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)

GK 13 (N-[1-(2-benzo (b) thiophenyl)-cyclohexyl] piperidine), GBR 12783 (1-[2-(diphenylmethoxy)-ethyl] 4-(3-phenyl propenyl)-piperazine and dexamphetamine are three indirect catecholaminergic agonists, acting via different neurochemical mechanisms. We have compared their effects in rodents, in several behavioral tests. All three drugs increased locomotion. The stimulant locomotor effect of dexamphetamine was more easily antagonized by haloperidol than that of GBR 12783 and GK 13. Only dexamphetamine reversed reserpine-induced akinesia. This reversal was prevented by pretreatment with either GK 13 or GBR 12783. The three drugs reduced pentobarbital sleeping time in mice. They induced rotation ipsilateral to a unilateral 6-OHDA lesion of the nigrostriatal dopaminergic pathway. The stereotypies induced by GK 13 and GBR 12783 were essentially limited to sniffing. Haloperidol-induced catalepsy was apparently more easily antagonized by dexamphetamine than by GK 13 or GBR 12783. GK 13 and GBR 12783 had no significant effects on body temperature. The three drugs displayed an anti-immobility effect in the "despair test". Dexamphetamine and GK 13 reversed the hypothermia induced by apomorphine (16 mg/kg), as well as reserpine-induced hypothermia and reserpine-induced ptosis. Dexamphetamine induced a dose-dependent anorectic effect, whereas GK 13 and GBR 12783 induced only a brief and partial anorexia. Similar observations were made on water intake. Pretreatment with either GBR 12783 or GK 13 did not affect the dexamphetamine-induced anorexia. Effects of the three drugs are discussed by reference to their known neurochemical properties on catecholaminergic transmission.
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PMID:Comparison of the effects of three indirect dopamine agonists, GK 13, GBR 12783 and dexamphetamine on behavioural tests involving central catecholaminergic transmissions. 197 95

Triadimefon is a widely used systemic fungicide, yet there is little published information on its effects in mammals. This study describes the effects of triadimefon in male and female rats using a functional observational battery (FOB), motor activity (measured in a figure-eight maze), and operant performance (responding under a fixed-interval 3-min schedule). For the FOB, Long-Evans hooded rats were tested immediately before dosing and 0.5, 4, 24, and 48 hr after IP dosing with either vehicle, 30, 100, or 300 mg/kg triadimefon. Prominent effects of triadimefon (100 and 300 mg/kg) included increased arousal, stereotypies involving repetitive sniffing, head bobbing, and pacing, and self-mutilation. Dose-related handling-induced convulsions, changes in reflexes and sensory reactivity, hypothermia, and body weight loss were also significant findings. Doses of 30, 75 and 150 mg/kg triadimefon increased figure-eight maze activity whereas 300 mg/kg decreased activity. Habituation of activity during the session as well as the spatial distribution within the maze were also affected by triadimefon. Overall rates of responding maintained by fixed-interval milk reinforcement were increased at 30 and 56 mg/kg, and decreased at 100 and 200 mg/kg. Responding within the 3-min fixed-interval was also affected, with low rates normally occurring early in the interval markedly increased. These effects on operant performance were similar to those seen following d-amphetamine, and were attenuated by pretreatment with chlorpromazine (0.5 mg/kg). On many measures, female rats appeared to be somewhat more sensitive than males. Recovery was evident in some measures the day after dosing, but the effects of high doses (greater than or equal to 100 mg/kg) were typically prolonged (several days). Thus triadimefon produced a unique neurotoxic syndrome which is similar in many aspects to that produced by CNS stimulants.
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PMID:Neurobehavioral effect of triadimefon, a triazole fungicide, in male and female rats. 275 25

The effect of various doses of apomorphine (APO) (25, 250, 400 and 750 micrograms/kg, s.c.) on open field behaviour, stereotyped behaviour, body temperature and concentrations of serum oestradiol was studied in cycling females and in ovariectomized rats. With the exception of grooming, the hormonal variations during the cycle, or the ovariectomy, did not have an effect on behaviour related to stimulation of presynaptic dopamine (DA) receptors. The endocrine status on proestrus (PE), characterized by an increase in serum oestradiol, did influence hyperlocomotion and hypothermia induced by apomorphine; the former being attenuated and the latter increased, as compared to the other phases of the cycle. Ovariectomy resulted in an increase in the stimulatory effect of apomorphine on locomotion. Stereotypy induced by apomorphine was unaltered by hormonal variations during the cycle and it was slightly attenuated by removal of the ovaries. During phases of low levels of oestrogen (oestrus, metestrus) apomorphine significantly increased the levels of serum oestradiol, determined 30 min after the administration of drug. It is concluded that the various DAergic mechanisms in brain are differentially affected by hormonal variations during the cycle and by ovariectomy.
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PMID:Apomorphine-induced behaviour during the oestrous cycle of the rat. 365 16

2-N,N-dipropylamino 5,6-dihydroxytetralin (nPr2 ADTN), a potent dopaminergic agonist, induces the same polyphasic effects observed with apomorphine by Protais et al., (1983). The dose related sequence of behaviours in mice can be summed up as followed: to 0.9 to 3.9 micrograms.kg-1, a decrease in motor activity without any other effects; to 7.8 to 15.6 micrograms.kg-1, a return to control level or an increase in motility alone according to experimental conditions; to 31 to 62.5 micrograms.kg-1, a second phase of hypomotility when hypothermia develops; above 125 micrograms.kg-1, a second phase of hypermotility when both stereotypies and climbing behaviour appear. Hypothermia moreover, disappears. The effects of the nPr2 ADTN were compared with those of apomorphine obtained in others studies (Puech et al., 1974; Protais et al., 1983). The tetralin derivative differs from apomorphine in that the first phase of hypermotility it induces is greater, and that hypothermia disappears at high doses.
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PMID:Dose related sequence of effects induced by the DA agonist 2-(N,N-dipropyl)-amino-5,6-dihydroxytetralin. 371 99

The effects of enantiomers of nomifensine were compared in five psychopharmacological tests in which (+/-)-nomifensine is active. In mice, (+)-nomifensine increased motor activity at 16 mg/kg, 8 mg/kg reduced the hypothermia and ptosis induced by reserpine and antagonized the hypothermia induced by 16 mg/kg of apomorphine. (+)-Nomifensine 4 mg/kg potentiated yohimbine toxicity. (-)-Nomifensine 4,8, or 16 mg/kg was inactive in all these tests. In rats, (+)-nomifensine 8 mg/kg induced stereotyped movements whereas (-)-nomifensine 64 mg/kg did not produce stereotypies.
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PMID:Psychopharmacological effects of nomifensine enantiomers. 404 12

2-Bromolisuride (2-Br-LIS), a derivative of the ergot dopamine (DA) agonist lisuride, was investigated in rodents in comparison with the DA antagonist haloperidol with regard to its influence on DA related behaviour, cerebral DA metabolism and prolactin (PRL) secretion. 2-Br-LIS produced catalepsy in mice (ED50 3.3 mg/kg i.p.), antagonized apomorphine-induced stereotypies in mice (ED50 0.4 mg/kg i.p.), antagonized DA agonist-induced stereotypies in rats (0.1-1.56 mg/kg i.p.), inhibited locomotor activity in rats (0.025-6.25 mg/kg i.p.), antagonized the hyperactivity produced by various DA agonists in rats (0.025-6.25 mg/kg i.p.) and inhibited the apomorphine-induced hypothermia in mice (0.05-0.78 mg/kg i.p.). 2-Br-LIS (0.03-10 mg/kg i.p.) stimulated DA biosynthesis and DOPAC formation in the striatum and DA rich limbic system of rats, but had no effect on serotonin turnover. In striatum and limbic forebrain of gamma-butyrolactone-pretreated rats 2-Br-LIS reversed the apomorphine-induced inhibition of DOPA accumulation. 2-Br-LIS (0.03 - 3 mg/kg) enhanced PRL secretion in intact male rats. These findings indicate DA antagonistic properties of 2-Br-LIS presumably due to blockade of central pre- and postsynaptic DA receptors being of approximately the same order of potency as haloperidol. 2-Br-LIS is the first ergot compound with definite antidopaminergic properties suggesting its potential usefulness as a neuroleptic.
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PMID:Central antidopaminergic properties of 2-bromolisuride, an analogue of the ergot dopamine agonist lisuride. 660 92

The effects of various doses of estrogen on apomorphine (Apo)-induced hypothermia and stereotypy were investigated in ovariectomized rats. Daily administration of estradiol (5, 15 or 100 micrograms/kg) for 4 days or estradiol (100 micrograms/kg) for 3 days, followed by 4 and 72 hr withdrawal periods respectively, had no effect on apomorphine-induced hypothermia or stereotypy in a cold (4 degrees C) environment, although both effects were blocked by haloperidol. Large doses of estradiol (100 micrograms/kg) given for 3 days, followed by either 24 or 72 hr withdrawal, slightly attenuated apomorphine-induced stereotypy at 22 degrees C. Stereotypy observed at 22 degrees C was of greater magnitude than that seen at 4 degrees C. The results indicate that although high, non-physiological levels of estrogen may attenuate striatal-dependent stereotypies, this hormone has no detectable influence on dopaminergic mechanisms in the preoptic-anterior hypothalamic regions that are thought to mediate apomorphine-induced hypothermia.
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PMID:The effects of estrogen on apomorphine-induced hypothermia and stereotypy in the rat. 668 92

One major mechanism underlying the central action of neurotensin is an interaction with the function of dopamine (DA)-containing neurons. In addition, direct or indirect DA agonists have been reported to promote neurotensin release. We have found that SR 48692, a non-peptide neurotensin receptor antagonist (0.04-0.64 mg/kg orally), antagonizes (50-65%) yawning induced by apomorphine (0.07 mg/kg SC) or bromocriptine (2 mg/kg IP) in rats, and turning behaviour induced by intrastriatal injection of apomorphine (0.25 micrograms), (+) SKF 38393 (0.1 micrograms), bromocriptine (0.01 ng) or (+) amphetamine (10 micrograms) in mice. Other apomorphine-induced effects in mice and rats such as climbing, hypothermia, hypo- and hyper-locomotion, penile erections and stereotypies were not significantly modified by SR 48692. Taken together, these data suggest that neurotensin may play a permissive role in the expression of some but not all behavioural responses to DA receptor stimulation.
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PMID:Effects of SR 48692, a selective non-peptide neurotensin receptor antagonist, on two dopamine-dependent behavioural responses in mice and rats. 786 53

Neurotensin, an endogenous peptide widely distributed throughout the brain, fulfils neurotransmitter criteria. When administered centrally, neurotensin induces various effects and modulates the activity of the mesolimbic dopamine system. It antagonizes the behavioural action of dopamine in a manner similar, but not identical, to antipsychotic drugs. Neurotensin is even considered to be an endogenous neuroleptic. In fact, microinjection of neurotensin elicits different effects depending on both the dose and the cerebral structures into which the injection is made. Our work on the development of orally-active neurotensin antagonists has led to the identification of SR 48692, the first non-peptide antagonist of the neurotensin receptor, and some analogues. This small molecule reveals a surprising neuropharmacological profile. It antagonizes turning behaviour induced in mice and rats (after striatal or ventral tegmental area administration of neurotensin, respectively), hypolocomotion induced by intracerebroventricular injection of neurotensin in rats, and reverses the inhibitory effect of neurotensin (nucleus accumbens injection) on amphetamine-induced hyperlocomotion in rats. However, SR 48692 cannot reverse either dopamine release in the nucleus accumbens evoked by neurotensin injection in ventral tegmental area, or hypothermia and analgesia induced by intracerebroventricular injection of neurotensin. As direct and indirect dopamine agonists have been reported to promote neurotensin release in the cortex, behavioural studies were performed using injection of apomorphine. In these experiments, SR 48692 inhibited only turning and yawning. It did not antagonize other apomorphine-dependent effects such as climbing, hypothermia, hypo- or hyperlocomotion, penile erection and stereotypies. All together, these data raise the question of the existence of neurotensin receptor subtypes and confirm that the nature of neurotensin and dopamine interactions depends on the brain structures considered.
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PMID:Neuropharmacological profile of non-peptide neurotensin antagonists. 880 71

Amisulpride, a benzamide derivative, is an antipsychotic drug with a pharmacological profile distinct from that of classical neuroleptics such as haloperidol and from that of another benzamide, remoxipride. In mice, amisulpride antagonized hypothermia induced by apomorphine, quinpirole or (+/-) 7-hydroxy-2-(di-n-propylamino)-tetralin, an effect involving D2/D3 receptors, at similar doses (ED50 approximately 2 mg/kg i.p.), which were much lower than doses that blocked apomorphine-induced climbing, an effect involving postsynaptic D2 and D1 receptor activation (ED50 = 21 mg/kg i.p.). Much higher doses (ED50 = 54 mg/kg i.p.) of amisulpride were needed to block grooming behavior observed after a short period in water, a D1 receptor-mediated behavior. In rats, amisulpride preferentially inhibited effects produced by low doses of apomorphine (hypomotility and yawning), related to stimulation of presynaptic D2/D3 dopamine autoreceptors (ED50 = 0.3 and 0.19 mg/kg i.p.). By contrast, amisulpride antagonized apomorphine-induced hypermotility, a postsynaptic dopamine receptor-mediated effect, at a much higher dose (ED50 = 30 mg/kg i.p.). Amisulpride (100 mg/kg i.p.) only partially inhibited apomorphine-induced stereotypies (gnawing) and had no effect on stereotypies induced by d-amphetamine. However, d-amphetamine-induced hyperactivity was antagonized by doses of amisulpride as low as 3 mg/kg i.p., which may indicate selectivity of this drug for limbic dopaminergic mechanisms. In addition, in contrast to haloperidol or remoxipride, which produced catalepsy at doses 2 or 3 times higher than those that antagonized stereotypies induced by apomorphine, amisulpride did not induce catalepsy up to a dose of 100 mg/kg i.p., which occupies 80% of striatal D2 receptors. This pharmacological profile of amisulpride, characterized by a preferential blockade of effects involving presynaptic mechanisms and limbic structures, may explain the clinical efficacy of this drug against both negative and positive symptoms of schizophrenia and its low propensity to produce extrapyramidal side effects.
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PMID:Psychopharmacological profile of amisulpride: an antipsychotic drug with presynaptic D2/D3 dopamine receptor antagonist activity and limbic selectivity. 899 84


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