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)

Trimipramine (TRI), which shows a clinical antidepressant activity, is chemically related to imipramine but does not inhibit the reuptake of noradrenaline and 5-hydroxytryptamine, nor does it induce beta-adrenergic down-regulation. The mechanism of its antidepressant activity is still unknown. The aim of the present study was to find out whether TRI given repeatedly was able to induce adaptive changes in the dopaminergic and alpha1-adrenergic systems, demonstrated by us previously for various antidepressants. TRI was given to male Wistar rats and male Albino Swiss mice perorally twice daily for 14 days. In the acute experiment TRI (given i.p.) does not antagonize the reserpine hypothermia in mice and does not potentiate the 5-hydroxytryptophan head twitches in rats. TRI given repeatedly to rats increases the locomotor hyperactivity induced by d-amphetamine, quinpirole and (+)-7-hydroxy-dipropyloaminotetralin (dopamine D2 and D3 effects). The stereotypies induced by d-amphetamine or apomorphine are not potentiated by TRI. It increases the behaviour stimulation evoked by phenylephrine (given intraventricularly) in rats, evaluated in the open field test as well as the aggressiveness evoked by clonidine in mice, both these effects being mediated by an alpha1-adrenergic receptor. It may be concluded that, like other tricyclic antidepressants studied previously, TRI given repeatedly increases the responsiveness of brain dopamine D2 and D3 (locomotor activity but not stereotypy) as well as alpha1-adrenergic receptors to their agonists. A question arises whether the reuptake inhibition is of any importance to the adaptive changes induced by repeated antidepressants, suggested to be responsible for the antidepressant activity.
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PMID:Repeated trimipramine induces dopamine D2/D3 and alpha1-adrenergic up-regulation. 966 Jan 11

Pharmacological effects of acute treatment with venlafaxine (VEN), a clinically active antidepressant [a noradrenaline (NA) and 5-hydroxytryptamine (5-HT) reuptake inhibitor without any affinity for neurotransmitter receptors] were studied in mice and rats. VEN inhibited the reserpine- or apomorphine-induced hypothermia and enhanced the L-5-HTP-induced head twitches in mice. It reduced the immobility time in Porsolt's test in mice and rats, but either did not change the locomotor activity (mice) or decreased it (rats). VEN reduced the locomotor hyperactivity induced by amphetamine (AMP), apomorphine (APO) and quinpirole (QUI), as well as the APO-induced stereotypy; the stereotypy induced by AMP in rats was prolonged. VEN neither changed the clonidine-induced aggressiveness in mice nor the behavioral syndrome induced by oxotremorine in rats. The obtained results indicate that VEN, given acutely, shows a pharmacological profile similar to that of tricyclic NA and 5-HT reuptake inhibitors. In contrast to the antidepressants mentioned above, VEN does not exhibit an alpha 1-adrenolytic or a cholinolytic activity (in vivo tests).
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PMID:Pharmacological profile of venlafaxine, a new antidepressant, given acutely. 979 62

A series of new indolylalkylamides 3-18 and alkylamines 19-26 has been prepared in the search of novel 5-hydroxytryptamine (5-HT) uptake inhibitors. Synthesis of N-2,3 or 4-pyridinyl-(indol-3-yl) acetamides and propionamides 3-10 was achieved starting from the corresponding Ph3P/BrCCl3 or DCC-activated acids. Reduction of the pyridine nucleus led to the N-piperidinylalkylamides 15-18 via the tetrahydropyridinyl derivatives 11-14, and LiAlH4 reduction afforded the desired amines 19-26. The affinity of these compounds for 5-HT and also dopamine (DA) and noradrenaline (NA) uptake sites was measured. Among the 16 studied amides only N-(methylpiperidin-3-yl)-(indol-3-yl) propionamide 16 exhibited a moderate 5-HT uptake inhibitory effect: 38% at 10 mu mol/l. In contrast the N-pyridinyl-(indol-3-yl)alkylamines 19-26 exerted high inhibition at this concentration and two of them, 23 and 24, remained very efficient at 0.1 mu mol/l. Optimal activity was observed in the 4-pyridinyl subseries and was compatible with variation (n = 1, 2) of the length of the interspacing alkylamino chain. Although 23 and 24 were about 17-fold less active than indalpine as 5-HT uptake inhibitors, they demonstrated, like indalpine, excellent selectivity for the 5-HT uptake site versus the DA uptake site. Both amines inhibited tetrabenazine-induced hypothermia and potentiated 5-HTP-induced behavioural effects in mice. The absence of 3,4-dioxyphenylalanine (dopa)-induced behavioural effects with compound 24 suggests possible antidepressant activity through selective inhibition of central neuronal serotonin uptake and/or increased monoamine release.
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PMID:Synthesis and pharmacological evaluation of new (indol-3-yl)alkylamides and alkylamines acting as potential serotonin uptake inhibitors. 1008 76

Venlafaxine (VEN) is a representative of a new class of antidepressants (SNRIs) which inhibit selectively the uptake of serotonin and noradrenaline, but--in contrast to tricyclics--show no affinity for neurotransmitter receptors. The present study was aimed at determining whether repeated VEN (given twice daily for 14 days) induced adaptive changes in the alpha 1-adrenergic, dopamine and serotonin systems, similar to those reported by us earlier for tricyclic antidepressants. The results indicate that VEN potentiates the clonidine-induced aggressiveness and the methoxamine-induced exploratory hyperactivity, both these effects being mediated by alpha 1-adrenoceptors. VEN increased the hyperlocomotion induced by D-amphetamine and (+/-)-7-OH-DPAT. Neither the apomorphine and quinpirole hyperlocomotion, nor the apomorphine and D-amphetamine stereotypies were changed. VEN did not affect the behavioural syndrome induced by 8-OH-DPAT (a 5-HT1A effect), and decreased both the head twitch reaction induced by L-5-HTP or (+/-)DOI and the hyperthermia induced by trifluoromethylphenylpiperazine, all those effects being mediated by 5-HT2 receptors. Repeated VEN did not change the hypothermia evoked by oxotremorine (a central cholinergic agonist). The above results indicate that repeated VEN increases--as do tricyclics--the responsiveness of alpha 1-adrenergic and dopaminergic (mainly D3) systems and decreases the responsiveness of the 5-HT2 system. It may be concluded that the lack of affinity for neurotransmitter receptors is of no importance to the development of adaptive changes in the studied systems, observed after repeated treatment.
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PMID:Pharmacological effects of venlafaxine, a new antidepressant, given repeatedly, on the alpha 1-adrenergic, dopamine and serotonin systems. 1022 39

Pharmacological effects of acute treatment with milnacipran (MIL), a clinically active antidepressant (a noradrenaline [NA] and 5-hydroxytryptamine [5-HT] reuptake inhibitor without any affinity for neurotransmitter receptors) were studied in mice and rats. MIL inhibited the reserpine- or apomorphine-induced hypothermia in mice and enhanced the L-5-hydroxytryptophan-induced head twitches in rats. It reduced the immobility time in Porsolt's test in mice and rats, but either did not change the locomotor activity (mice) or decreased it (rats). MIL changed neither the clonidine-induced aggressiveness in mice nor the behavioral syndrome induced by oxotremorine in rats. The obtained results indicate that MIL, given acutely, shows a pharmacological profile similar to that of tricyclic NA and 5-HT reuptake inhibitors. In contrast to the antidepressants mentioned above, MIL does not exhibit an alpha1-adrenolytic or cholinolytic activity (in vivo tests).
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PMID:Pharmacological profile of milnacipran, a new antidepressant, given acutely. 1054 Sep 63

The pharmacological properties of the 5-hydroxytryptamine (HT)(1A) receptor agonist (R)-3,4-dihydro-N-isopropyl-3-(N-isopropyl-N-propylamino)-2H-1-benzopyran-5-carboxamide (NAE-086) were examined with in vitro and in vivo techniques. Receptor binding studies demonstrated that NAE-086 was a high-affinity and selective 5-HT(1A) receptor ligand with a K(i) value of 4.5 nM in membranes from rat hippocampus. Of 32 other receptors examined NAE-086 had a modest affinity only for the 5-HT(7) receptor (K(i) = 240 nM). NAE-086 inhibited VIP-stimulated adenylyl cyclase activity in GH(4)ZD10 cells with 79% of the efficacy of 5-HT. This inhibition was blocked by the 5-HT(1A) receptor (and beta-adrenoceptor) antagonist (-)alprenolol. A minor metabolite of NAE-086 in rats, (R)-3,4-dihydro-3-(N-isopropyl-N-propylamino)-2H-1-benzopyran-5-carboxamide had a similar receptor profile but had 17 times higher affinity for the 5-HT(1A) receptor (K(i) = 0.26 nM). In vivo, NAE-086 induced all the typical effects of a 5-HT(1A) receptor agonist in rats: it decreased 5-HT synthesis (5-HTP accumulation) and 5-HT turnover (measured as the ratio of 5-hydroxyindoleacetic acid/5-HT), increased corticosterone secretion, induced the 5-HT(1A) syndrome (flat body posture and forepaw treading), inhibited the cage-leaving response, and caused hypothermia. All the responses mediated by postsynaptic 5-HT(1A) receptors were attenuated after single or repeated treatment of the rats with NAE-086. Simultaneously with the development of the tolerance to 5-HT(1A) receptor-mediated responses, 5-HT(2A) receptor-mediated responses were enhanced, as judged from the increased number of spontaneous and/or agonist [1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane]-induced wet-dog shake responses. The significance of this behavioral effect in relation to clinical observations is discussed.
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PMID:The pharmacological profile of (R)-3,4-dihydro-N-isopropyl-3-(N-isopropyl-N-propylamino)-2H-1-benzopyran-5-carboxamide, a selective 5-hydroxytryptamine(1A) receptor agonist. 1171 72

Aromatic L-amino acid decarboxylase (AADC - E.C. 4.1.1.28) converts L-dopa to dopamine and 5-hydroxytryptophan to serotonin. Inherited deficiency of this enzyme leads to decreased brain levels of these neurotransmitters. Clinically this results in the development of a progressive neurometabolic disorder characterized by severe hypotonia, dystonic and choreoathetoid movements, oculogyric crises, and hypothermia from infancy. Here we describe the clinical, biochemical and molecular details of two affected brothers, one of whom, despite the lack of AADC, presented with hyperdopaminuria. In addition, we detail his reactions to treatment with dopaminergic agonists, monoamine oxidase inhibitors and pyridoxine.
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PMID:Aromatic L-amino acid decarboxylase deficiency with hyperdopaminuria. Clinical and laboratory findings in response to different therapies. 1236 91

The infusions of the aerial parts in blossom of Hypericum canariense, H. glandulosum, H. reflexum and H. grandifolium (Hypericaceae) were evaluated for their pharmacological activity on the central nervous system in mice using various behavioural models including locomotor and muscle relaxant activity, effect on normal body temperature, pentobarbital-induced sleep, oxotremorine and tetrabenazine-induced syndrome, apomorphine-induced hypothermia and 5-hydroxytryptophan-induced head twitches, as well as a forced swimming test. These infusions did not alter significantly the locomotor activity, pentobarbital induced sleeping time and body temperature, with the exception of H. canariense which produced a slight but significant hypothermia. Additionally, no muscle relaxant or anticholinergic activity were observed. These infusions antagonized the ptosis and/or motor depression induced by tetrabenazine as well as shortening the immobility time in the forced swimming test. The observations suggest that the infusions of these Hypericum species possess antidepressant activity in mice, without inducing muscle relaxation, anticholinergic and sedative properties.
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PMID:Evaluation of the central properties of several Hypericum species from the Canary Islands. 1245 77

Neuropharmacological studies were conducted in mice with a number of hetero[2,1]benzothiazepine derivatives, analogues of tianeptine. Seven of the 12 compounds under study potentiated the actions of 5-hydroxytryptophan (5-HTP, 50 mg/kg i.p.) and/or antagonised the hypothermia induced by high doses of apomorphine. Moreover, some of them inhibited the head twitches induced by 5-HTP (250 mg/kg i.p.) and the stereotyped behaviour and/or climbing behaviour of low doses of apomorphine. These compounds also produced a slight inhibition of exploratory behaviour in the holeboard test. On the other hand, no significant muscle relaxant, anticonvulsant and anxiolytic activities were observed at any dose employed. Together, these data suggest that some of the compounds under study exert antidepressant and neuroleptic effects in mice with no muscle relaxant, anxiolytic and anticonvulsant activities.
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PMID:Neuropharmacological study of hetero[2,1]benzothiazepine derivatives analogues of tianeptine. 1259 31

The psychopharmacological effects of a number of thieno and pyrazolo[2,1] benzothiazepine derivatives as well as several synthetic intermediate compounds were investigated in mice. Previously published studies in mice have shown that some of these compounds were effective in the tetrabenazine and Porsolt tests. In the present study, 7 of the 15 compounds under study clearly antagonized the apomorphine (16 mg/kg s.c.)-induced hypothermia, but no significant potentiation of the 5-hydroxytryptophan (5-HTP) and amphetamine actions was found. Five of them inhibited the syndrome induced by 5-HTP (250 mg/kg i.p.). Moreover, some of them were effective in the plus-maze test and antagonized the apomorphine (3 mg/kg s.c.)-induced effects. On the other hand, these compounds produced a moderate inhibition of exploratory behaviour in the hole-board test, but they had no significant muscle relaxant and anticonvulsant activities. The results indicate that some of the compounds under study combine a spectrum of antidepressant, anxiolytic and neuroleptic properties in mice with a lack of muscle relaxant and anticonvulsant activities.
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PMID:Psychopharmacological effects of tianeptine analogous hetero[2,1] benzothiazepine derivatives. 1260 9


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