TVX Q 7821 while the behavioural "serotonin syndrome" induced by 8-OH-DPAT (a possible post-synaptic 5-HT1B-mediated effect) was unaffected by TVX Q 7821 as was the locomotion induced by RU 24969. The data suggest that TVX Q 7821 is a good presynaptic 5-HT1A antagonist in mice, as indicated by the 8-OH-DPAT-induced hypothermia and 5-HT synthesis rate studies. It did not antagonise 5-HT1B-mediated behaviour in mice or rats and appeared to have an antagonist action at pre- but not post-synaptic 5-HT1A receptors in rats.
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PMID:The effects of a 5-HT1 receptor ligand isapirone (TVX Q 7821) on 5-HT synthesis and the behavioural effects of 5-HT agonists in mice and rats. 294 17

The acute and chronic effects of capsaicin (s.c.) on the monoamines in the preoptic region + hypothalamus (RPO-H), spinal cord, substantia nigra and striatum were studied. Levels of DOPA, DA, DOPAC, HVA, 3-MT, NA, Trp, 5-HTP, 5-HT and 5-HIAA were determined by means of liquid chromatography (HPLC-EC). In response to acute capsaicin treatment, the levels of DA, DOPAC and DA synthesis rate (DOPA formation) were increased in a dose-dependent manner in the RPO-H and spinal cord. The disappearance rate of NA was accelerated in both regions. In substantia nigra, increased DOPAC levels were found whereas the levels of 3-MT were decreased in striatum after acute capsaicin treatment. Only minor changes on the levels of 5-HT and 5-HIAA in the regions studied were noted. Neonatal or adult capsaicin treatment failed to affect the levels of NA, DA and 5-HT (measured two months or five weeks after injection, respectively) in the regions studied. A capsaicin injection to rats pretreated with the drug as adults did not affect either the monoamines in the RPO-H and spinal cord or the body temperature. In contrast, in rats pretreated with capsaicin as neonates, a second injection of the drug to adult animals elicited hypothermia and changes in monoamines similar to those observed in naive animals.
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PMID:Effects of capsaicin on central monoaminergic mechanisms in the rat. 302 47

The pharmacological actions of N-(2,6-dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride hemihydrate (SUN 1165), a new antiarrhythmic agent, on the central nervous system were studied in various experimental animals as compared with those of disopyramide, mexiletine and lidocaine, and the following results were obtained. 1. Acute toxicity of SUN 1165 in mice was similar to that of mexiletine, and twice as potent as compared with that of disopyramide and lidocaine. Main acute toxic symptoms of SUN 1165 were muscle relaxation, ataxia, clonic convulsions, tremor and a decrease in spontaneous activity in mice, rats and rabbits. In addition to these symptoms, vomiting in dogs was observed. These toxic symptoms were similar to those of lidocaine. In the case of disopyramide, ataxia, tremor and a decrease in spontaneous activity were observed in mice and rats. On the other hand, mexiletine caused central nervous excitatory symptoms, that is, tremor, Straub tail, clonic convulsions, jumping, running and opisthotonus in mice and rats, and vomiting in dogs. 2. SUN 1165 even at large doses (50-100 mg/kg p.o.) exerted no significant effects on the following changes: hexobarbital-induced induced hypnosis, oxotremorine-induced tremor, apomorphine-induced hypothermia, reserpine-induced ptosis and hypothermia, 5-hydroxytryptophan syndrome and fighting behavior in mice, and conditioned avoidance response in rats. 3. An ineffective dose of SUN 1165 (12.5 mg/kg p.o.) on spontaneous locomotor activity was lower than of disopyramide and lidocaine, however, higher than that of mexiletine. 4. SUN 1165 at large doses showed antagonistic action on toxic extensor seizures induced by maximal electroshock, picrotoxin, or strychnine in mice, but anticonvulsive effects of SUN 1165 were less potent than those of mexiletine and lidocaine. SUN 1165 had no effect on clonic convulsions induced by pentetrazol and pictrotoxin in mice, while both mexiletine and lidocaine prolonged the duration of clonic convulsions. 5. The muscle relaxant effect of SUN 1165 (50%-toxic dose, TD50 = 30 mg/kg p.o.) was more marked than that of lidocaine (TD50 = 92 mg/kg p.o.) on traction test in mice. However, effect of SUN 1165 (TD50 = 62 mg/kg p.o.) on motor incoordination was similar to that of disopyramide, mexiletine and lidocaine on the rotarod test in mice. 6. The analgesic effect of SUN 1165 was as weak as that of disopyramide, mexiletine and lidocaine on chemically and mechanically-induced pain response in mice.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:General pharmacological studies on N-(2,6-dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride hemihydrate. 1st communication: effect on the central nervous system. 319 80

The central action of 2,3,3a,4,5,6-hexahydro-8-methyl-1H-pyrazino[3,2,1-j,k]carbazole hydrochloride (pirlindole, PIR) in mice and rats was studied. PIR inhibited the 3H-5-hydroxytryptamine (5-HT) uptake in the rat cerebral cortex, not affecting the uptake of 3H-noradrenaline. PIR counteracted the reserpine ptosis but did not alter the apomorphine hypothermia. It enhanced the L-dopa effect on the locomotor activity and the L-5-hydroxytryptophan (L-5-HTP)-induced head twitch reaction in mice. PIR also facilitated the effect of L-dopa and L-5-HTP on the hind limb flexor reflex of the spinal rat. The clonidine sedation (but not hypothermia) was attenuated by PIR. PIR given repeatedly for 18 days increased the binding of 3H-prazosin in the brain cortex (decreasing the KD value), but did not affect the binding of 3H-dihydroalprenolol. The obtained results indicate that PIR inhibits the 5-HT uptake, displays characteristics of a monoamineoxidase inhibitor and, when given repeatedly, increases the binding to alpha 1-adrenoceptors in the cerebral cortex.
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PMID:Central action of the antidepressant drug pirlindole. 349 Aug 54

The various pineal gland tryptophan metabolites were administered to male rats intraperitoneally (100 micrograms/kg) and rectal temperatures were recorded. Of the compounds tested, hydroxytryptophan, N-acetylserotonin, hydroxytryptophol, and their corresponding methoxyindoles all caused a marked hypothermia, indicating that several indolic products may be involved in thermoregulation. Although the brain penetration of indoles is poor, a central site of action would be most likely, although peripheral actions cannot be excluded. The mechanism of induction of hypothermia may involve peptides, the pituitary-thyroid axis, the adrenal gland, or a combination of these. These results may suggest that the pineal gland integrates environmental cues to act in concert with physiological thermostats in the fine tuning of thermoregulation.
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PMID:Both hydroxy- and methoxyindoles modify basal temperature in the rat. 355 85

A potential antidepressant activity and an antiserotonin action of Org 8282, delta (13b, 4a), 4a-carba-mianserin, was studied in mice and rats. Org 8282 did not affect the reserpine-induced hypothermia, hypoactivity and ptosis, did not modify the apomorphine-induced hypothermia and the TRH-induced hyperthermia in mice, did not change the motor stimulation and stereotypy produced by amphetamine. It was inactive in the behavioral despair test in rats and mice. On the other hand, Org 8282 inhibited the head twitch reaction after 5-HTP in mice, the tryptamine-induced clonic convulsions of forepaws in rats, the hyperthermia produced by fenfluramine and m-CPP in rats kept at a high ambient temperature, and the quipazine-induced stimulation of the flexor reflex activity in the spinal rat. These results indicate that Org 8282 is inactive in tests commonly applied for assessment of antidepressant action but--like mianserin--it exerts an antiserotonin activity.
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PMID:The lack of antidepressant properties and a potent central antiserotonin activity of Org 8282. 377 30

Carbamazepine (CBZ) was studied in mice and rats with regard to its antidepressant activity. CBZ did not counteract hypothermia and ptosis induced by reserpine, hypothermia evoked by apomorphine, or sedation and hypothermia induced by clonidine. CBZ shortened the immobility time in the behavioral despair test in rats (but not in mice). It attenuated hyperactivity evoked by d-amphetamine, not affecting stereotypy induced by that drug. CBZ inhibited head twitches evoked by 5-HTP, as well as the hind limb flexor reflex of the spinal rat, having no effect on its stimulation by noradrenaline and 5-hydroxytryptamine agonists. CBZ administered repeatedly did not enhance clonidine aggressiveness or d-amphetamine locomotor hyperactivity, acting differently than many antidepressant drugs. The obtained results indicate that CBZ is not similar in its action to typical and many atypical antidepressants.
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PMID:The central action of carbamazepine as a potential antidepressant drug. 404 Oct 37

Pirenperone, an antagonist of 5-HT2 but not 5-HT1 receptors, has been studied for its central antiserotonergic and antidopaminergic activity. Pirenperone (0.00525-0.1 mg/kg) antagonized dose-dependently stimulation of the hind limb flexor reflex in spinal rats induced by LSD, quipazine or fenfluramine, and hyperthermia induced by serotonin (5-hydroxytryptamine; 5-HT)-like drugs (1-5-hydroxytryptophan, fenfluramine, p-chloroamphetamine, 1-/m-chlorophenyl/-piperazine, quipazine) in heat-adapted rats. Pirenperone also counteracted tryptamine-induced convulsions in rats (ID50 = 0.87 mg/kg); however, this action was weaker than that of metergoline (ID50 = 0.22 mg/kg). Pirenperone (0.1-1.6 mg/kg) produced sedation in mice and rats, and-in doses of 0.4-6.4 mg/kg-catalepsy in rats. Given in doses ranging from 0.1 to 1.6 mg/kg, pirenperone antagonized d-amphetamine-induced locomotor hyperactivity in mice and rats, the hyperactivity induced by apomorphine in rats, apomorphine- or d-amphetamine-induced stereotypy in rats and stimulation of the hind limb flexor reflex induced by the alpha-adrenoceptor agonist-clonidine. Pirenperone (6.4 mg/kg) significantly attenuated apomorphine (1 mg/kg)-induced hypothermia in mice. The results obtained indicate that pirenperone may be regarded as a relatively specific antagonist of the 5-HT2 receptor only when it is employed in very low doses (less than 0.1 mg/kg). Used in higher doses (greater than 0.1 mg/kg), it behaves like a typical neuroleptic, i.e. like a dopamine antagonist with antiserotonergic, antitryptaminergic and antiadrenergic properties.
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PMID:Central antiserotonergic and antidopaminergic action of pirenperone, a putative 5-HT2 receptor antagonist. 404 12

The new substance (+/-)8-chloro-1,2,3,4,10,10a-hexahydro-2-methyl-4a,10-(iminoethano )-4aH -[1]benzopyrano[3,2-c]pyridin-12-one (4a alpha,10 alpha,10a alpha) (lortalamine, LM 1404) is compared with imipramine in a series of pharmacological and biological tests. Lortalamine antagonises in a dose-related manner reserpine-induced ptosis and hypothermia, and is far more potent than imipramine in this regard. The compound potentiates yohimbine toxicity in mice and, in the anesthetized dog, diminishes the tyramine pressure response while increasing the response to norepinephrine. These results would indicate the capacity for lortalamine to act as a norepinephrine uptake inhibitor, and indeed, lortalamine is more potent than imipramine in inhibiting norepinephrine uptake by rat brain cortex slices. Lortalamine does not inhibit serotonin uptake by rat midbrain slices and neither interferes with 5-hydroxytryptophan and p-chloroamphetamine in mice. The interference with the dopaminergic system seems to be slight or even negligible, since the compound does not interfere with apomorphine or amphetamine in mice; moreover, dopaminergic uptake by rat striatum synaptosomes is inhibited only at very high concentrations. Lortalamine does not modify norepinephrine release, MAO activity nor behaviour of mice. Contrary to tricyclic antidepressants, lortalamine is devoid of anticholinergic and antihistaminic properties. The vegetative and cardiovascular effects as studied in the anesthetized dog are either absent or very slight. In particular, heart conduction is far less impaired in comparison to imipramine, which correlates with the absence of local anesthetic properties of the product.
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PMID:Pharmacology of lortalamine, a new potent non-tricyclic antidepressant. 409 69

1. Intraperitoneal administration of graded doses of tetrahydronaphthylamine (THN) to rats caused a dose dependent decrease in body temperature.2. Intracisternal injection of graded doses of THN induced hypothermia, and implantation of crystalline THN rostral to the medial preoptic area and caudal to the striatum, caused hyperthermia.3. Pretreatment of the rats with a MAO inhibitor changed the hypothermia into hyperthermia.4. Intraperitoneal injection of 5-hydroxytryptophan caused a hypothermia which could be reversed into hyperthermia when the rats were pretreated with a MAO inhibitor.5. Pretreatment with parachlorophenylalanine enhanced the THN-induced hypothermia.6. Depletion of brain monoamines by Ro-4-1284 in combination with an inhibition of the biosynthesis of noradrenaline (diethyldithiocarbamate) changed the THN-induced hypothermia into hyperthermia.7. It is concluded that THN affects body temperature in rats by two central mechanisms, viz. a decrease mediated by noradrenaline, probably in the hypothalamus, and an increase which might be mediated by 5-hydroxytryptamine rostral to the medial preoptic area.
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PMID:Role of noradrenaline and 5-hydroxytryptamine in tetrahydronaphthylamine-induced temperature changes in the rat. 425 29


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