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)

Tiflucarbine (TVX P 4495), a new putative antidepressant drug (AD) with a chemical novel among AD's [9-ethyl-4-fluoro-1-methyl-7,8,9,10-tetrahydrothieno (3,2-e)-pyrido(4,3-b)indole lactate], a potent inhibitor of the 5-hydroxytryptamine (5-HT) uptake, was studied in rats and mice, mostly with regard to its possible effect on the noradrenaline (NA) uptake and 5-HT postsynaptic receptors. Tiflucarbine exerted no effect on the reserpine hypothermia, attenuated the apomorphine hypothermia and enhanced the TRH-induced hyperthermia. It did not prevent tryptamine convulsions or the fenfluramine-induced hyperthermia, and inhibited the L-5-hydroxytryptophan-induced head twitches (at a high dose only). It stimulated the hind limb flexor reflex preparation of the spinal rat in cyproheptadine-reversible manner. In the behavioral despair test it shortened the immobility time. Tiflucarbine administered repeatedly enhanced the D-amphetamine-induced locomotor hyperactivity and inhibited the clonidine-induced aggressiveness. The results indicate that tiflucarbine exhibits characteristics of a poor inhibitor of the NA uptake (irrespective of its strong inhibitory effect on the 5-HT uptake), and has no effect on 5-HT2 postsynaptic receptors. When used repeatedly, it enhances--like other AD--responsiveness of the central dopamine system.
Pol J Pharmacol Pharm
PMID:Some central effects of tiflucarbine, a new potential antidepressant drug. 282 40

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.
Pol J Pharmacol Pharm
PMID:The role of alpha 2-adrenoceptors in the mechanism of action of antidepressant drugs. 284 26

Prostacyclin (PGI2) administered icv into the lateral rat brain ventricle in a dose of 1 and 10 micrograms caused hypothermia and catalepsy. Joint administration of PGI2 and chlorpromazine produced a greater cataleptic effect than that observed after the neuroleptic alone. Cimetidine (CMT) 2 g/kg po administered 60 min before PGI2 icv injection inhibited hypothermic and cataleptogenic action of PGI2. CMT blocked the cataleptogenic effect of chlorpromazine as well as combination of it with PGI2. CMT inhibited cataleptogenic effect of haloperidol, but it did not block the catalepsy induced by joint administration of haloperidol and PGI2. PGI2 did not change concentration of noradrenaline and dopamine in different brain areas. The results indicate that H2 receptors take part in some central pharmacological effects of PGI2 in rats.
Pol J Pharmacol Pharm
PMID:Influence of H2 receptors blockade upon some central effects of prostacyclin in rats. 287 Apr 86

Alprazolam, a new benzodiazepine from triazolobenzodiazepine group, produced anxiolytic action in the conflict test with potency similar to that of diazepam. The myorelaxant activity of the drug was relatively weak. Unlike desipramine, alprazolam failed to reduce the immobility of rats in the forced swim test and was unable to prevent clonidine-induced hypothermia. Alprazolam, unlike desipramine, failed also to potentiate behavioral effect of noradrenaline injected into the hippocampus. Alprazolam after acute but not chronic administration antagonized the synchronizing effect of clonidine on EEG pattern. On the other hand, alprazolam similarly to tricyclic antidepressants, prevented the suppression of dominance behavior by clonidine in rats competing for food. The results indicate that alprazolam acts only weakly upon noradrenergic mechanisms related to depression and to antidepressant action of drugs.
Pol J Pharmacol Pharm
PMID:Comparative studies on antidepressant action of alprazolam in different animal models. 288 37

The central adrenergic blocking activity of adimolol (ADL) was studied in rats and mice in the tests which can differentiate beta-, alpha 1-, and alpha 2-adrenolytic effects. Clenbuterol- and salbutamol-induced sedation in rats (open field test) and clenbuterol-induced hyperthermia (at high ambient temperature) were antagonized by low doses of ADL (0.1-1.0 mg/kg ip). ADL (10 mg/kg ip) attenuated the clonidine-induced aggression in mice, and its higher doses (20 and 40 mg/kg ip) depressed the hind limb flexor reflex of the spinal rat and counteracted the stimulatory action of clonidine. ADL at doses from 2.5 to 40 mg/kg ip affected neither the clonidine-induced sedation in rats and mice (locomotor activity, open field test), nor the hyperthermia (at high temperature). The hypothermia (at a room temperature of 21 degrees C) induced by clonidine was partially antagonized. The Ki values for ADL displacement of 3H-dihydroalprenolol and 3H-prazosin binding in the rat cerebral cortex were 1.2 nM and 951 nM respectively. These results indicate that ADL is a potent antagonist of central beta-adrenoceptors and has a weaker alpha 1-adrenolytic action. The central alpha 2-antagonistic effect is either very weak or absent.
Pol J Pharmacol Pharm
PMID:Central beta- and alpha-adrenolytic activities of adimolol. 289 Jan 41

Different ergot structures (lumilysergol and lysergol) were chlorinated or brominated in the position 2, and the development of antidopaminergic activity was studied. The tested 2-halo-lysergols exerted neuroleptic-like action indicated by the suppression of conditioned avoidance response (CAR), and other effects characteristic of dopamine antagonists (cataleptogenic effect, prevention of amphetamine-induced toxicity, inhibition of L-DOPA-induced hyperactivity, lowering of spontaneous body temperature, antagonism of apomorphine-induced hypothermia). A second halogen substitution in the position 8 of the lysergol structure left the CAR suppression activity untouched, but abolished other dopamine antagonistic effects. This unique psychopharmacological profile refers to potential usefulness of the compounds in schizophrenia, and at the same time perhaps in particular forms of Parkinson's disease or tardive dyskinesia.
Pol J Pharmacol Pharm
PMID:Substituted ergolines: potential antipsychotics with unique profile. I. Psychopharmacological characterization. 290 63

In contrast to imipramine, chlorprothixene (CPX) and levomepromazine (LMZ) given chronically did not affect clonidine-induced hypothermia and depression of noradrenaline synthesis rate, while similarly to imipramine and citalopram depressed the density of cortical 3H-clonidine binding sites and increased their affinity. Two week treatment with the antidepressants did not affect the parameters of 3H-dihydroalprenolol binding sites, while spiroperidol administration increased their density, without changing KD values. The data suggest that changes in alpha 2 adrenoceptor population parameters may be a general characteristics of antidepressant treatment, but not necessarily followed by changes in clonidine effects.
Pol J Pharmacol Pharm
PMID:Action of antidepressant neuroleptics, chlorprothixene and levomepromazine, on the central noradrenergic system: comparison with other antidepressants. 300 33

Three weeks of treatment with desipramine (DMI) and amitriptyline (AMI) reduced the hypothermic action of clonidine in rats. Both electrolytic and 6-hydroxydopamine lesions of the locus coeruleus (LC) and administration of DSP-4 counteracted the reduction of clonidine hypothermia produced by antidepressants. Lesions of the LC and DSP-4 administration also antagonized the anti-immobility action of single doses of DMI but failed to modulate the action of AMI in the forced swim test. Chronic DMI action on the rat immobility was reduced by 6-hydroxydopamine lesions of the LC: other lesions (electrolytic, DSP-4) were ineffective. Electrical stimulation of the LC increased the rat activity in the forced swim paradigm, producing an effect similar to that of antidepressants. The anti-immobility effect of DMI as well as LC stimulation were antagonized by drugs blocking alpha-adrenoceptors (phenoxybenzamine, prazosin) but not by propranolol, a non-selective antagonist of beta-adrenoceptors. On the other hand, the anti-immobility action of AMI was unchanged by all adrenolytics used in that study. The results indicate that the LC system and alpha 1-adrenoceptors play an important role in the antidepressive action of DMI, but not AMI, in the forced swim test.
Pol J Pharmacol Pharm
PMID:On the role of noradrenergic neurotransmission in the action of desipramine and amitriptyline in animal models of depression. 302 58

3,5-Dinitrobenzoic acid hydrazide (1) treated with substituted phenyl isothiocyanates (2a-2d) in dry benzene yields N'-aryl-N4-(3,5-dinitrophenyl) thiosemicarbazides (3-6), which cyclizes in NaOH solution yielding 1-aryl-5-(3,5-dinitrophenyl)-2-mercapto-1,3,4-triazoles (7-10). The reaction of the appropriate 7-10 respectively with chloroacetic acid and 4-chlorobenzoic acid in NaOH solution gave 1-aryl-5-(3.5-dinitrophenyl)-2-mercapto methyl/phenyl carboxy-1,3,4-triazoles (11-18). All the compounds were found to be relatively non toxic (ALD greater than 1000 mg/kg), whereas in their gross CNS observations the compounds were found to be psychotropic. They increased or decreased spontaneous locomotor activity and at high doses produced writhing and mild hypothermia. Some of them mildly affected the cardiovascular system and showed antiinflammatory activity.
Pol J Pharmacol Pharm
PMID:Synthesis and pharmacological screening of some new triazoles. 324 71

1-Pyridyl-3,4-dihydro-beta-carbolines (2a-2f) were synthesized by two methods. The central action of these compounds was investigated in mice and rats using behavioral tests. The most active 6-methoxy-1-(3-pyridyl)-3,4-dihydro-beta-carboline (2e) possesses potential antidepressant properties, as it reversed the effects of reserpine (sedation, hypothermia and ptosis), potentiated the stimulation induced by levodopa given jointly with pargyline, and reduced the immobility time in the despair test. Moreover, compound 2e inhibited the spontaneous locomotor activity, evoked tremor and produced an analgesic effect.
Pol J Pharmacol Pharm
PMID:1-Pyridyl-3,4-dihydro-beta-carbolines: synthesis and central action. 349 88


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