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)

Chlorpromazine, given either subcutaneously (0.375 mg/kg) or unilaterally into the preoptic/anterior hypothalamic area through a chronically implanted cannula (20 micrograms), was found to enhance the hypothermic response to delta-9-tetrahydrocannabinol (THC; 5 mg/kg i.p.) in unrestrained adult male MF1 mice, kept at 22 degrees C. In mg/kg terms, chlorpromazine was no more potent when injected into the preoptic/anterior hypothalamic area than when given subcutaneously. Phentolamine (54 micrograms) had no significant effect on hypothermia induced by THC when injected into the hypothalamus although it did enhance this response when given subcutaneously (15 mg/kg). Hypothermia induced by THC was also enhanced by flupentixol (0.375 mg/kg s.c.), piflutixol (23.4 micrograms/kg s.c.), pentolinium (5 mg/kg s.c.), prazosin (0.1875 mg/kg s.c.) and indoramin (6 mg/kg s.c.) but not by SCH 23390 (6 mg/kg s.c.) or sulpiride (40 mg/kg s.c.). When taken together with the results from a previous study, these data support the hypothesis that chlorpromazine enhances hypothermia induced in mice by THC by antagonizing alpha-adrenoceptors so as to decrease the capacity of the animals to minimise peripheral blood flow by vasoconstriction. The present data also support the hypothesis that flupentixol and piflutixol interacted with THC not by antagonizing dopamine at D1 or D2 receptors but rather by blocking alpha-adrenoceptors.
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PMID:The hypothermic response of mice to delta-9-tetrahydrocannabinol is enhanced by chlorpromazine, thioxanthenes, alpha-adrenoceptor antagonists and pentolinium but not by SCH 23390 or sulpiride. 289 30

Chlorpromazine (CPZ) can decrease the toxicity of doxorubicin (DOX). We wanted to determine whether this CPZ pretreatment could affect the response of tumours to therapeutic doses of DOX. Six groups of eight female CDF1 mice received 1 million leukaemia P388D1 cells i.p. For 5 days, they received DOX i.p. (total dose 0, 6 or 12 mg/kg), preceded by saline or 5 mg/kg CPZ s.c. CPZ in the absence of DOX had no effect on survival [median survival time (MST) of 19 days vs. 20]. In mice receiving DOX only, MST was greater than 60 days. Mice receiving DOX + CPZ were similar to DOX till day 25, but subsequently died earlier (MST of 27 and 34 days, for DOX 6 and 12 mg/kg). At death or day 60, 31% (5/16) of DOX mice and 88% (14/16) of DOX + CPZ had macroscopic tumours (P less than 0.005, both DOX dose groups combined). However, only 19% (3/16) of DOX and 6% (1/16) of DOX + CPZ had tumours in the abdominal cavity, the others being in the abdominal wall close to the site of injection. The results suggests that while CPZ did not affect the killing of cancer cells in the abdominal cavity, it did block the effect of DOX on cells in the abdominal wall and skin. This block may be caused by decreased local delivery of DOX, due to the hypothermia produced by CPZ.
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PMID:Ambiguous effect of chlorpromazine on doxorubicin activity against P388D1 tumours in mice. 335 4

A simplified technique of the liver transplantation under hypothermia has been studied in dog. An immersion hypothermia was used in both the donor and the recipient. The temperature of the graft at excision was lowered to 20 degrees C with supplemental use of topical cooling. The temperature of the recipient was lowered at 27 degrees C when the transplantation was attempted. Chlorpromazine and dopamine were employed beneficially in hypothermia. No perfusion or irrigation of the graft was performed. The use of heparin was avoided. Anastomoses were carried out in turn of the proximal vena cava, portal vein, distal vena cava and the hepatic artery with a stem shaped aorta. Reperfusion was established after the completion of anastomosis between the proximal vena cava and portal vein. The anhepatic phase of the recipient was uneventfully lasted without heparinization. All dogs, 5 out of 11 without early surgical troubles survived more than 5 days. Immunosuppressive therapy was not employed except one which died of pneumonia on the 19th postoperative day. Histologically, these dogs were free from ischemic injury and/or thrombotic lesion throughout transplantation procedure.
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PMID:[Orthotopic allotransplantation of the canine liver; a simplified technic with hypothermia]. 352 Feb 86

Chlorpromazine increases the sensitivity of cells to doxorubicin; in vivo it also produces hypothermia, which has the contrary effect. To determine the net effect of these factors, we tested the toxicity of doxorubicin in mice which had developed chlorpromazine-induced hypothermia. Groups of 10 female Swiss albino mice received chlorpromazine (5 mg/kg sc). One hour later, when rectal temperature was 30 degrees C, doxorubicin. HCl (20 mg/kg ip) was injected. Median survival time was 10 +/- 2 days for controls and 48 +/- 5 days for chlorpromazine treated mice (4 experiments each). A high chlorpromazine dose (100 mg/kg) did not protect. Chlorpromazine (5 mg/kg) also reversed the slowing of weight gain by 5 mg/kg doxorubicin. If the drop in rectal temperature was prevented by keeping the mice at 32-35 degrees C, the protection by chlorpromazine was abolished. The results show that chlorpromazine protects against the toxicity of ip doxorubicin; the hypothermia produced by chlorpromazine seems to be essential for the protection.
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PMID:Protection against doxorubicin toxicity in mice by chlorpromazine hypothermia. 377 2

The effect of short-term administration of chlorpromazine and phenobarbital on cytoplasmic alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) was studied in distinct brain regions of the male rat. The effect of exposure to cold environment on the same enzymes was also evaluated. Chlorpromazine treatment resulted in inhibition of ADH and ALDH in the striatum and in the cerebellum, respectively. This inhibition was determined only when the animals were sacrificed 30 min but not 18 hr post terminal drug treatment. The pons-medulla content of ALDH was reduced by chlorpromazine treatment from controls 18 hr of terminal treatment. Hypothermic animals showed an inhibition of ADH in the diencephalon from corresponding controls. The phenobarbital treatment was devoid of action on hepatic ADH and ALDH. Concomitantly, an induction of both ADH and ALDH by pentobarbital was observed in the cerebellum and in the diencephalon, respectively. The effect of the drugs studied may contribute to their adverse interaction with ethanol on the central nervous system.
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PMID:Effect of centrally acting drugs on ethanol detoxification enzymes in distinct rat brain regions. 388 86

1. Chlorpromazine 15 mg/kg, given daily to cats for 2 weeks, produced a rise in homovanillic acid (HVA) content of the caudate nucleus, whereas the same dose of thioridazine lacked this effect. Of these two drugs, only chlorpromazine causes a high incidence of drug-induced Parkinsonism in man.2. In the mouse, chlorpromazine, thioridazine and haloperidol increased striatal concentrations of HVA and accelerated the disappearance of dopamine (DA) after inhibition of catecholamine synthesis with alpha-methyltyrosine. Low doses of the three compounds increased, whereas high doses reduced, the concentration of DA in the striatum. In their effects on the DA metabolism of the mouse, chlorpromazine and thioridazine had the same potency, but haloperidol was between 10 and 100 times more active than the other two drugs. In producing hypothermia and sedation, the three compounds were equiactive.3. Oxypertine, another drug apt to produce Parkinsonism in man, caused a severe reduction in striatal DA and hypothalamic noradrenaline (NA). Though the clinical signs produced in the mouse were indistinguishable from those seen after the same dose of chlorpromazine, the biochemical changes in the brain were thus quite different.4. Though all the drugs used caused temporary motor disabilities in animals, these bore no resemblance to human Parkinsonism, even when treatment was continued for 7 weeks or more as it was in cats and monkeys. The latter were treated with chlorpromazine 7.5 mg/kg daily, a dose chosen to avoid loss of weight and which may have been too small to produce toxic side-effects. It caused no changes in striatal DA turnover.5. Even at the high dose of 50 mg/kg, phenoxybenzamine did not increase DA turnover in mouse brain, but it sedated the mice as did the tranquillizers.6. Atropine sulphate, 25 mg/kg, reduced the HVA content of mouse striatum and partially antagonized the rise in HVA produced by phenothiazines. The effect was surmountable. Possible modes of action of atropine are discussed.7. At present we know of two types of biochemical changes which may occur in the brain of animals after treatment with drugs apt to cause Parkinsonism in man: a loss of cerebral catecholamines, as seen after reserpine or oxypertine, or an increase in turnover of DA as after phenothiazines and butyrophenones.
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PMID:Effect of drugs used in psychoses on cerebral dopamine metabolism. 498 1

The effects of beta-endorphin, MIF-I, and alpha-MSH on d-amphetamine- a CPZ-induced hypothermias in rats kept at 4 degrees C were tested in three experimental groups: (a) intact; (b) rats with lesions of the olfactory tubercle; and (c) rats in which the link between the DA mesolimbic pathway and the striatum was disconnected. All drugs tested alone (except MIF-I) caused significant hypothermia. Pretreatment with CPZ, MIF-I, and alpha-MSH potentiated d-amphetamine-induced hypothermia in intact rats. Pretreatment with alpha-MSH potentiated CPZ-induced hypothermia. beta-Endorphin partially blocked d-amphetamine-induced hypothermia, but did not interact with CPZ, MIF-I, or alpha-MSH. All potentiations were either reduced or disappeared in the incisioned rats. CPZ and alpha-MSH caused hypothermia in olfactory tubercle-lesioned rats. The results indicate that: (a) the DA mesolimbic pathway is involved in the hypothermic response of all drugs tested; (b) an intact feedback loop is required for the potentiation of the hypothermic response of CPZ on d-amphetamine, MIF-I on d-amphetamine, and alpha-MSH on d-amphetamine and CPZ; (c) beta-endorphin acts as a partial blocker of d-amphetamine; MIF-I is a weak potentiator of d-amphetamine, alpha-MSH acts as a negative modulator of the DA system, most probably in the striatum.
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PMID:Modification of d-amphetamine- or chlorpromazine-induced hypothermia by beta-endorphin, MIF-I, and alpha-MSH: mediation by the dopaminergic system. 612 51

1. Degeneration of nerve terminals of the submaxillary gland of the rat proceeds at a faster rate after crushing adrenergic nerves close to the gland than after ganglionectomy. 2. Bretylium, pargyline, nialamide and clorgyline delayed degeneration to the same extent after either type of denervation. 3. Chlorpromazine and pentobarbitone also delayed adrenergic degeneration, effect related to the hypothermia induced by these drugs. 4. Colchicine applied on the nerve trunk innervating the right gland delayed not only degeneration of the ipsilateral nerve terminals but the contralateral gland as well. 5. From the data obtained it seems probable that the drugs tested delay adrenergic nerve degeneration at the levels of nerve terminals. This effect is not related to lysosomal stabilization.
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PMID:Delay by drugs of adrenergic nerve degeneration after proximal or distal sympathectomy of the submaxillary gland. 709 98

The antileukemic combined effect of reserpine with 1-gamma-chloropropyl-2-chloromethylpiperidine hydrobromide (CAP-2) and other antitumor agents was studied on mouse leukemia L1210 in comparison with the effects of other Rauwolfia alkaloids and sympatholytic drugs. When reserpine was administered by a single ip injection (2.5 mg/kg) on day 1, the effect of subsequent administration of CAP-2, mitomycin-C, or vinblastine was synergistically enhanced. In this combination with reserpine, the acute lethality of CAP-2 on the host animals was apparently decreased. Among other sympatholytic drugs, rescinnamine, a central nervous system depressant, slightly potentiated the antitumor effect of CAP-2. On the other hand, when reserpine-induced hypothermia was prevented by maintenance of the ambient temperature at 30 degrees, the synergistic combined effect of reserpine was diminished. Chlorpromazine-induced hypothermia did not influence the antitumor effect of CAP-2. It may be concluded that the antileukemic synergism depends partially on the interaction between reserpine and CAP-2 or other antitumor agents in relation to body temperature and/or action on the central nervous system in leukemic mice.
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PMID:Comination effect of reserpine with antitumor agents in L1210. 741 86

Ca2+ accumulates in the nucleus and DNA undergoes enzymatic cleavage into internucleosome-length fragments before acetaminophen and dimethylnitrosamine produce hepatic necrosis in vivo and toxic cell death in vitro. However, Ca(2+)-endonuclease fragmentation of DNA is characteristic of apoptosis, a type of cell death considered biochemically and functionally distinct from toxic cell death. The present studies investigate DNA fragmentation as a critical event in toxic cell death by testing whether the Ca(2+)-calmodulin antagonist chlorpromazine and the Ca2+ channel blocker verapamil prevent acetaminophen-induced hepatic necrosis by inhibiting Ca2+ deregulation and DNA damage. Acetaminophen overdose in mice produced accumulation of Ca2+ in the nucleus (358% of control) and fragmentation of DNA (250% of control) by 6 h, with peak release of ALT occurring at 12-24 h (38,000 U/l). Pretreatment with chlorpromazine prevented increases in nuclear Ca2+ and DNA fragmentation and nearly abolished biochemical evidence of toxic cell death. Verapamil pretreatment also decreased Ca2+ accumulation and DNA damage while attenuating liver injury. The Ca2+ antagonists did not protect against toxic cell death through hypothermia because neither produced the delay in toxicity that is customarily associated with hypothermia. Nor did chlorpromazine or verapamil protect through inhibiting acetaminophen bioactivation. Chlorpromazine failed to diminish glutathione depletion in whole liver and isolated nuclei. Verapamil (250 microM) also failed to alter glutathione depletion in whole liver and had no effect on acetaminophen-glutathione adduct formation by mouse liver microsomes and by cultured mouse hepatocytes. Collectively, these results support the hypothesis that Ca(2+)-induced DNA fragmentation plays a significant role in cell necrosis produced by acetaminophen and may contribute to toxic cell death caused by other alkylating hepatotoxins.
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PMID:Ca2+ antagonists inhibit DNA fragmentation and toxic cell death induced by acetaminophen. 846 87


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