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 effect of repeated treatment (5 and 10 mg/kg, po, twice daily, 14 days) with sertraline and citalopram (antidepressants which selectively inhibit the reuptake of 5-hydroxytryptamine (5-HT)) on the responsiveness of different 5-HT receptors to their agonists, was examined in rats and mice. Sertraline and citalopram (both at a dose 5 and 10 mg/kg) antagonized (the first one more potently) the hypothermia induced in mice by 8-OH-DPAT (a 5-HT1A agonist), but not the behavioural syndrome induced in rats by this substance. The m-chlorophenylpiperazine-induced hypothermia in mice (a 5-HT1B effect) was increased by sertraline and citalopram (only in a dose of 10 mg/kg). Both antidepressants, given repeatedly (as well acutely) attenuated exploratory hypoactivity induced in rats by m-chlorophenylpiperazine (a 5-HT1C effect). L-5-HTP-induced head twitches in mice (5-HT2 effect) were antagonized dose-dependently by both repeated sertraline and citalopram. Both antidepressants (citalopram only in higher dose) reduced the fenfluramine-induced hyperthermia in rats (5-HT2 effect). The results indicate that sertraline and citalopram given repeatedly decrease the responsiveness of 5-HT1A (presynaptic) and 5-HT2 receptors but increase the responsiveness of 5-HT1B receptors to respective agonists.
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PMID:Effects of sertraline and citalopram given repeatedly on the responsiveness of 5-HT receptor subpopulations. 138 65

L-Methionine-D,L-sulfoximine (MSO) intraperitoneally or intracerebroventricularly (third ventricle) injected at convulsant doses induced a hypothermia, primarily associated with a syndrome of ataxia, in the restrained rat maintained at an ambient temperature of 23 degrees C. Depletion of brain serotonin (5-HT) by pretreatment with p-chlorophenylalanine (PCPA), p-chloroamphetamine (PCA), and d-fenfluramine (FFA) did not significantly modify the time course and magnitude of MSO-induced developing hypothermia but it enhanced abnormal motor behavior. Enhancement of 5-HT synthesis in MSO-submitted rats pretreated with 5-hydroxytryptophan (5-HTP) (200 mg/kg, IP) alone or 5-HTP (100 mg/kg, IP) preassociated with carbidopa (10 mg/kg, IP) suppressed significantly hypothermia, but it did not greatly modify motor disturbances. In conclusion, the neurocytochemical processes initiating hypothermia following administration of MSO to the rat appear to be linked to a slowdown of the rate of brain 5-HT turnover, maybe at the level of the midbrain raphe nuclei.
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PMID:Possible link between brain serotonin metabolism and methionine sulfoximine-induced hypothermia and associated behavior in the rat. 140 1

Some central effects of Ro 19-6327--a new MAO-B inhibitor--were studied in mice and rats. Given in low doses (1 or 3 mg/kg) Ro 19-6327 did not affect the locomotor activity of mice but its high dose (10 mg/kg) increased the activity. In rats Ro 19-6327 inhibited the locomotor activity but the effect was not dose dependent and not always significant. Ro 19-6327 did not change the locomotor activity in mice induced by L-DOPA (plus benserazide--an inhibitor of peripheral decarboxylase). The drug suppressed the reserpine-induced hypothermia and ptosis in mice and partly counteracted the apomorphine-induced hypothermia. It markedly enhanced (10 mg/kg) the amphetamine-induced stereotypy in rats. L-5-Hydroxytryptophan (L-5-HTP)-induced head twitch response was unchanged by Ro 19-6327. The drug given three times was inactive in forced swimming test. Repeated treatment with Ro 19-6327 (twice daily for 14 days) produced the enhancement of (+)-amphetamine- and nomifensine-induced hyperactivity in rats. Unlike a number of antidepressants, Ro 19-6327 did not potentiate the clonidine aggressiveness in mice, but--in contrast--inhibited it. The results suggest that Ro 19-6327 given repeatedly produces no changes in the responsiveness of the alpha-adrenergic system (in references to effects mediated by alpha 1-adrenoceptors). Adaptive changes in dopamine system are doubtful.
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PMID:Central effects of Ro 19-6327 given acutely and repeatedly. 166 12

The effects of repeated treatment of rats with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 1.0 mg/kg, subcutaneously, twice daily for 7 days, on the stimulation of post- and presynaptic 5-HT1A receptors were examined. The postsynaptic responses, hypothermia and inhibition of the cage-leaving response, evoked by 0.05 mg/kg 8-OH-DPAT, were measured 48 hr after the final injection. Another postsynaptic response, the 5-HT syndrome (flat body posture and forepaw treading) was observed after the third injection of 8-OH-DPAT (1.0 mg/kg s.c.). One presynaptic response examined was the 8-OH-DPAT-induced decrease in the concentration of 5-hydroxyindoleacetic acid (5-HIAA), that indicates a decrease in turnover of 5-HT, due to stimulation of 5-HT receptors on the cell bodies and measured as the ratio of 5-HIAA to 5-HT in the hippocampus, hypothalamus and medulla oblongata. Another presynaptic response was the 8-OH-DPAT-induced decrease in the accumulation of 5-hydroxytryptophan (5-HTP) in the hippocampus and hypothalamus, after inhibition of L-aromatic amino acid decarboxylase by 3-hydroxybenzylhydrazine (NSD 1015), that is due to stimulation of autoreceptors on the 5-HT cell bodies. The kinetic properties of 5-HT1A receptors in the cerebral cortex and hippocampus, hippocampus alone, hypothalamus and medulla oblongata were determined with [3H]8-OH-DPAT. It was found that the postsynaptic effects were markedly attenuated after the treatment, the hypothermic effect already after a single dose.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Different effects on the responses of functional pre- and postsynaptic 5-HT1A receptors by repeated treatment of rats with the 5-HT1A receptor agonist 8-OH-DPAT. 169 32

1. Parallel series of experiments were carried out in the rat and mouse in order to investigate the mechanism(s) underlying the hypothermia induced in rodents by the selective 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). 2. In the mouse, lesioning of central 5-hydroxytryptaminergic neurones (by use of the neurotoxin, 5,7-dihydroxytryptamine; 5,7-DHT) abolished the hypothermic response to 8-OH-DPAT, and depletion of brain 5-hydroxytryptamine (5-HT) levels (with the 5-HT synthesis inhibitor, p-chlorophenylalanine) markedly attenuated the response in this species. These pretreatments did not significantly attenuate 8-OH-DPAT-induced hypothermia in the rat, except for a significant attenuation of the response in 5,7-DHT-lesioned rats at the top dose of 8-OH-DPAT (1.0 mg kg-1, s.c.). 3. Pharmacological pretreatments which facilitate 5-HT release (selective 5-HT uptake inhibitors, precursor (5-hydroxytryptophan) loading, or fenfluramine), markedly attenuated or abolished 8-OH-DPAT-induced hypothermia in the mouse. These pretreatments generally had no significant effect on 8-OH-DPAT-induced hypothermia in the rat. 4. The selective noradrenaline uptake inhibitor, desipramine, had no effect on the hypothermic response to 8-OH-DPAT in either species. The selective dopamine uptake inhibitor, nomifensin, significantly increased the hypothermic response to 8-OH-DPAT in the mouse, but did not affect the response in the rat except at high, motor stimulant doses, when the response was attenuated. 5. These data are consistent with the hypothesis that 8-OH-DPAT-induced hypothermia is mediated by presynaptic autoreceptors in the mouse and by postsynaptic 5-HT1A receptors in the rat. Preliminary data also indicate an involvement of dopamine release in the mouse but not in the rat.
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PMID:Direct evidence for an important species difference in the mechanism of 8-OH-DPAT-induced hypothermia. 183 17

Our earlier studies showed that dihydropyridine calcium channel antagonists have some central pharmacological effects. Flunarizine is considered to be a calcium channel antagonist; therefore this study was aimed at investigating the effect of flunarizine (given in single doses of 5, 10 and 20 mg/kg p.o.) in behavioural models in which calcium channel antagonists of the dihydropyridine type were previously studied. Flunarizine inhibited the apomorphine-induced stereotypy and yawning behaviour in rats. It decreased the hypothermia induced by a low dose of apomorphine in mice, but not that one induced by high dose of it. The quinpirole-induced hypothermia was also reduced. In the tests used for evaluation of the effect on the serotonergic system, flunarizine decreased the 5-HTP-induced head twitches and partly antagonized the fenfluramine- and quipazine-induced hyperthermias (at a high ambient temperature). In the forced swimming test flunarizine was inactive in mice and rats. The obtained results indicate that flunarizine exerts central antagonistic effects on the dopaminergic and serotonergic systems and has no antidepressant activity. Flunarizine differs from calcium channel antagonists of the dihydropyridine type, which have no dopamine-antagonistic activity and show anti-depressant-like properties.
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PMID:Some central pharmacological effects of the calcium channel antagonist flunarizine. 203 9

Behavioral effects of setiptiline, a new tetracyclic compound (1,2,3,4-tetrahydro-2-methyl-9H-dibenzo [3,4:6,7] cyclohepta [1,2-C] pyridine maleate), were investigated to determine its pharmacological characteristics as an antidepressant in rats and mice, as compared with amitriptyline, a tricyclic antidepressant, and promethazine, a neuroleptic possessing an antihistaminic profile. Setiptiline exerted a weak stimulatory action on ambulation, spontaneous motor-activity, observed by the open field method in rats and potentiated the stimulatory effects of methamphetamine. Setiptiline also shortened the duration of immobility in rats forced to swim and inhibited catalepsy induced by haloperidol, yawning by physostigmine, body shaking as well as head twitch by 5-hydroxytryptophan in combination with Ro4-4602 and body shaking by morphine-withdrawal in rats. On the other hand, the drug did not exhibit an antagonistic effect on the hypothermia produced by reserpine in mice. From the results, it is suggested that setiptiline seems to have antidepressive activities that are pharmacologically dissimilar to those of tricyclic antidepressants.
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PMID:[Behavioral effects of a new antidepressant, setiptiline]. 204 13

The effects of carbamazepine (CBZ) on brain 5-hydroxytryptamine (5-HT) function were investigated in rodents pretreated with CBZ acutely or for 14 days. In behavioural experiments, mice pretreated with 14 days CBZ showed increased 5-HT2-mediated head twitch behaviour after injection of carbidopa (25 mg/kg) followed by 5-hydroxytryptophan (5-HTP, 100 mg/kg). However, no change in head twitches after 5-methoxy,N,N,-dimethyltryptamine (5MeODMT 5.0 mg/kg), a direct agonist, was observed. Chronic CBZ administration to rats did not alter either the behavioural syndrome induced by 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT, 1.0 mg/kg), an index of postsynaptic 5-HT1A responses, or hypothermia after 8-OH-DPAT (0.5 mg/kg) which is thought to reflect presynaptic 5-HT1A activity. Both hyperactivity and the behavioural syndrome seen after tranylcypromine (20 mg/kg) followed by L-tryptophan (100 mg/kg) were decreased by prior treatment with CBZ (14 days). Accumulation of 5-HTP after administration of the amino acid decarboxylase inhibitor NSD1015 (100 mg/kg) was decreased after acute CBZ (50 mg/kg) in hippocampus. However, after 14 days oral treatment no change in this measure of 5-HT synthesis was seen, in either hippocampus or frontal cortex. CBZ (50 microM) added to superfused brain slices did not affect potassium-stimulated [3H]-5-HT release. However, hippocampal slices from rats pretreated with CBZ (14 days) showed increased potassium-stimulated [3H]-5-HT release. CBZ (14 days) did not alter 5-HT2 binding in rat frontal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of carbamazepine on 5-hydroxytryptamine function in rodents. 213 52

We used an in vitro radioligand receptor binding assay with rat cerebral cortex, hippocampus and striatum membrane preparations to show that 1-[3-(3,4-methylenedioxyphenoxy)propyl]-4-phenyl piperazine (BP-554) had much higher affinity for 5-HT1A recognition sites than for 5-HT1-non-A, 5-HT2, benzodiazepine, dopamine D-2 and alpha 2-adrenergic recognition sites. The compound inhibited the activity of forskolin-stimulated adenylate cyclase in rat hippocampal membranes. Intraperitoneal injection of BP-554 to mice decreased the concentration of only 5-hydroxy-indoleacetic acid of the amines and their metabolites in the brain and decreased the accumulation of 5-hydroxytryptophan in the brain after decarboxylase inhibition by 3-hydroxybenzylhydrazine. Furthermore, the administration of BP-554 caused hypothermia and increased serum corticosterone levels in mice. The observed effects of BP-554 were similar to those of 8-hydroxy-2-(di-n-propylamino)tetralin. These results suggest that BP-554 acts as a selective 5-HT1A receptor agonist in vivo.
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PMID:Agonist activity of a novel compound, 1-[3-(3,4-methylenedioxyphenoxy)propyl]-4-phenyl piperazine (BP-554), at central 5-HT1A receptors. 253 78

The study examined the effect of both oxaprotiline (OXA) enantiomers on the serotonin system in rats and mice. (+)-OXA and (-)-OXA partly inhibit the behavioral syndrome induced by 8-OH-DPAT and 5-methoxy-dimethyltryptamine (5-MeODMT) in normal and reserpinized rats. Imipramine and desipramine produced a similar but less potent effect. (+)-OXA and, to a lesser extent, (-)-OXA antagonized the m-chlorophenylpiperazine (m-CPP)-induced hypothermia in mice. Imipramine and desipramine produced no such effect. (+)-OXA attenuated the head-twitch response to L-5-HTP in mice, but (-)-OXA has no such action. Neither enantiomer inhibited the fenfluramine-induced hyperthermia in rats nor antagonized m-CPP-induced stimulation of hind limb flexor reflex of spinal rat. The obtained results indicate that both enantiomers may have a 5-HT1B-antagonistic action and a less potent 5-HT1A-antagonistic one; on the other hand, they shown no 5-HT2-antagonistic activity.
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PMID:Pharmacological effects of oxaprotiline enantiomers on the central serotonin system. 253 22


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