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)

1. Different 5-hydroxytryptamine (5-HT) receptor subtypes mediate different behavioural responses. Compounds acting at more than one 5-HT receptor exert behavioural effects which may be the result of response competition or a specific interaction between pathways within the CNS. Therefore the mutual interaction between different 5-HT receptor subtypes was studied. 2. Hypothermia and hypoactivity in mice induced by the 5-HT1A-agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) could be attenuated by the preferential 5-HT1C-agonists MK 212, 1-(meta-chlorophenyl)-piperazine (mCPP) and m-trifluoromethyl phenyl piperazine (TFMPP), and by the mixed 5-HT2/1C-agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). The mixed 5-HT1A/1B-agonist CGS 12066B at 10 mg kg-1 potentiated hypothermia and had no effect on hypoactivity. 3. Forepaw treading in rats induced by the 5-HT1A-agonist 8-OH-DPAT was attenuated by the 5-HT1C-agonists MK 212 and mCPP. The 5-HT1C-agonist TFMPP had a bimodal effect: at low doses (less than 1 mg kg-1) it potentiated, and at higher doses (greater than 2.2 mg kg-1) it attenuated forepaw treading, the mixed 5-HT2/1C-agonist DOI produced 5-HT2-related behaviours and potentiated 8-OH-DPAT-induced forepaw treading. This indicates an attenuating effect of 5-HT1C-receptor activation and a potentiating effect of 5-HT2-receptor activation. CGS 12066B had no effect in this respect. 4. Head shakes in rats induced by DOI could be attenuated by 8-OH-DPAT, TFMPP, mCPP and MK 212. The ID50S were 0.03, 0.7, 0.1 and .2 mg kg-1, respectively. This suggests that a 5-HT2-receptor-mediated effect may be attenuated by activation of 5-HT1A- or 5-HT1c-receptors. CGS 12066B attenuated the head shake response but only at 10mg kg- '. 5. The results suggest that interactions exist between the different 5-HT receptor subtype-mediated events. Therefore, care is needed in drawing conclusions from functional measurements when compounds have more or less equal affinities for more than one 5-HT-receptor subtype.
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PMID:Behavioural evidence for functional interactions between 5-HT-receptor subtypes in rats and mice. 215 Jan 80

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 central action of 1-(2-pyrimidinyl)-piperazine (1-PP), a metabolite of ipsapirone, was studied in mice and rats. 1-PP decreased the locomotor activity and slightly increased the body temperature at an ambient temperature of 21 degrees C, not changing it at an ambient temperature of 28 degrees C. The examined substance antagonized clonidine effects (hypothermia, locomotor hypoactivity, stimulation of the hind limb flexor reflex of the spinal rat). Stimulation of the flexor reflex by St 587, an alpha 1-adrenoceptor agonist was not blocked by 1-PP. 1-PP-induced stimulation of the flexor reflex was blocked by cyproheptadine, ketanserin and pirenperone, but not by prazosin or yohimbine. Given in high doses, 1-PP evoked a flat body posture syndrome, but not forepaw treading or head twitches. The obtained results indicate that 1-PP has mainly an alpha 2-adrenolytic action and differs from ipsapirone in its profile.
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PMID:The central action of 1-(2-pyrimidinyl)-piperazine, an ipsapirone metabolite. 258 37

We investigated in mice the effects of one of the principal metabolites of buspirone and gepirone, 1-(2-pyridinyl)-piperazine (1-PmP), on hypothermia and reduced locomotion induced by clonidine (0.25 and 0.06 mg/kg, respectively), tests related to brain alpha-adrenergic function. Both effects were antagonized dose dependently by 1-PmP (1-16 mg/kg i.p.). Moreover, pretreatment with proadifen (50 mg/kg) prevented the reversal by buspirone and gepirone of clonidine-induced hypothermia. This suggests that 1-PmP could be responsible for some of the apparent noradrenergic effects of buspirone and gepirone.
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PMID:Pharmacological evidence for the involvement of 1-(2-pyridinyl)-piperazine (1-PmP) in the interaction of buspirone or gepirone with noradrenergic systems. 288 93

The putative serotonin (5-HT)1A agonist 1-[2-(4-aminophenyl)ethyl]-4-(3-trifluormethylphenyl) piperazine (LY165163, PAPP) induces hyperphagia and hypothermia in rats, but unlike other 5-HT agonists, does not induce 5-HT stereotypy even at high doses (10 mg/kg sc). LY165163 (1 mg/kg) increased striatal DOPA accumulation in animals treated with the aromatic amino acid decarboxylase inhibitor 3-hydroxy-benzylhydrazine (NSD 1015) (100 mg/kg ip). This increase was also found when the drug was given to animals pretreated with parachlorophenylalanine (pCPA) (150 mg/kg ip daily for 3 days). LY165163 (2 and 4 mg/kg sc) inhibited stereotyped behaviour induced by the dopamine (DA) agonist apomorphine (2 mg/kg sc). LY165163 (2, 4, 10 mg/kg sc) also inhibited stereotyped components of the 5-HT syndrome induced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT; 5 mg/kg ip) which previous studies (e.g. Andrews et al. 1982) suggested to require DA (head weaving, reciprocal forepaw treading). Thus, while other 5-HT1A agonists such as 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) cause stereotypy, this does not occur with LY165163, probably because the drug blocks DA receptors.
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PMID:Blockade of dopamine receptors explains the lack of 5-HT stereotypy on treatment with the putative 5-HT1A agonist LY165163. 295 21

The putative 5-HT1A agonist 1-[2-(4-aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine (LY165163, PAPP) (1, 2, 4, 10 mg/kg s.c.) caused a significant and dose-dependent hypothermia in rats, 30 and 60 min after injection. The decreases of temperature were less marked than that caused by 8-OH-DPAT 1 mg/kg s.c.). Depletion of brain serotonin (5-HT) by 91% following pretreatment with p-chlorophenylalanine (pCPA) (150 mg/kg i.p. on three successive days) significantly enhanced the hypothermic effects of both 8-OH-DPAT (0.25 mg/kg s.c.) and LY165163 (4 mg/kg s.c.). LY165163-induced hypothermia was also somewhat enhanced following depletion of hypothalamic 5-HT by 76% after infusion of 5,7-dihydroxytryptamine (5,7-DHT) (150 micrograms) into the third ventricle. Results indicate that the hypothermia induced by the putative 5-HT1A agonists LY165163 and 8-OH-DPAT in the rat is not dependent on presynaptic 5-HT stores and is therefore probably mediated by postsynaptic 5-HT receptors.
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PMID:Hypothermia induced by the putative 5-HT1A agonists LY165163 and 8-OH-DPAT is not prevented by 5-HT depletion. 296 83

The effects of the serotonergic antagonist cyproheptadine and the agonist 1(m-chlorophenyl) piperazine (mCPP) on core body temperature, locomotor activity and operant responding for a water reward were determined in two lines of Sprague-Dawley rats selectively bred for differences in sensitivity to the anticholinesterase, diisopropyl fluorophosphate (DFP). Both cyproheptadine and mCPP induced a dose-dependent hypothermia that was significantly greater in the line of rat more sensitive to DFP (the Flinders Sensitive Line--FSL). On the other hand, the mild stimulant effects of cyproheptadine on operant responding and locomotor activity were similar in the two lines, whereas the marked inhibitory effects of mCPP on these two measures were significantly greater in the FSL rats. This study also confirmed that the FSL rats were significantly more sensitive to the hypothermic effects of oxotremorine, a muscarinic agonist, and showed that pretreatment with cyproheptadine reduced the hypothermic effects of oxotremorine to a similar extent in the two lines. These findings indicate that rats selectively bred for increased cholinergic function (FSL) also differ in their sensitivity to serotonergic agonists and antagonists, thereby extending the evidence for cholinergic-serotonergic interactions in the rat.
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PMID:Selective breeding for increased cholinergic function: increased serotonergic sensitivity. 324 12

The anticonvulsant effect of a series of 6-alkoxy-N,N-disubstituted-2-pyridinamines is described. An investigation was carried out to optimize the activity/side-effect ratio in this series of compounds. The most desirable profile was seen with 1-[6-(2-methylpropoxy)-2-pyridinyl]piperazine, 6, and this compound was selected for a more complete pharmacological evaluation. Overall, 6 has a pharmacological profile that is very similar to that of diphenylhydantoin (phenytoin). While nearly equipotent to phenytoin, animal studies suggest a fairly short duration of action. In addition, 6 exhibited some troublesome side effects including central nervous system depression and hypothermia.
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PMID:6-Alkoxy-N,N-disubstituted-2-pyridinamines as anticonvulsant agents. 359 26

This work represents the design, synthesis, and pharmacological testing of 4-phenylquinoline derivatives as potential antidepressants. Various modifications of substituents at the 2-position of the quinoline ring were tried, and two main series of derivatives were synthesized. In the first series, an open (dialkylamino)alkyl chain is linked to the 2-position of the quinoline ring by isosteres. The second approach involved the synthesis of a novel analogue of trazodone with a 4-phenylquinoline grouping replacing the chlorophenyl group of trazodone. The potential antidepressant activity of these new compounds has been demonstrated by their antagonism to the reserpine-induced hypothermia in mice. Both length of the side chain and isosteric displacements within the side chain affect the value of the ED50 obtained. Compounds having three atoms separating the terminal nitrogen from the quinoline ring were found to be more active than those with four atoms. The 2-thia derivatives were devoid of antidepressant activity. Replacement of the open side chain at the 2-position of the quinoline ring by piperazine or substituted piperazines resulted in new compounds that are slightly more potent than imipramine.
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PMID:Design, synthesis, and pharmacological activities of 2-substituted 4-phenylquinolines as potential antidepressant drugs. 404 18

Pirenperone, an antagonist of 5-HT2 but not 5-HT1 receptors, has been studied for its central antiserotonergic and antidopaminergic activity. Pirenperone (0.00525-0.1 mg/kg) antagonized dose-dependently stimulation of the hind limb flexor reflex in spinal rats induced by LSD, quipazine or fenfluramine, and hyperthermia induced by serotonin (5-hydroxytryptamine; 5-HT)-like drugs (1-5-hydroxytryptophan, fenfluramine, p-chloroamphetamine, 1-/m-chlorophenyl/-piperazine, quipazine) in heat-adapted rats. Pirenperone also counteracted tryptamine-induced convulsions in rats (ID50 = 0.87 mg/kg); however, this action was weaker than that of metergoline (ID50 = 0.22 mg/kg). Pirenperone (0.1-1.6 mg/kg) produced sedation in mice and rats, and-in doses of 0.4-6.4 mg/kg-catalepsy in rats. Given in doses ranging from 0.1 to 1.6 mg/kg, pirenperone antagonized d-amphetamine-induced locomotor hyperactivity in mice and rats, the hyperactivity induced by apomorphine in rats, apomorphine- or d-amphetamine-induced stereotypy in rats and stimulation of the hind limb flexor reflex induced by the alpha-adrenoceptor agonist-clonidine. Pirenperone (6.4 mg/kg) significantly attenuated apomorphine (1 mg/kg)-induced hypothermia in mice. The results obtained indicate that pirenperone may be regarded as a relatively specific antagonist of the 5-HT2 receptor only when it is employed in very low doses (less than 0.1 mg/kg). Used in higher doses (greater than 0.1 mg/kg), it behaves like a typical neuroleptic, i.e. like a dopamine antagonist with antiserotonergic, antitryptaminergic and antiadrenergic properties.
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PMID:Central antiserotonergic and antidopaminergic action of pirenperone, a putative 5-HT2 receptor antagonist. 404 12


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