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 effect of delta 9-tetrahydrocannabinol (delta 9-THC) on body temperature of the mouse was studied. A dose-response relationship (5-100 mg/kg) for the hypothermic effect of delta 9-THC was seen. The investigation as to the mechanism underlying the hypothermic action of delta 9-THC was also investigated. The relatively specific dopamine antagonist haloperidol potentiated delta 9-THC-induced hypothermia as did the alpha-adrenoceptor antagonist phenoxybenzamine. However, depletion of serotonin with P-chlorophenylalanine reduced the hypothermic response to delta 9-THC as did pretreatment with the serotonin antagonist methysergide. Inhibition of re-uptake of serotonin with clomipramine potentiated the hypothermia following delta 9-THC. It is suggested that the hypothermic effect of delta 9-THC in the mouse is mediated to a large extent via serotonergic mechanisms.
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PMID:The mechanism of action of delta 9-tetrahydrocannabinol on body temperature in mice. 625 5

The administration of 0.3-40 mg/kg delta 9-tetrahydrocannabinol (THC) produced a dose-dependent hypothermia in rats. The maximal hypothermic effect was obtained with the dose of 2.5 mg/kg of THC. When the same doses of THC were repeated on days 2 and 3, tolerance to the hypothermic effect of THC was apparent. Doses of THC higher than 2.5 mg/kg induced a significant and dose-dependent tolerance after the first administration whereas with the lower doses, tolerance was only apparent after the second injection. The possible mechanism of these effects of THC is discussed.
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PMID:Correlation between the dose and development of acute tolerance to the hypothermic effect of THC. 626 Dec 69

Chlornaltrexamine (beta-CNA) a selective, long-acting irreversible opiate antagonist inhibited the analgesia, hypothermia, hypothermia tolerance and physical dependence produced by delta 9-tetrahydrocannabinol (THC) in rats. The results suggest that there are some common features between cannabis and opiates and some actions of THC may be mediated by opioid related mechanisms in the central nervous system.
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PMID:Antagonism by chlornaltrexamine of some effects of delta 9-tetrahydrocannabinol in rats. 626 44

Morphine and delta 9-tetrahydrocannabinol (THC) have been shown to have certain pharmacologic characteristics in common. Among these are antinociception, hypothermia, and the suppression of precipitated abstinence in morphine-dependent rats. In the present study the effects of morphine were compared with the effects of THC and two synthetic cannabinoids, nantradol and nabilone, in both nondependent and morphine-dependent chronic spinal dogs. Single doses of THC, nantradol, and nabilone depressed the flexor and skin twitch reflexes and had a calming effect after intravenous infusion. These effects are similar to those of morphine. Morphine, nantradol, and nabilone, but not THC, depressed rectal temperature. Unlike morphine, however, the cannabinoids produced mydriasis and an increased startle response, and these effects were not antagonized by naltrexone. THC, nantradol, and nabilone suppressed withdrawal abstinence in 40-hour and maximally abstinent morphine-dependent chronic spinal dogs. The results suggest that THC, nantradol, and nabilone share some properties with morphine since they increased the latency of the skin twitch reflex and suppressed withdrawal abstinence. It is doubtful, however, that these actions of the cannabinoids are mediated through opioid receptors since they were not antagonized by naltrexone.
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PMID:A comparison of THC, nantradol, nabilone, and morphine in the chronic spinal dog. 627 35

1 Whole brain and regional brain levels of prostaglandin E2 (PGE2)-like material have been determined following administration of delta 9-tetrahydrocannabinol (delta 9 -THC) in rats. 2 Intravenous administration of delta 9-THC 2 mg/kg, resulted in marked behavioural changes and hypothermia. The behavioural changes consisted mainly of catatonia (most apparent at 30 min after administration of delta 9-THC), followed by sedation (most evident at 60 min). Hypothermia was marked from 30 min after administration of delta 9-THC. 3 delta 9-THC did not after the whole brain levels of PGE2-like material 30, 60 or 120 min after administration. 4 delta 9-THC did not alter the levels of PGE2-like material in the medulla oblongata/pons, midbrain, cortex and cerebellum, 30 min after administration. However, there was a significant reduction of PGE2-like material in the hypothalamus, 30 min after delta 9-THC. 5 It is suggested that the delta 9-THC-induced decrease in hypothalamic PGE2-like material may contribute to the hypothermia observed following delta 9-THC administration.
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PMID:Alteration in the level of endogenous hypothalamic prostaglandins induced by delta 9-tetrahydrocannabinol in the rat. 628 71

The behavioral and pharmacological interactions between delta 9-tetrahydrocannabinol (delta 9-THC) and phencyclidine (PCP) were studied following coadministration of the drugs in smoke to mice. While delta 9-THC (25, 50 or 100 mg/cigarette) had little effect on spontaneous motor activity, all doses attenuated the hyperactivity elicited by PCP X HCl (25 and 50 mg/cigarette). delta 9-THC produced a dose-related hypothermia. PCP X HCl (50 mg/cigarette) had no effect on body temperature but enhanced hypothermia when combined with 25 mg of delta 9-THC. delta 9-THC (100 mg/cigarette) had no effect on the biodisposition of 3H-PCP and its pyrolytic product, 3H-phenylcyclohexene (3H-PC), when examined immediately after 3H-PCP X HCl (50 mg/ cigarette) exposure. At 30 min, brain, liver, lung and plasma contained higher concentrations of 3H-PC and fat and plasma contained lower concentrations of 3H-PCP in the mice exposed to both drugs compared to 3H-PCP X HCl alone. It appears, therefore, that delta 9-THC has the potential for altering the behavioral, pharmacological and pharmacokinetic sequelae of PCP abuse.
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PMID:Interactions between phencyclidine and delta 9-tetrahydrocannabinol in mice following smoke exposure. 629 42

delta 9-Tetrahydrocannabinol (delta 9-THC) was injected into the preoptic area of the anterior hypothalamus or into the third or fourth cerebral ventricle of the conscious mouse through a chronically implanted cannula and the effects on body temperature and oxygen consumption rate were measured. At an ambient temperature of 22 degrees C, injections of delta 9-THC into the fourth ventricle (5 and 10 microgram) produced dose-dependent falls in rectal temperature. Hypothermia was also observed after injections of the drug into the hypothalamus (5 and 10 microgram) or into the third ventricle (10 microgram). The hypothermia produced by delta 9-THC was associated with a fall in oxygen consumption rate. Falls in rectal temperature and in oxygen consumption rate were significantly greater after injection of delta 9-THC than after injection of the drug vehicle, Tween 80. The falls in rectal temperature and oxygen consumption rate produced by injection of delta 9-THC into the fourth ventricle were abolished by elevation of the ambient temperature from 22 to 32 degrees C. A pretreatment that consisted of subcutaneous injections of delta 9-THC (20 mg/kg) given once daily for three days produced tolerance to the hypothermic effect of the drug when injected on day 4 either into the fourth ventricle (10 microgram) or into a lateral tail vein (2.0 mg/kg). The results suggest that delta 9-THC acts centrally to alter thermoregulation in mice not only when it is injected directly into the hypothalamus or cerebral ventricles but also when it is given intravenously. After intraventricular or intravenous administration the drug may act at extrahypothalamic as well as at hypothalamic sites. The data also support the hypothesis that in mice, tolerance to the hypothermic effect of A9-THC is pharmacodynamic and does not depend on changes in metabolism or distribution of the drug.
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PMID:Changes in body temperature and oxygen consumption rate of conscious mice produced by intrahypothalamic and intracerebroventricular injections of delta 9-tetrahydrocannabinol. 631 10

9 alpha, 10 alpha-Epoxyhexahydrocannabinol (9 alpha, 10 alpha-EHHC) was found to be formed from delta 9-tetrahydrocannabinol (delta 9-THC) by liver microsomes of mice pretreated with phenobarbital. Further, pharmacological effects of 9 alpha, 10 alpha-EHHC in mice were compared with those of delta 9-THC using catalepsy, hypothermia, pentobarbital-induced sleep prolongation and anti-convulsant activity against pentylenetetrazol as indices. 9 alpha, 10 alpha-EHHC was approximately equipotent with delta 9-THC in the pharmacological indices except for catalepsy. The cataleptogenic effect of the epoxide was about 4 times as potent as the parent compound. From these results, it is suggested that 9 alpha, 10 alpha-EHHC can contribute to the pharmacological effects of delta 9-THC as an active metabolite.
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PMID:9 alpha, 10 alpha-epoxyhexahydrocannabinol formation from delta 9-tetrahydrocannabinol by liver microsomes of phenobarbital-treated mice and its pharmacological activities in mice. 631 13

This basic fraction (BF) of marihuana whole smoke condensate was subjected to pharmacological testing in males, Swiss-Webster mice. In a general pharmacological activity screen looking at behavioral, neurologic, and autonomic parameters, BF, at iv doses of 5, 10, and 20 mg/kg, caused impairment of visual placing, increase in tail pinch response, decrease in tail elevation, and induction of piloerection. These effects, although statistically significant, were slight and not consistently dose dependent. In a second study with doses ranging from 10 to 29 mg/kg, BF caused a decrease in spatial locomotion, rearing behavior, and urination incidence. In a third study, body temperatures of mice were measured periodically for 2 hr following administration of BF (1.2, 2.4, and 4.8 mg/kg) alone or in combination with 1.0 mg/kg delta-9-tetrahydrocannabinol (THC). BF did not alter body temperature, nor did it affect THC-induced hypothermia. These results, although suggesting that the basic fraction of marihuana whole smoke condensate has pharmacological activity in mice, offers little evidence for the presence of highly active compounds.
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PMID:Pharmacological activity of the basic fraction of marihuana whole smoke condensate alone and in combination with delta-9-tetrahydrocannabinol in mice. 632 14

delta 9-Tetrahydrocannabinol (THC), 11-hydroxy delta 9-tetrahydrocannabinol (11-OH-THC) and the synthetic dimethylheptyl analogue of THC (DMHP) were injected intracerebrally into proven chemosensitive sites in the hypothalamus of unanesthetized cats with implanted microinjection guide tubes. 100 micrograms of each compound was administered in a volume of 8 microliters. Chemosensitivity of all injection sites was established by microinjection of carbamylcholine to induce hyperthermia and tetrodotoxin to induce hypothermia. THC or its analogues produced no significant change in body temperature when injected intracerebrally. However, in the same animals, parenteral administration of THC, 11-OH-THC or DMHP (0.5 to 2.0 mg/kg) induced hypothermic responses ranging from -2.0 to -7.0 degrees C. Intravenous administration of THC was effective in blocking shivering induced by cooling the preoptic region in unanesthetized cats with implanted thermodes. In cats with mid-pontine transections, cooling of the spinal cord by perfusion with an epidural double wall cannula at temperatures of 30, 20, 10 and 0 degrees C produced graded shivering which was recorded electromyographically. Intravenous THC, (0.25-2.0 mg/kg) produced a dose-dependent attenuation of spinal cord induced shivering. These data plus results of prior studies suggest that the tetrahydrocannabinols produce their hypothermic effect at sites in the caudal brainstem. Suppression of shivering at the ponto medullary or spinal cord level may represent an important mechanism which contributes to the lowering of body temperature.
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PMID:Evidence for a caudal brainstem site of action for cannabinoid induced hypothermia. 722 5


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