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)

A new benzamide, cis-N-(1-benzyl-2-methylpyrrolidin - 3 - yl) - 5 - chloro - 2 - methoxy - 4 - methylaminobenzamide (YM-09151-2) exhibited more potent and longer-lasting inhibitory effects on apomorphine-induced behaviours (stereotyped behaviour, emesis and hypothermia), and methamphetamine-induced stereotyped behaviour, conditioned avoidance response and open field behaviour, conditioned avoidance response and open field behaviour than either structurally similar benzamides (YM-0850 and sulpiride) or classical neuroleptics [chlorpromazine (CPZ) and haloperidol(HPD)]. Such inhibitory effects of YM-09151-2 relative to cataleptogenicity were greater than those of CPz and HPD. In contrast, sulpiride elicited few of the neuroleptic effects described above. YM-09151-2, a potent inhibitor for dopamine-sensitive adenylate cyclase (Ki: 3.0 nM) reduced, in a selective manner, the binding of [3H]dopamine to the dopamine D1 receptor (Ki:4.8 nm) associated with adenylate cyclase rather than to the dopamine D2 receptor (Ki: 0.98 microM) independent of adenylate cyclase. Sulpiride, on the contrary, inhibited only the binding to the dopamine D2 receptor, CPZ and HPD antagonized [3H]dopamine nonselectively at the two distinct dopaminergic receptors. These results suggest that YM-09151-2 is a potent and long-lasting neuroleptic with a highly selective blocking action on the dopamine D1 receptor.
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PMID:Neuroleptic properties of cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylaminobenzamide (YM-09151-2) with selective antidopaminergic activity. 611 70

Clozapine (7.5-30.0 mumol kg-1 s.c.) produced a decrease in core temperature in the rat. The temperature decrease caused by clozapine (7.5 mumol kg-1 s.c.) was fully antagonized by the selective dopamine D1 receptor antagonist SCH 23390 (0.3 mumol kg-1) s.c.) and a partial antagonism was obtained by the selective dopamine D2 receptor antagonist raclopride (1.6 mumol kg-1 s.c.). On the other hand, the hypothermia was not antagonized by alpha-adrenoceptor antagonists (idazoxan and prazosin), 5-HT receptor antagonists ((-)-pindolol and ritanserin) or by the muscarinic M1 receptor antagonist scopolamine. The hyperthermia produced by the 5-HT1C/2 receptor agonist DOI (0.75 mumol kg-1) was blocked by clozapine (3.0 mumol kg-1 s.c.). Clozapine did not antagonize hypothermia produced by selective dopamine D1 and D2 receptor agonists (A 68930 and quinpirole), the alpha 2-adrenoceptor agonist clonidine, the 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) or the muscarinic M1 receptor agonist oxotremorine. The present results suggest that clozapine may be a partial agonist at brain dopamine D1 receptors.
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PMID:Antagonism by SCH 23390 of clozapine-induced hypothermia in the rat. 791 99

In the present work, the effects of neurotransmitter antagonists on theophylline-induced changes in body temperature were investigated. Intraperitoneal (i.p.) administration of a low dose of theophylline (25 mg/kg) induced slight hyperthermia, while high doses (75 and 100 mg/kg) induced hypothermia. The hypothermic effect of theophylline was decreased by pretreatment of animals with the dopamine D2 receptor antagonists sulpiride (15 and 30 mg/kg i.p.) and pimozide (0.125 and 0.25 mg/kg i.p.), the muscarinic receptor antagonist atropine (2.5 and 5 mg/kg i.p.) and the 5-HT receptor antagonist metergoline (0.25 mg/kg i.p.). However, the dopamine D1 receptor antagonist SCH 23390 (0.05 and 0.5 mg/kg i.p.), the alpha-adrenoceptor antagonist phenoxybenzamine (2.5 and 5 mg/kg i.p.) and the beta-adrenoceptor antagonist propranolol (5 and 10 mg/kg i.p.) did not after the theophylline response. In reserpinized mice, theophylline caused a dose-dependent rise in body temperature. The response was blocked in animals pretreated with phenoxybenzamine, propranolol and atropine. Single treatment of animals with either SCH 23390 or sulpiride, and also with a combination of the two drugs, decreased the hyperthermia induced by theophylline in reserpinized mice. Pimozide or metergoline did not have any effect in this respect. These data suggest that the hypothermic response to theophylline may be mediated through dopaminergic, cholinergic and serotonergic mechanisms. The hyperthermic action of theophylline in reserpinized animals may be mediated through dopaminergic, cholinergic and adrenergic systems. Overall it seems likely that theophylline interacts with modulatory mechanisms involved in thermoregulation.
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PMID:On the mechanisms by which theophylline changes core body temperature in mice. 808 93

Administration of the selective dopamine D1 and D2 receptor agonists, A 68930 (0.9-60.0 mumol kg-1 s.c.) and quinpirole (0.1-6.0 mumol kg-1 s.c.), produced a dose-dependent decrease in core temperature in the rat. The hypothermia induced by quinpirole (1.5 mumol kg-1) was antagonized by pretreatment with the selective dopamine D2 receptor antagonist, raclopride (1.6 mumol kg-1 s.c.), but not by the dopamine D1 receptor antagonist, SCH 23390 (0.3 mumol kg-1 s.c.), whereas the hypothermia induced by A 68930 (3.8 mumol kg-1) was antagonized by SCH 23390 (0.3 mumol kg-1), but not by raclopride (1.6 mumol kg-1). Together, these results suggest that both dopamine D1 and D2 receptors are specifically involved in the regulation of body temperature in the rat.
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PMID:Evidence for specific involvement of dopamine D1 and D2 receptors in the regulation of body temperature in the rat. 810 71

1. The 5-hydroxytryptamine (5-HT)1A agonist 8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT) has been evaluated in a mouse model for detecting potential antidepressants (Porsolt test). The effects of various receptor antagonists, lesions of brain monoaminergic neurones and chronic drug treatments on this 8-OH-DPAT-induced response have also been determined. 2. 8-OH-DPAT (0.3-10.0 mg kg-1, s.c.) dose-dependently increased the mobility of mice in the Porsolt test. Other selective 5-HT1A receptor ligands (0.3-30 mg kg-1, s.c.) either mimicked the 8-OH-DPAT response (ipsapirone, at 10 and 30 mg kg-1, s.c.) or were inactive (buspirone and gepirone). However, each of these compounds (< or = 100 mg kg-1, p.o.) inhibited the response to 8-OH-DPAT (3 mg kg-1, s.c.) when given concurrently. 3. The putative 5-HT1A antagonists, spiroxatrine (1-30 mg kg-1, p.o.), (+/-)-pindolol (30 mg kg-1, p.o.) and methiothepin (3-10 mg kg-1, p.o.), each attenuated the 8-OH-DPAT (3 mg kg-1, s.c.)-induced increase in mobility. 4. The dopamine D1 receptor antagonist, SCH 23390 (3-10 mg kg-1, p.o.), weakly reversed the 8-OH-DPAT response. Antagonists at 5-HTlc/5-HT2 receptors (ketanserin; 0.1-3.0 mg kg-1, p.o.),5-HT3 receptors (ondansetron; 0.03-10mg kg-1, p.o.), at-adrenoceptors (prazosin; 1-3mgkg-1, p.o.),alpha2 -adrenoceptors (idazoxan; 3-30mg kg-1, p.o.), alpha 1-adrenoceptors (metoprolol; 1-30mgkg-1, p.o.),beta 2-adrenoceptors (ICI 118,551; 1-30 mg kg-1, p.o.), dopamine D2 receptors (sulpiride; 10-300mg kg-',p.o.) and opiate receptors (naloxone; 3-100 mg kg-', p.o.) had no effect on the 8-OH-DPAT response.5. Selective destruction of 5-HT neurones with 5,7-dihydroxytryptamine or inhibition of 5-HT synthesis with p-chlorophenylalanine did not change the 8-OH-DPAT response in the Porsolt test. This response was also unaltered by pretreatment with the noradrenergic neurotoxin, DSP-4.6. Administration of 8-OH-DPAT (3 mg kg-1, s.c.) twice-daily for 10 days attenuated the hypothermia,but not the increased mobility, induced by 8-OH-DPAT (3 mg kg-1, s.c.). Similarly, repeated administration of amitriptyline (3-30 mg kg-1), desipramine (3-30 mg kg-1) or dothiepin (10-100 mg kg-1) also attenuated the former, but not the latter, response.7. We conclude that 8-OH-DPAT produces an antidepressant-like effect in the Porsolt test which is mediated via postsynaptic 5-HT1A receptors.
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PMID:Mediation of the antidepressant-like effect of 8-OH-DPAT in mice by postsynaptic 5-HT1A receptors. 846 55

Clozapine (0.625-10.0 mg kg-1 s.c.), but not the two major clozapine metabolites, N-desmethylclozapine (0.625-10.0 mg kg-1 s.c.) or clozapine-N-oxide (0.625-10.0 mg kg-1 s.c.), caused a dose-dependent decrease in core temperature in the rat. Furthermore, the clozapine-induced hypothermia (2.5 mg kg-1 s.c.) was fully antagonised by pretreatment with the selective dopamine D1 receptor antagonist (+)-5-(2,3-dihydrobenzofuran-7-yl)-3-methyl-8-nitro-2,3,4, 5-tetrahydro-1 H-3-benzazepine-7-ol, maleate (NNC 687) (4.0 mg kg-1 s.c.). NNC 687 by itself (2.0-8.0 mg kg-1 s.c.) did not affect core temperature. The present results provide further evidence for the dopamine D1 receptor agonist properties of clozapine.
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PMID:Further evidence for clozapine as a dopamine D1 receptor agonist. 883 Nov

The present study investigated the effects of the cannabinoid receptor agonist CP 55,940 (1-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl) phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol) and the cannabinoid receptor antagonist SR 141716A (N-(piperidin-l-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1 H-pyrazole-3-carboxamide hydrochloride) on ultrasonic vocalizations, body temperature and activity in 11-13-day-old rat pups. Testing occurred in a 5-min session 30 min following drug administration. CP 55,940 produced a dose-dependent decrease in ultrasonic vocalizations, with a 1000-micrograms/kg dose causing an almost complete inhibition of calls. Doses of 100 and 1000 micrograms/kg of CP 55,940, but not 10 micrograms/kg, caused significant hypothermia in the pups and the 1000 micrograms/kg dose also inhibited activity. The cannabinoid receptor antagonist SR 141716A (20 mg/kg) reversed the effects of 1000 micrograms/kg CP 55,940 on ultrasonic vocalizations and body temperature, but the benzodiazepine receptor antagonist flumazenil (20 mg/kg), the dopamine D1 receptor antagonist SCH 23390 (0.5 mg/kg) and the opioid receptor antagonist naloxone (1 mg/kg) did not. When administered alone, SR 141716A (20 mg/kg) increased pup ultrasonic vocalizations without affecting body temperature or activity. These results indicate that cannabinoids modulate ultrasonic vocalization production in rat pups in a manner that is independent of hypothermia. The increase in ultrasonic vocalizations produced by SR 141716A is one of the first reported behavioural effects of this drug and suggests that the endogenous cannabinoid ligand anandamide may be involved in the regulation of ultrasonic vocalizations.
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PMID:Cannabinoid modulation of rat pup ultrasonic vocalizations. 890 27

The selective dopamine D1 receptor agonist dihydrexidine (2.0-8.0 mg/kg, s.c.) caused a dose-dependent decrease in core temperature in rats. The hypothermia produced by dihydrexidine (4.0 mg/kg), was completely blocked by the dopamine D1 receptor antagonists SCH 23390 (0.1 mg/kg, s.c.) or NNC 687 (4.0 mg/kg, s.c.), but not by the dopamine D2/3 receptor antagonist raclopride (0.2 mg/kg, s.c.). Neither of the dopamine antagonists by themselves produced any effects on core temperature. The present results provide important evidence for the notion that activation of dopamine D1 receptors induces hypothermia in rats.
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PMID:Dihydrexidine produces hypothermia in rats via activation of dopamine D1 receptors. 940 51

The present study was designed to examine a possible interaction between dopamine D1 and D2/3 receptors involved in thermoregulation in rats. The dose-dependent hypothermia produced by the dopamine D1 receptor agonist A 68930 (0.9-15.0 micromol kg-1, s.c.), was augmented in an additive manner by pretreatment with the dopamine D2/3 receptor agonist 7-OH-DPAT (0.06 micromol kg-1, s.c.). The dose-dependent hypothermia produced by 7-OH-DPAT (0.06-1.00 micromol kg-1 s.c.) was also augmented in an additive manner by pretreatment with A 68930 (0.9 micromol kg-1 s.c.). In contrast to these observations, locomotor activity measurements disclosed a marked interaction between the dopamine D1 and D2/3 receptor agonists. Thus, A 68930 (0.9-15.0 micromol kg-1, s.c.) produced a dose-dependent suppression of open-field locomotor activity. The addition of 7-OH-DPAT (1.00 micromol kg-1, s.c.), which by itself produced a weak suppression of locomotor activity, resulted in a gradual reversal of the A 68930-induced suppression of the locomotor activity. Thus, the present results provides strong support for an independent role of dopamine D1 receptors in rat thermoregulatory mechanisms, distinct from effects mediated via the dopamine D2 receptor family.
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PMID:Independent roles of dopamine D1 and D2/3 receptors in rat thermoregulation. 950 18

A large number of ligand binding studies have shown that clozapine has a number of receptor affinities, including those of the dopamine (DA) D1 and D2 receptor families. The study of intrinsic efficacy at these receptors is less straight-forward. In the experiments summarised here, evidence is presented that clozapine behaves as an agonist at DA D1 receptors. Thus, the hypothermia produced by clozapine (2.5 mg kg(-1)) in the rat is fully antagonised by either of the selective DA D1 receptor antagonists SCH-23390 (0.1 mg kg(-1)) or NNC-687 (4 mg kg(-1)). These results provide an intriguing explanation for the clinical profile of clozapine as an atypical antipsychotic drug. Thus, there are supporting clinical and laboratory observations implicating DA D1 receptors in the prefrontal cortex in cognitive functions. Finally, clozapine displays features with regard to extrapyramidal motor mechanisms, and seizure thresholds, that could be explained by its properties as a DA D1 receptor agonist.
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PMID:Clozapine: dopamine D1 receptor agonism in the prefrontal cortex as the code to decipher a Rosetta stone of antipsychotic drugs. 1036 74


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