Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

LB50016 was characterized as a selective and potent 5-HT1A receptor agonist and evaluate its anxiolytic and antidepressant activities. It shows high affinity for 5-HT1A receptor, moderate affinity for alpha 2 adrenergic and 5-HT2A receptors and no significant affinity for other receptors tested. Hypothermia and increased serum corticosterone level were observed in LB50016-treated rats, which are mediated mostly by post synaptic 5-HT1A receptor activation. In the mouse forced swim model for depression, LB50016-elicited dose-dependent reductions in immobility time, showing ED50 of approximately 3 mg/kg i.p., which was blocked by pretreatment of NAN-190, 5-HT1A antagonist. In face-to-face test for anxiolytic activity in mice, estimated ED50 was 2 mg/kg, i.p. In isolation-induced aggression test with mice, fifty-fold increases in latency to attack were observed at 30 min and last up to 4 h after LB50016 treatment (3 mg/kg, i.p.). Taken together, LB50016-induced pharmacological activities are mediated by activation of 5-HT1A receptors, offering an effective therapeutic candidate in the management of anxiety and depression in humans.
 ...
PMID:Pharmacological characterization of LB50016, N-(4-amino)butyl 3-phenylpyrrolidine derivative, as a new 5-HT1A receptor agonist. 1023 May 6

Rats were given a single dose of reserpine (5 mg/kg s.c.) and behavioural responses to agonists at 5-HT receptor subtypes compared with those of control animals 21 days later. The following effects of activating postsynaptic 5-HT1A receptors by the agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) were significantly increased: tail-flick, reciprocal forepaw treading, flat body posture. The hyperphagic effect of activating presynaptic 5-HT1A receptors by 8-OH-DPAT tended to increase and hypothermia on activating postsynaptic 5-HT1A sites tended to decrease. The hyperlocomotor effect of activating 5-HT1A sites also tended to decrease possibly as a result of a dependence of this response on the known depletion of catecholamines by reserpine. Head shakes on activating 5-HT2A receptors by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and two effects of activating 5-HT2C receptors by 1-(3-chlorophenyl) piperazine (mCPP) were significantly increased (hypophagia, anxiety) and a third effect, hypolocomotion tended to increase but hypophagia on activating postsynaptic 5-HT1B receptors by CP-94, 253 was significantly attenuated. The results are discussed with particular reference to altered 5-HT function in depression.
 ...
PMID:Effect of reserpine on behavioural responses to agonists at 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT2C receptor subtypes. 1046 92

Systemic administration of dl-tetrahydropalmatine (THP; 10-50 mg x kg(-1) intraperitoneally) produced a proportional decrease in both colonic temperature and release of hypothalamic serotonin (5-hydroxytryptamine (5-HT)) in rats at room temperature. The hypothermia was brought about by cutaneous vasodilation and decreased metabolism. The THP- induced hypothermia was significantly attenuated in rats with brain 5-HT depletion produced by control injection of 5,7-dihydroxytryptamine or in rats with 5-HT2A receptor activation produced by 1-(2,5-dimethoxy-4-iodophenyl) -2-aminopropane, or in rats with 5-HT1A receptor antagonist produced by (-)-pindolol. The results suggest involvement of serotoninergic antagonism in the THP-induced hypothermia in rats
 ...
PMID:The hypothermic effects of dl-tetrahydropalmatine in rats. 1171 Dec 13

Three series of new unsubstituted or 2-acyl 1,2,3,4-tetrahydro-beta-carbolines (THBC), connected to 1-(o-methoxyphenyl)piperazine by 2-, 3- or 4-membered alkylene spacer (3, 4 or 5, respectively) in position 9, were synthesized and their 5-HT1A/5-HT2A receptor affinities and functional in vivo activities were investigated. Radioligand binding studies showed that unsubstituted (a) and acyl (b-f) derivatives with prop-1,3-ylene (4) and particularly with but-1,4-ylene (5) spacer had a high 5-HT1A receptor affinity (Ki = 30-110 nM), whereas the 5-HT1A affinity of derivatives with ethylene spacer (3) was low. All those compounds (except 5c, Ki = 44 nM) did not distinctly bind to 5-HT2A receptors. The obtained results indicated that the length of an alkylene chain was a crucial parameter for determining 5-HT1A receptor affinities of the tested compounds, while acyl substituents in position 2 of THBC were not important for their 5-HTIA/5-HT2A activities. It was also demonstrated that the few selected compounds (4d, 5a-c and 5e) with the highest affinity (Ki up to 50 nM) for 5-HT1A receptors, administered at doses of 10-20 mg/kg, behaved like antagonists of postsynaptic 5-HT1A receptors, as they reduced the 8-OH-DPAT (5-HT1A agonist)-induced lower lip retraction and behavioral syndrome in rats. Moreover, 4d seemed to be an agonist of presynaptic 5-HT1A receptors, since the hypothermia induced by its administration was attenuated by WAY 100635 (5-HT1A antagonist). Compound 5c, 5-HT2A receptor ligand, demonstrated an antagonistic activity, as it inhibited the (+/-)DOI (5-HT2A agonist)-induced head twitches in mice. The obtained results of in vivo studies suggest that introduction of different acyl substituents in position 2 of THBC with propylene or butylene spacer between tricyclous and arylpiperazine moiety is insignificant for the postsynaptic 5-HTIA receptor activity of the compounds tested in vivo. On the other hand, only compound 5c with an acryloyl group and a butylene chain behaved like a 5-HT1A/5-HT2A antagonist.
 ...
PMID:2-H- and 2-acyl-9- [omega-[4-(2-methoxyphenyl)piperazinyl]-alkyl]-1,2,3,4-tetrahydro-beta-carbolines as ligands of 5-HT1A and 5-HT2A receptors. 1199 69

A series of new 1,3-dimethyl-7-phenylalkyl-8-[3-(4-phenyl-1-piperazinyl)propylamino]-purine-2,6-dione derivatives (10-16) was synthesized and their 5-HTIA and 5-HT2A receptor affinities were determined. It was found that compounds with the phenylpropyl substituent in position 7 of purine-2,6-dione (12, 14 and 16), or with phenylmethyl in position 7 and 2-OCH3 in the phenylpiperazine part (13) showed a distinct affinity for 5-HTIA receptors (Ki = 8-50 nM). No structural modifications resulted in 5-HT2A ligands, since the affinity of 10-16 for those receptors was insignificant (Ki = 115-550 nM). The new 5-HT1A receptor ligands (12-14, 16) were investigated in vivo to determine their functional activity at those receptors. In behavioral studies, 12-14 and 16 behaved like postsynaptic 5-HTIA receptor antagonists, since they reduced lower lip retraction and the behavioral syndrome induced by 8-OH-DPAT (5-HT1A receptor agonist) in rats. When given alone, none of the compounds investigated in vivo, mimicked 8-OH-DPAT activity in those tests. Derivative 12 did not affect the body temperature in mice, whereas 13, 14 and 16 decreased it. Furthermore, 12 did not change the hypothermia induced by 8-OH-DPAT, and the decrease in body temperature in mice induced by 13, 14 or 16 was not antagonized by WAY 100635 (5-HT1A receptor antagonist); hence in that model neither 12, 13, 14 nor 16 acted as antagonists or agonists, respectively, at presynaptic 5-HT1A receptors.
 ...
PMID:Synthesis, 5-HT1A and 5-HT2A receptor activity of new 1-phenylpiperazinylpropyl derivatives with arylalkyl substituents in position 7 of purine-2,6-dione. 1199 82

Effects of melatonin on both thermoregulatory responses and hypothalamic serotonin release were assessed in unanesthetized rats at three different ambient temperatures (Ta). Systemic administration of melatonin (30-120 mg/kg, i.p) caused a decrease in both colonic temperature and hypothalamic serotonin (5-HT) release in rats at both Ta 8 and 22 degrees C. The hypothermia was brought about by a decrease in metabolic rate at Ta 8 degrees C, whereas at Ta 22 degrees C the hypothermia was produced by both a decrease in metabolic rate and an increase in cutaneous temperature. However, in the heat (Ta 31 degrees C), neither thermoregulatory responses nor hypothalamic 5-HT release was affected by the same amount of administered melatonin. The melatonin-induced hypothermia and decreased 5-HT release in the hypothalamus were attenuated by selective depletion of brain 5-HT produced by intracerebroventricular injection of 5,7-dihydroxytryptamine. Furthermore, the melatonin-induced hypothermia was almost completely abolished by treatment with a 5-HT2A receptor agonist (DOI) or a 5-HT1A receptor antagonist [(-)-pindolol]. The data indicate that melatonin potentiates the 5-HT1A receptor activation in the hypothalamus and results in hypothermic effects which can be antagonized by the expected hyperthermic effect of DOI.
 ...
PMID:Melatonin potentiates 5-HT(1A) receptor activation in rat hypothalamus and results in hypothermia. 1212 81

The present study was attempted to investigate the effect of puerarin, an isoflavone compound isolated from Pueraria lobata, on both the basal body temperature and pyrogenic fever in unanesthetized, restrained rats. Intraperitoneal administration of puerarin or crude extracts of Pueraria lobata elicited hypothermia. Direct administration of a small amount of puerarin into the lateral cerebral ventricle produced the same extent of hypothermia. Systemic or central administration of puerarin causes a decrease in both colonic temperature and hypothalamic 5-HT efflux in rats. The puerarin-induced hypothermia and decreased 5-HT efflux in the hypothalamus were attenuated by selective depletion of hypothalamic 5-HT produced by intracerebroventricular injection of 5,7-dihydroxytryptamine. Furthermore, the puerarin-induced hypothermia was almost completely abolished by treatment with a 5-HT2A-receptor agonist (DOI or quipazine) or a 5-HT1A-receptor antagonist [(-)-pindolol]. A 5-HT2A-receptor antagonist (ketanserin) or a 5-HT1A-receptor agonist (8-OH-DPAT) had additive effects with puerarin. Intracerebroventricular administration of interleukin-1 caused an increase in both colonic temperature and hypothalamic 5-HT efflux. The interleukin-1-induced hyperthermia and increased 5-HT efflux in the hypothalamus were attenuated by treatment with systemic administration of puerarin. The data indicate that puerarin exerts its hypothermic and antipyretic effects by activating 5-HT1 receptor and/or antagonizing 5-HT2A receptors in the hypothalamus.
 ...
PMID:Puerarin acts through brain serotonergic mechanisms to induce thermal effects. 1559 9

Two 1,2,4-substituted derivatives of piperazine were tested for their effect on dopamine and serotonin (5-HT) release in rat prefrontal cortex. Both compounds, 1-[4-(4-chinolin-2-yl-piperazin-1yl)-butyl]piperidin-2-on (MM5) and 1-[4-(2-methyl-4-chinolin-2-yl-piperazin-1-yl)-butyl]-8-azaspiro [4.5]decano-7,9-dion (MC1), produced hypothermia in mice and showed affinity for 5-HT1A receptors in-vitro. Like the selective 5-HT1A agonist 8-OH-DPAT (0.1 mg kg(-1)), MM5 given peripherally (30 mg kg(-1)) decreased the extracellular 5-HT level in rat prefrontal cortex, while MC1 suppressed 5-HT release at a higher dose (40 mg kg(-1)), but not at a lower one (30 mg kg(-1)). The effect of both compounds on 5-HT release was abolished by WAY 100635 (0.3 mg kg(-1)). MC1 (30 and 40 mg kg(-1)), but not MM5, raised cortical dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and extracellular homovanillic acid (HVA) levels. The effect of MC1 on dopamine release was reversed by neither WAY 100635 nor the non-selective 5-HT2 antagonist ritanserin (2 mg kg(-1)). However, ritanserin prevented the effect of the higher dose of MC1 on 5-HT release. The results of this study suggest that MM5 exhibits the profile of a 5-HT1A agonist devoid of dopaminergic activity. MC1 seems to possess moderate agonist activity at 5-HT1A and 5-HT2A receptors, while acting on 5-HT release in the rat prefrontal cortex. However, the facilitation of dopamine release by this compound does not seem to be related to its affinity for 5-HT1A and 5-HT2A receptors.
 ...
PMID:In-vivo effects of the 1,2,4-piperazine derivatives MM5 and MC1, putative 5-HT agonists, on dopamine and serotonin release in rat prefrontal cortex. 1572 Jul 84

Serotonin syndrome commonly follows irreversible monoamine oxidase (MAO)-inhibition and subsequent serotonin (5-HT) substrate (in rats with fore paw treading, hind limbs abduction, wet dog shake, hypothermia followed by hyperthermia). A stable gastric pentadecapeptide BPC 157 with very safe profile (inflammatory bowel disease clinical phase II, PL-10, PLD-116, PL-14736, Pliva) reduced the duration of immobility to a greater extent than imipramine, and, given peripherally, has region specific influence on brain 5-HT synthesis (alpha-[14C]methyl-L-tryptophan autoradiographic measurements) in rats, different from any other serotonergic drug. Thereby, we investigate this peptide (10 microg, 10 ng, 10 pg/kg i.p.) in (i) full serotonin syndrome in rat combining pargyline (irreversible MAO-inhibition; 75 mg/kg i.p.) and subsequent L-tryptophan (5-HT precursor; 100 mg/kg i.p.; BPC 157 as a co-treatment), or (ii, iii) using pargyline or L-tryptophan given separately, as a serotonin-substrate with (ii) pargyline (BPC 157 as a 15-min posttreatment) or as a potential serotonin syndrome inductor with (iii) L-tryptophan (BPC 157 as a 15 min-pretreatment). In all experiments, gastric pentadecapeptide BPC 157 contrasts with serotonin-syndrome either (i) presentation (i.e., particularly counteracted) or (ii) initiation (i.e., neither a serotonin substrate (counteraction of pargyline), nor an inductor for serotonin syndrome (no influence on L-tryptophan challenge)). Indicatively, severe serotonin syndrome in pargyline + L-tryptophan rats is considerably inhibited even by lower pentadecapeptide BPC 157 doses regimens (particularly disturbances such as hyperthermia and wet dog shake thought to be related to stimulation of 5-HT2A receptors), while the highest pentadecapeptide dose counteracts mild disturbances present in pargyline rats (mild hypothermia, feeble hind limbs abduction). Thereby, in severe serotonin syndrome, gastric pentadecapeptide BPC 157 (alone, no behavioral or temperature effect) has a beneficial activity, which is likely, particular, and mostly related to a rather specific counteraction of 5-HT2A receptors phenomena.
 ...
PMID:Gastric pentadecapeptide BPC 157 effective against serotonin syndrome in rats. 1584 Apr 2

Most of typical and atypical neuroleptics belonging to various chemical groups produce a significant, dose-dependent increase in the brain tolerance to global ischemia. This activity of neuroleptics is related to their structure and exhibits no correlation with their antipsychotic properties. Therefore, the ability to increase the brain tolerance to global ischemia is an independent property of neuroleptics. The neuroprotective effect is also not correlated with their affinity to serotonin 5-HT2A and dopamine D2 receptors, but is closely related to the development of deep hypothermia. Thermoneutral conditions prevent both effects. Tolerant strategy plays the main role in the development of the neuroprotective effect of neuroleptics.
 ...
PMID:[Neuroprotective effect of antipsychotic drugs (neuroleptics) in global brain ischemia]. 1699 32


<< Previous 1 2 3 4 Next >>