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)

The tripeptide, prolyl-leucyl glycine amide, a melanocyte-stimulating hormone inhibitory factor (MIF-I), which has been reported to be effective in improving symptoms of Parkinson's disease, has been compared with drugs known to activate dopamine receptors in rat and mouse brain. Unlike apomorphine, amphetamine and amantadine it was incapable of producing sterotyped behaviour in the rat and unlike 1-dopa it was also ineffective in rats pretreated with the monoamineoxidase inhibitor mebanazine. Neither did it potentiate apomorphine nor amphetamine in this test. MIF-I did not antagonise chlorpromazine-induced loss of locomotor activity in mice, an effect which was antagonised by apomorphine, amphetamine and amantadine. Chlorpromazine hypothermia in the mouse was antagonised by 1-dopa but not by MIF-I; similar findings were obtained in reserpine-pretreated mice. These results suggest that the reported beneficial effect of MIF-I in Parkinson's disease is unlikely to be due to an interaction with dopamine systems in the brain.
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PMID:A comparison between a melanocyte-stimulating hormone inhibitory factor (MIF-I) and substances known to activate central dopamine receptors. 0 32

Pharmacological properties of 2 amino-4-[4-(2-hydroxyethyl)-piperazin-1-yl]-6-trifluoromethyl-s-triazine (TR-10) were investigated in mice and rats. Chlorpromazine served as a reference compound. Tr-10 expressed in general the pharmacological profiles as neuroleptic ascertained by anti-methamphetamine activity, supression of conditioned avoidance response, taming effects, decrease in exploratory behavior and cataleptogenic activity. Among these effects, anti-methamphetamine action was most potent. Different from chlorpromazine, TR-10 showed a similar pharmacological activity pattern in the intraperitoneal and oral routes of administration as depicted from ED50/LD50 values. Although the effects relevant to neuroleptics were less potent than chlorpromazine, such were seen with TR-10 at lower doses than those causing muscle relaxation. TR-10 significantly depressed the spontaneous motor activity but showed no anti-convulsant action in mice. Hypothermic action, potentiating effects of hypnotics and alpha-adrenergic blocking action, characteristic to chlorpromazine, were very weak for TR-10. TR-10 also showed low toxicity in mice (LD50 = 820 mg/kg p.o., 465 mg/kg i.p.) compared with that of chlorpromazine (LD50 = 370 mg/kg p.o., 228 mg/kg i.p.).
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PMID:Pharmacological studies on triazine derivatives V Sedative and neuroleptic actions of 2-amino-4-[4-(2-hydroxyethyl)-piperazin-1-yl]-6-trifluoromethyl-s-triazine (TR-10). 1 93

Hypothermic effects of d-Amphetamine, chlorpromazine, a variety of other phenothiazines, ET495 and haloperidol in rats at 4 degrees C were measured separately and in combination. All the drugs produced some hypothermia. Among the phenothiazines, degree of hypothermia induced was found to be correlated with relative effectiveness of the drug as an antipsychotic agent. Hypothermic effects of each of the phenothiazines in combination with d-Amphetadrugs as an antipsychotic agent. Hypothermic effects of each of the phenothiazines in combination with d-Amphetamine was greater than for either drug alone. Hypothermic effects of the combination CPZ with Amphetamine was potentiated by haloperidol but blocked by ET495. The evidence supports a model of neuronal feedback loops either within the central DA mesolimbic pathway or between the mesolimbic and nigrostriatal DA systems. The establishment of interdependency between antipsychotic and hypothermic effects of phenothiazines offers promise not only to a greater understanding of the mechanisms underlying these effects, but the possibility of an objective test for screening new materials for antipsychotic effectiveness.
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PMID:The possible role of dopamine in phenothiazine-induced hypothermia in rats: an application to DA hypothesis of schizophrenia. 1 69

Intraperitoneal administration of a peripheral decarboxylase inhibitor benserazide (Ro4-4602) to unanesthetized rats produced alterations in body temperature which depended on ambient temperature. In the cold, hypothermia was brought about by a decrease in metabolic heat production. At room temperature, a dose-dependent hypothermia was preceded by a slight hyperthermia. The hypothermia was due to an increase in skin temperature (tail) and a decrease in metabolic heat production, while the hyperthermia was due to a decrease in skin temperatures (both tail and footsole) and an increase in metabolic heat production. In the heat, hyperthermia responses to benserazide were associated with decrease in skin temperature (both tail and footsole). Benserazide treatment produced no significant change in brain 5-HT content. Chlorpromazine-induced hypothermia was greatly enhanced after pretreatment of the animals with benserazide at room temperature (22 degrees).
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PMID:The effects of a decarboxylase inhibitor, benserazide, on both thermoregulation and chlorpromazine-induced hypothermia in rats. 3 39

Mescaline (25 mg/kg; 66 muc/kg) was injected (ip) in mice 45 min before chlorpromazine (CPZ, 2.5, 5, 15 mg/kg), thioridazine (10, 30, 45 mg/kg), or chlorpromazine-sulfoxide (CPZ-SO, 15 mg/kg). Excitement, agitation, slight increase in ventilation and occasional head-shaking were seen 30 min after mescaline and continued for 30-45 min thereafter; locomotor activity and the number of scratching events were significantly increased during this period. CPZ (2.5, 5, 15 mg/kg) and thioridazine (10, 30, 45 mg/kg) partially or completely blocked mescaline-induced gross behavior; CPZ-SO (15 mg/kg) was not effective. Increased scratching responses and locomotor activity induced by mescaline were antagonized by all doses of CPZ and thioridazine; at higher doses, both CPZ (7.5, 15 mg/kg) and thioridazine (45 mg/kg) induced cataleptic-like condition and marked hypothermia. Tissue levels of mescaline, examined 3 hr after its administration, were increased by all doses of CPZ and a higher dose of thioridazine (45 mg/kg); CPZ-SO and lower doses of thioridazine had no effect.
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PMID:Interaction of mescaline with phenothiazines: effect on behavior, body temperature, and tissue levels of hallucinogen in mice. 24 33

Hypothermia produced by IV administration of chlorpromazine (CPZ, 0.5-2.0 mg/kg) in a thermoneutral environment was greater in rabbits 2-4.5 years old than in animals under 24 months of age. One microgram CPZ given intracerebroventricularly (ICV) produced greater hypothermia in the older animals in tests performed in a thermoneutral environment while 0.25 and 0.5 microgram doses did not. The hypothermogenic effect of all three ICV doses of CPZ was enhanced in older rabbits exposed to cold. The brain of the older rabbit appears to be more sensitive to the hypothermogenic effects of CPZ. The findings suggest that this widely used tranquilizer can contribute to accidental hypothermia of the aged.
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PMID:Hypothermia produced by peripheral and central injections of chlorpromazine in aged rabbits. 48 19

The ability of neuroleptics to induce dopamine D2 receptor supersensitivity has been linked to the onset of tardive dyskinesia, the major side-effect of these drugs. Brain iron metabolism has been shown to be involved in the regulation of dopamine D2 receptors. We now examined the effect of chronic treatment with FeCl2 on chlorpromazine-induced D2 receptor supersensitivity. The results show that FeCl2 (5 mg/kg per day for 21 days) given to rats treated with chlorpromazine (10 mg/kg per day, for 21 days) prevented the onset of supersensitive biochemical and behavioral (apomorphine) expressions of DA D2 receptor. Inclusion of iron did not affect the chlorpromazine-induced sedation or hypothermia. Moreover, the combined chronic iron-chlorpromazine treatment produced the same net effects as chronic chlorpromazine on striatal amounts of dopamine, DOPAC (dihydroxyphenylacetic acid) and HVA (homovanillic acid). Chlorpromazine medication caused a decrease in liver non-haem iron levels (40%) but not in brain iron. The effect of the neuroleptic drug on iron stores and the involvement of iron in the neuroleptic-induced dopamine supersensitivity suggest that mobilization of iron from the periphery into the brain may play an important role in the mechanism of action of the neuroleptics.
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PMID:Prevention of neuroleptic-induced dopamine D2 receptor supersensitivity by chronic iron salt treatment. 168 31

The acute lethality of various cytotoxic drugs (doxorubicin, vinblastine and nitrogen mustard) and long-term survival in a syngenic mouse-tumour system were studied at normal body temperature and at 28 degrees C induced by chlorpromazine. Chlorpromazine-induced hypothermia itself neither caused acute toxicity nor influenced long-term survival. Doxorubicin (15 mg/kg) and nitrogen mustard (6 mg/kg) lethality was reduced at decreased temperature. The median survival time increased significantly from 35 days in normothermic to 52 days in hypothermic doxorubicin-treated mice. With nitrogen mustard, no increase in long-term survival was seen in the hypothermic group. The acute lethality of vinblastine was enhanced by hypothermia and the long-term tumour survival was unaffected. Hypothermia or possibly chlorpromazine considerably modulates drug toxicity and possibly anti-tumoural activity.
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PMID:Chlorpromazine-induced hypothermia in tumour-bearing mice, acute cytotoxic drug lethality and long-term survival. 226 Dec 11

To investigate the effects on the central nervous system of severe cold stress with and without chlorpromazine, guinea pigs were treated with chlorpromazine or 0.9% NaCl and exposed to -20 degrees C or +23 degrees C for 1 h. Hypothalamic noradrenaline (NA), dopamine (DA), 5-hydroxy-tryptamine (5-HT), 3-methoxy-4-hydroxyphenyl ethylene glycol (MHPG), homovanillinic acid (HVA) and 5-hydroxy-indoleacetic acid (5-HIAA) were determined by high-performance liquid chromatography. Serum, urinary and vitreous fluid catecholamines, muscle and liver glycogen, and blood glucose were also measured. Chlorpromazine caused distinct hypothermia at -20 degrees C and slight hypothermia at +23 degrees C. The rise in hypothalamic MHPG, 5-HIAA and MHPG/NA and in 5-HIAA/5-HT ratios in the cold indicate increased noradrenergic and serotonergic activity. The latter was inhibited by chlorpromazine and a drug-induced inhibition of noradrenergic neurons could not be ruled out. Chlorpromazine increased the turnover of DA at room temperature and the same tendency was seen in the cold. The hypothermic animals had low serum catecholamines, indicating diminished sympathetic activity. The chlorpromazine-treated cold-exposed animals did not react to the environmental stress by sympathetic activation, as urinary NA and adrenaline were not elevated, but DA was excreted by all the drug-treated animals. Vitreous fluid NA and DA were elevated as an indicator of cold stress, and no drug effect was seen in this fluid.
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PMID:Chlorpromazine-induced alterations in hypothalamic amine metabolism and stress responses in severe cold. 247 37

Guinea-pigs were treated with chlorpromazine or 0.9% NaCl and exposed to +4 degrees C or +23 degrees C for 2 h. Hypothalamic noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT), 3-methoxy-4-hydroxyphenylethylene-glycol (MHPG), homovanillinic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined by high-performance liquid chromatography. Serum and urinary catecholamines, muscle and liver glycogen and blood glucose were also measured. Chlorpromazine caused deep hypothermia at this moderately cold temperature and slight hypothermia at room temperature. Cold increased the activity of noradrenergic and serotonergic neurons, as indicated by the increase in hypothalamic MHPG and 5-HIAA and also the MHPG:NA and 5-HIAA:5-HT ratios. A tendency towards drug-induced inhibition of hypothalamic serotonergic neurons was seen, although this was not significant. A drug-induced inhibition of noradrenergic neurons could not be ruled out. Increased drug-induced turnover of DA was observed in the cold, and a tendency in the same direction was seen at room temperature. Excretion of DA into the urine was induced by chlorpromazine. The hypothermic guinea-pigs had low serum catecholamines, indicating diminished sympathetic activity, but high urinary catechols, a sign of cold stress.
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PMID:Effects of chlorpromazine on hypothalamic aminergic neurons and stress responses in moderate cold. 275 78


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