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 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.
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PMID:[Pharmacological properties of MO-8282, a novel antidepressant]. 379 61

The effects of beta-endorphin, MIF-I, and alpha-MSH on d-amphetamine- a CPZ-induced hypothermias in rats kept at 4 degrees C were tested in three experimental groups: (a) intact; (b) rats with lesions of the olfactory tubercle; and (c) rats in which the link between the DA mesolimbic pathway and the striatum was disconnected. All drugs tested alone (except MIF-I) caused significant hypothermia. Pretreatment with CPZ, MIF-I, and alpha-MSH potentiated d-amphetamine-induced hypothermia in intact rats. Pretreatment with alpha-MSH potentiated CPZ-induced hypothermia. beta-Endorphin partially blocked d-amphetamine-induced hypothermia, but did not interact with CPZ, MIF-I, or alpha-MSH. All potentiations were either reduced or disappeared in the incisioned rats. CPZ and alpha-MSH caused hypothermia in olfactory tubercle-lesioned rats. The results indicate that: (a) the DA mesolimbic pathway is involved in the hypothermic response of all drugs tested; (b) an intact feedback loop is required for the potentiation of the hypothermic response of CPZ on d-amphetamine, MIF-I on d-amphetamine, and alpha-MSH on d-amphetamine and CPZ; (c) beta-endorphin acts as a partial blocker of d-amphetamine; MIF-I is a weak potentiator of d-amphetamine, alpha-MSH acts as a negative modulator of the DA system, most probably in the striatum.
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PMID:Modification of d-amphetamine- or chlorpromazine-induced hypothermia by beta-endorphin, MIF-I, and alpha-MSH: mediation by the dopaminergic system. 612 51

Following the administration of two gamma-aminobutyric acid-(GABA) elevating drugs, namely aminooxyacetic acid (AOAA) and valproic acid (VPA), in rats, the relationship between the magnitude and the time course of increases in GABA levels of 11 brain regions and a number of pharmacological effects was studied. AOAA (30 mg/kg i.p.) caused significant GABA increases in all brain areas but the degree and time course of these increases showed considerable variation from region to region. The most marked effects were seen in the olfactory bulb, frontal cortex and hippocampus, in which maximum GABA elevations of 100-200% were reached 4-6 hr after AOAA injection. In all the other regions studied (corpus striatum, thalamus, hypothalamus, superior and inferior colliculus, substantia nigra, pons, medulla, cerebellum), increases in GABA were less marked and, at least in part, maximum increases (30-60% over control) were already reached by 1-2 hr. In contrast to AOAA, VPA (200 mg/kg i.p.) produced significant increases in GABA levels only in the cortex, olfactory bulb, corpus striatum, hypothalamus and cerebellum, maximum effects (15-35%) being already reached 5-30 min after VPA administration. As regards pharmacological effects, AOAA caused marked hypothermia, which was maximal by 1 hr and could be reversed by increasing ambient temperature, whereas effects of VPA on body temperature were only moderate. On the other hand, both drugs exerted an almost equal, pronounced antinociceptive effect in the hot plate test. Anticonvulsant efficacy was evaluated in three seizure models, namely the maximal (tonic extension) electroconvulsive threshold, and seizures induced by pentylenetetrazol and 3-mercaptopropionic acid. Anticonvulsant effects of AOAA against electroshock and pentylenetetrazol could only be determined 1 hr after injection, at which time AOAA was inactive against 3-mercaptopropionic acid-induced seizures. VPA proved to be clearly superior to AOAA in both anticonvulsant potency and duration of action. The marked differences in functional effects between VPA and AOAA could not be related to their differential effects on GABA levels in discrete brain regions. The data thus suggest that measurement of total GABA in brain regions without consideration of the compartmentalization of the neurotransmitter is only of limited value to use in an attempt to correlate elevation of GABA levels and pharmacological effects.
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PMID:Relationship between drug-induced increases of GABA levels in discrete brain areas and different pharmacological effects in rats. 642 17

TRH and PS-24 (a TRH peptidase resistant analogue) induce different effects on body temperature and motor activity in rats kept at 4 degrees C. PS-24 induced hypothermia, but TRH did not. PS-24 induced hypermotility, while TRH induced slight hypomotility. The thermal effect of TRH in hypophysectomized rats was similar to its effect in control intact rats, but PS-24 induced marked hypothermia in hypophysectomized rats. While TRH partially blocked d-amphetamine-induced hypothermia, PS-24 induced marked hypothermia in hypophysectomized rats. While TRH partially blocked d-amphetamine-induced hypothermia were blocked in olfactory tubercle-lesioned rats. The data indicate that the thermal effects of PS-24 are mediated by the dopaminergic neurons in the nucleus accumbens and are reversible by pretreatment with haloperidol in hypophysectomized rats. In addition, no correlation between the effects of the treatments on thermoregulation and motor activity was found.
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PMID:Effects of TRH and PS-24 on colonic temperature and motor activity of rats: possible role of dopamine. 679 10

Behavioral pharmacological properties of mianserin (1,2,3,4,10,14b-hexahydro-2-methyldibenzol[c,f]pyrazino [1.2-a]azepine monohydrochloride) were investigated in comparison with imipramine (IMP) and amitriptyline (ATP). Mianserin antagonized reserpine-induced hypothermia but to a much lesser extent than IMP or ATP, and did not block the ptosis evoked by reserpine or tetrabenazine. Amphetamine-induced stereotyped behavior was significantly enhanced by both IMP and ATP, but not by mianserin. Unlike IMP or ATP, haloperidol-induced catalepsy in the rat was not blocked by mianserin. Like IMP or ATP, mianserin did not suppress the convulsions induced by bemegride or strychnine in the mouse, and or emetic action of apomorphine in the dog, while only mianserin did not block the convulsions evoked by electric shocks. Mianserin more strongly potentiated the anesthetic action of thiopental than did IMP. ATP showed strong muscle relaxant action and the impairment of coordinated motor activities both in mice and rats, in the inclinated screen test and rotarod test, while, like IMP, these actions of mianserin were significant only in the rat. Catalepsy was not induced nor was the righting reflex suppressed by mianserin. In the low spinal cat, mianserin did not depress the amplitude of extensor MSR. Moreover, the MSR inhibition induced by conditioning stimulation of ipsilateral cutaneous afferents and the MSR potentiation evoked by conditioning stimulation of contralateral saphenous nerve were unaffected by mianserin. The curious behavior of mice and rats was significantly and dose-dependently suppressed by mianserin, and tended to be suppressed by ATP, while an enhancement was seen with IMP in large doses. Mianserin was the most potent in suppressing the fighting behavior induced by long-term isolation of the mouse, and was the weakest in suppressing electric-stimulation-induced fighting behavior, compared with IMP and ATP. Mianserin showed no significant suppression of the muricide behavior of the olfactory bulbectomized rat, while IMP significantly suppressed it. No significant differences were observed among mianserin, IMP and ATP as to their actions on the conflict behavior and the shuttle-box type conditioned avoidance behavior of the rat. These results indicate that behavioral pharmacological actions of mianserin were not always the same as those of IMP and ATP. Therefore, mianserin may be a new antidepressant with mechanisms of action which differ from that of the usual tricyclic antidepressants.
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PMID:[Behavioral pharmacology of mianserin hydrochloride, a new antidepressant (author's transl)]. 719 23

Pharmacological properties of 2-(4-methylamino-butoxy)-diphenylmethane hydrochloride (MCI-2016) were examined in comparison with those of other antidepressants. MCI-2016 significantly antagonized the hypothermia and depression-like syndrome produced by reserpine injection. Furthermore, the drug exhibited such activities as antitetrabenazine and anti-cataleptic actions, and potentiation of the behavioural excitation induced by yohimbine, methamphetamine and L-dopa. MCI-2016 showed a definite suppressive effect on muricidal activity in olfactory bulb removed rats and the long-term isolation-induced fighting in mice without causing apparent motor disturbance. Judging from the effects of the drug on in vitro response to noradrenaline (NA) and serotonin (5-HT), and on p-chloramphetamine-induced hypermotility, it is suggested that MCI-2016 is a selective potentiator of NA presumably due to an inhibition of NA uptake. Anticholinergic and sedative actions of MCI-2016 were considerably weaker than those of amitriptyline and imipramine. Acute toxicity of MCI-2016 was the weakest among the drugs tested. These pharmacological profiles may suggest a potential clinical utility of MCI-2016 as a new psychotropic agent having an antidepressant activity.
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PMID:Pharmacological evaluation of 2-(4-methylaminobutoxy)diphenylmethane hydrochloride (MCI-2016), a new psychotropic drug with antidepressant activity. 719 35

The preferential dopamine (DA) D3 versus D2 receptor agonist, (+)-7-OH-DPAT, dose-dependently decreased DA synthesis in the nucleus accumbens, olfactory tubercles, striatum and frontal cortex. This action was potently mimicked by several other high-potency D3 agonists: CGS 15855A, (-)-quinpirole, quinelorane and N-0434. In contrast, piribedil, which displays a mild preference for D2 sites, was less active. Across eight agonists, potency for inhibition of DA synthesis correlated more potently to affinity at D3 (r = .82 +/- .04) than D2 receptors (r = .60 +/- .06, P < .05). Correlations were also marked to potency for induction of a further D3-mediated response, hypothermia (r = .93 +/- .02). The novel and selective D3 versus D2 antagonist, (+/-)-S 11556, attenuated the action of (+)-7-OH-DPAT in each structure. This action was shared by its active (+)-eutomer, (+)-S 14297, whereas its inactive (-)-distomer, (-)-S 17777, was ineffective. (+)-S 14297 similarly attenuated the inhibitory action of CGS 15855A and (-)-quinpirole upon DA synthesis, whereas it failed to modify inhibition of striatal DA synthesis by the alpha 2-adrenergic receptor agonist, clonidine. As compared with the D2/D3 receptor antagonist, haloperidol, neither (+/-)-S 11566 nor (+)-S 14297 modified DA turnover upon administration alone. Furthermore, across (nine) antagonists, potency in facilitating DA synthesis more powerfully correlated to affinity at D2 (r = .94 +/- .01) than D3 (r = .73 +/- .01) sites (P < .01). Correlations were also marked to potency for induction of catalepsy (r = .91 +/- .01) and prolactin secretion (r = .89 +/- .01) but not for antagonism of (+)-7-OH-DPAT-induced hypothermia (r = .60 +/- .01). In freely moving rats, (+)-7-OH-DPAT dose-dependently reduced dialysate concentrations of DA in the nucleus accumbens and contralateral striatum: this action was potently mimicked by CGS 15855A, but only weakly so by piribedil. (+)-S 14297 markedly attenuated the action of (+)-7-OH-DPAT, whereas (-)-S 17777 was inactive. In contrast, haloperidol completely blocked the action of (+)-7-OH-DPAT. Finally, in distinction to haloperidol, upon administration alone, (+)-S 14297 did not significantly enhance the release of DA. In conclusion, these data suggest that D3 (auto)receptors control synthesis and release of DA in dopaminergic pathways innervating the limbic system, cortex and striatum.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Functional correlates of dopamine D3 receptor activation in the rat in vivo and their modulation by the selective antagonist, (+)-S 14297: II. Both D2 and "silent" D3 autoreceptors control synthesis and release in mesolimbic, mesocortical and nigrostriatal pathways. 747 81

This review reports anatomical studies evaluating central and peripheral alpha 2- and beta-adrenoceptors. The results suggest abnormalities exist in the noradrenergic system in depressed patients. Most animal models involve the use of stress to simulate depression in man. All models that have been developed lead to differential changes in noradrenergic function. We have assessed the effects of reboxetine, a novel, selective noradrenaline-reuptake inhibitor (NARI) in olfactory bulbectomised rats, a procedure that induces significant changes in amygdala function. Reboxetine is an effective antidepressant in the forced swim test and open field test in bulbectomised rats. Unlike the tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs), reboxetine is ineffective in the 8-OH-DPAT hypothermia test, indicating that reboxetine is selective for the noradrenergic system. Owing to the abnormalities that occur in depression, it would seem sensible to target the noradrenergic system for treatment of this condition.
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PMID:Noradrenaline in basic models of depression. 916 6

Amisulpride is a benzamide derivative with a unique neurochemical and psychopharmacological profile. This compound has selective affinity for human dopamine D3 and D2 receptor subtypes in vitro (binding constant, K approximately 3 nmol/l) and blocks functional responses mediated by these receptors. In ex vivo binding studies, amisulpride is twice as selective for D3 as for D2 receptors. At low doses, it preferentially blocks presynaptic dopamine autoreceptors (increase in dopamine release in vivo in the rat olfactory tubercle, 50% effective dose, ED50 3.7 mg/kg), while postsynaptic dopamine receptor antagonism is apparent at higher doses (decrease in striatal acetylcholine levels, ED50 approximately 60 mg/kg). Anisulpride preferentially stimulates dopamine synthesis and displaces 3H-raclopride binding in vivo in the limbic system rather than the striatum. It antagonizes apomorphine-induced hypothermia in mice and amphetamine-induced hypermotility in rats at low doses (ED50 2-3 mg/kg), blocks apomorphine-induced climbing and spontaneous grooming in mice, blocks apomorphine-induced gnawing in rats at higher doses (ED50 19-115 mg/kg) and does not induce catalepsy at 100 mg/kg. The preferential antagonism by amisulpride of presynaptic D2/D3 receptors is reflected behaviourally in the potent blockade of apomorphine-induced effects mediated by dopamine autoreceptors (yawning and hypomotility: ED50 0.2 and 0.3 mg/kg, respectively) compared with those medicated by postsynaptic D2 receptors (e.g. gnawing: ED50 115 mg/kg). Moreover, low doses of amisulpride induce prohedonic (potentiation of food-induced place preference) effects in rats. The atypical neurochemical and psychopharmacological profiles of amisulpride may explain its therapeutic efficacy on both positive and negative symptoms of schizophrenia.
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PMID:Amisulpride: from animal pharmacology to therapeutic action. 921 65

During the first 2 to 3 weeks of life, isolated neonatal mice emit ultrasonic vocalizations, with various conditions such as hypothermia or olfactory or tactile stimulation eliciting this behavior. Although it is known that pup vocalizations stimulate prompt expression of maternal behavior, the communicative role of infant ultrasonic calls is still a matter of investigation. A fine-grained spectrographic analysis of ultrasonic calls emitted by pups exposed to different conditions was performed. Forty 8-day-old outbred CD-1 mice (Mus musculus) were isolated from their mothers and littermates and randomly exposed to one of the following conditions: (a) odor from the nest, (b) social isolation, (c) low temperature-isolation, (d) tactile stimulation, or (e) odor from a conspecific adult male. Upon consideration of the spectrogram typology and emission frequency interval, it appears that the conditions under which vocalizations are emitted influence the sound characteristics of call production.
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PMID:Ultrasonic vocalizations by infant laboratory mice: a preliminary spectrographic characterization under different conditions. 981 Apr 75


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