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)

Chronic treatment of rats with imipramine or electroconvulsive shock evokes a significant decrease in binding of [3H]-clonidine to homogenates from the rat brain cerebral cortex. The decrease in binding is accompanied with a functional hyposensitivity of alpha 2-adrenoceptors as measured by attenuation of several central effects of clonidine (e.g. attenuation of clonidine-induced hypothermia, sedation, inhibition of noradrenaline formation). The influence of these antidepressants on alpha 2-adrenoceptors may be of importance in the context of data showing that prolonged treatment with these drugs attenuates the cAMP formation after noradrenergic stimulation, and that the alpha 2-adrenoceptors together with beta-adrenoceptors contribute to the formation of the second messenger. The prolonged administration of imipramine and electroshock, as well as other antidepressant treatments, e.g. administration of the monoamine oxidase inhibitor pargyline or atypical antidepressants such as trazodone, mianserin citalopram, fluoxetine, inhibit the interaction between beta- and-alpha-adrenoceptors (with the alpha 2-subtype playing a major role) and may thus contribute to the phenomenon known as the beta-adrenoceptor down-regulation. The inhibition of the interaction between alpha and beta-adrenoceptors by antidepressants may occur in multiple ways: 1. by lowering the number of beta-adrenoceptors; 2. by lowering the number of alpha 2-receptors (e.g. after imipramine or ETC); 3. by a shift of alpha 2 receptors to a higher affinity state, which represents a desensitized form of the receptor (e.g. decrease in Kd after imipramine or citalopram); 4. by a shift to an antagonist preferring state of the receptor (e.g. after treatment with fluoxetine or trazodone); 5. by a combination of the mentioned above. The functional interaction between alpha and beta adrenoceptors is presumably not dependent upon the integrity of the noradrenergic system, as it not only occurs but also is enhanced in reserpinized or 6OHDA treated rats.
 ...
PMID:The role of alpha 2-adrenoceptors in the mechanism of action of antidepressant drugs. 284 26

2-Amino-2-oxazolines are heterocyclic compounds with interesting pharmacological properties. Several derivatives of this chemical series were studied in psychopharmacological tests. One derivative 4,5-dihydro-5-[methyl(4-phenyl-1-piperazinyl)]-2-oxazolamine (COR 32-24), had an antidepressant profile. Its structure can be compared to trazodone in its phenylpiperazine group and to toloxatone in its oxazoline group. This molecule antagonized reserpine-induced hypothermia and ptosis, oxotremorine-induced hypothermia and high-dose apomorphine-induced hypothermia. It also potentiated yohimbine-induced sublethality and decreased the immobility of forced swimming. It had no monoamine oxidase inhibitory activity. These results suggest a profile close to that of viloxazine and to that of a classic antidepressant.
 ...
PMID:A 2-amino-2-oxazoline derivative as an antidepressant in mice. 326 82

A series of 5-aryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones was prepared and evaluated for potential antidepressant activity. Members of this series were generally prepared by the alkaline ring closures of the corresponding 1-aroylthiosemicarbazides. Several members of this series were potent antagonists of both RO 4-1284-induced hypothermia and reserpine-induced ptosis in mice. In general the more active members of this series were substituted by haloaryl groups at the 5-position of the triazole nucleus and by methyl groups at the 2- and 4-positions. Exchange of the thiocarbonyl group at the 3-position for a carbonyl group resulted in the complete loss of activity. Biochemical evaluation of the more active members of this series indicated that the aforementioned activities were not a consequence of either norepinephrine (NE) uptake or monoamine oxidase inhibition. In an attempt to determine a mechanism of action, one member of this series, compound 22, was selected for further evaluation in an electrophysiological model where it was found to reduce norepinephrine function in the cerebellum as measured by the NE augmentation of GABA inhibition of Purkinje neurons.
 ...
PMID:2,4-Dihydro-3H-1,2,4-triazole-3-thiones as potential antidepressant agents. 337 95

The responses of male and female rats to drugs causing the behavioural syndrome induced by 5-hydroxytryptamine (5-HT) were compared. Preliminary experiments showed that females had largely similar responses to the releaser of 5-HT, p-chloroamphetamine (PCA) and the 5-HT receptor agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) at different stages of the oestrus cycle. The behavioural responses to 5-MeODMT (with and without the monoamine oxidase inhibitor pargyline) or to p-chloroamphetamine were not significantly different to those of males except for tremor after p-chloroamphetamine which was more marked in the females. However, concentrations of p-chloroamphetamine in brain in these animals, when killed immediately after behavioural recording were greater in the females. When rats, pretreated with the monoamine oxidase inhibitor, pargyline, were given the precursor of 5-HT, tryptophan, the females showed substantially greater hypothermia and larger scores for components of the 5-HT syndrome than the males. This sex difference may have been due to the moderately but significantly higher levels of 5-HT (and possibly tryptamine) in brain attained by the female rats, than by similarly-treated males. The results as a whole therefore suggest that the greater behavioural response of female rats to pargyline and tryptophan reflects a greater effect of this treatment on the synthesis of indoleamines than that occurring in males.
 ...
PMID:5-Hydroxytryptamine-mediated behaviour in male and female rats. 374 24

The pharmacological properties of MO-8282 (1,2,3,4-tetrahydro-2-methyl-9H-dibenzo [3,4: 6,7]cyclohepta [1,2-c]pyridine maleate) as an antidepressant were investigated. At doses 10 times less than those of amitriptyline, MO-8282 showed similar potencies in reducing the duration of immobility during forced swimming in rats and in potentiating stereotype induced by L-DOPA. Intermediate doses of MO-8282 reduced the duration of immobility during forced swimming, in mice as well, suppressed muricide behavior of olfactory-bulbectomized rats and antagonized clonidine-induced suppression of exploratory activity in mice. MO-8282 moderately antagonized the ptosis but not the hypothermia induced by reserpine in mice. MO-8282 exhibited weak antagonism against the tremor, lacrimation and diarrhea induced by tremorine, but its activity was milder than that of amitriptyline. The uptake of noradrenaline into rat hypothalamic synaptosomes was inhibited by MO-8282 at concentrations 20 times less than equally effective doses of amitriptyline, but the uptake of dopamine or serotonin was unaffected by MO-8282. A single oral administration of MO-8282 at a dose of 30 mg/kg accelerated noradrenaline turnover, but did not affect dopamine and serotonin turnover in the rat brain. MO-8282 strongly inhibited noradrenaline-, histamine- or adenosine-sensitive adenylate cyclase activity of guinea pig brain. Its mode of action differed from that of imipramine, rather resembling that of mianserin. MO-8282 did not affect monoamine oxidase activity of rat liver. These results suggest that the pharmacological characteristics of MO-8282 are different from those of tricyclic antidepressants and rather similar to those of mianserin, but more potent. The results, therefore, indicate that MO-8282 is possibly a novel antidepressant.
 ...
PMID:[Pharmacological properties of MO-8282, a novel antidepressant]. 379 61

The pharmacological properties of two selective inhibitors of monoamine oxidase (MAO) type B, L-deprenyl and MDL 72145 [(E)-2-(3,4-dimethoxyphenyl)-3-fluoroallylamine, HCl], have been investigated in rats and mice in relation to their effects on MAO. Selective inhibition of MAO B achieved following 18 h pretreatment with L-deprenyl and/or MDL 72145 did not per se lead to prominent pharmacological activity; no effects were seen in the mouse "Behavioural Despair" test, hypothermia induced by reserpine in mice was neither prevented nor reversed and there was no change in the cardiovascular responsiveness of the pithed rat to tyramine, noradrenaline or stimulation of the spinal sympathetic outflow. L-Deprenyl differed from MDL 72145 in that short term treatment with this drug caused positive effects in the "Behavioural Despair" test, reversal of reserpine hypothermia, indirect sympathomimetic stimulation of blood pressure and heart rate in the pithed rat and ipsilateral rotation in rats with unilateral nigro-striatal lesions. Qualitatively similar effects were seen with dexamphetamine. The marked difference between the pharmacological effects of MDL 72145 and L-deprenyl despite equivalent inhibition of MAO B suggests that many of the pharmacological actions of L-deprenyl result from its amphetamine-like sympathomimetic properties. MDL 72145 can, therefore, be considered a more reliable tool with which to explore the functional importance of MAO B inhibition in experimental animals and man.
 ...
PMID:The functional consequences of inhibition of monoamine oxidase type B: comparison of the pharmacological properties of L-deprenyl and MDL 72145. 393 59

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.
 ...
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.
 ...
PMID:Role of noradrenaline and 5-hydroxytryptamine in tetrahydronaphthylamine-induced temperature changes in the rat. 425 29

1. Ouabain given by intracerebroventricular injection to mice in small doses (0.1-0.4 mug) produced a dose related depression of central nervous activity, characterized by a reduction in spontaneous locomotor activity, hypothermia, catalepsy and ptosis, lowered body posture and lack of response to external stimuli. Doses above 0.4 mug were excitatory, convulsant and lethal.2. The depressant effects could be antagonized by (+)-amphetamine, desmethylimipramine, dibutyryl cyclic 3'5'-adenosine monophosphate and caffeine.3. The MAO inhibitor nialamide produced only a small antagonism of ouabain, resulting in a greater rate of recovery from the depressant effects of ouabain.4. The depressant effects were associated with a marked elevation of whole-brain dopamine levels with little change in noradrenaline or 5-hydroxytryptamine.5. The dopamine-beta-hydroxylase inhibitor sodium diethyldithiocarbamate, administered by intracerebroventricular injection, produced effects qualitatively similar to those seen after ouabain.6. An interference with central transmitter function is postulated as a possible mode of action of intracerebroventricularly injected ouabain.
 ...
PMID:Pharmacological properties of centrally administered ouabain and their modification by other drugs. 432 23

1. In cats, the effects of intraperitoneal injections of four monoamine oxidase (MAO) inhibitors, tranylcypromine, pheniprazine, pargyline, and nialamide, were examined on rectal temperature and on the hypothermia during anaesthesia produced by a 2 hr period of halothane inhalation.2. A 2 hr period of halothane inhalation produced a steady fall in temperature amounting to between 2 degrees and 3.5 degrees C. After discontinuation of halothane inhalation, temperature quickly returned to the pre-anaesthetic level but no pyrexia developed. A peculiar stiffness of the leg muscles occurred in several experiments either at the beginning of the inhalation or after its discontinuation.3. An injection of tranylcypromine (5 mg/kg) caused a rise in rectal temperature and prevented the hypothermia of halothane anaesthesia. This effect lasted for at least 4 hr; 20 hr after the injection, halothane again caused hypothermia.4. An injection of pheniprazine (10 mg/kg) usually caused a small rise in temperature which was not sustained. Pheniprazine not only prevented the hypothermia of halothane anaesthesia during the subsequent 20 hr, but during the first few hours after the injection halothane inhalation actually produced a steep rise in temperature.5. An injection of pargyline (50 mg/kg) had no effect on temperature but the hypothermia due to halothane inhalation was prevented 1 hr after the injection and attenuated after 20 hr. Injection of 200 mg/kg caused a steady rise in temperature which was accelerated when halothane was administered 1 hr later.6. An injection of nialamide (10, 25 or 50 mg/kg) had no immediate effect on temperature, but pyrexia developed overnight after the two larger doses. The effect on the hypothermia due to halothane inhalation was greater 20 hr after the injection than it was after 1 to 2 hr. Twenty hours after injection of the two larger doses, halothane no longer produced hypothermia but caused a lethal rise in temperature either during or after its inhalation.7. In rabbits, the effect on temperature of halothane inhalation varied. Either temperature rose slightly or it fell, but not as much as in cats. In one rabbit in which the inhalation had produced a transient rise, pyrexia developed 40 min after discontinuation of halothane.
 ...
PMID:Effects of monoamine oxidase inhibitors on the hypothermia produced in cats by halothane. 439 Jun 71


<< Previous 1 2 3 4 5 6 Next >>