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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pharmacological effects (catalepsy, hypothermia, pentobarbital-induced sleep prolongation, anticonvulsant and analgesic effects) of delta 8- and delta 9-tetrahydrocannabinols, and their 11-hydroxy-metabolites were evaluated and compared in mice. delta 9-Tetrahydrocannabinol and 11-hydroxy-delta 9-tetrahydrocannabinol exhibited somewhat greater effects than did delta 8-tetrahydrocannabinol and 11-hydroxy-delta 8-tetrahydrocannabinol, respectively, in all pharmacological indices tested. Greater effects of 11-hydroxy-metabolites than those of tetrahydrocannabinols were also demonstrated.
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PMID:Comparison of pharmacological effects of tetrahydrocannabinols and their 11-hydroxy-metabolites in mice. 217 83

Administration of delta 9-tetrahydrocannabinol (THC; 0.75-4.0 mg/kg IP) to rhesus monkeys produced a biphasic pattern of high-voltage slow waves (HVSW) and fast waves (HVFW) EEG, along with behavioral depression and alertness, respectively. The HVSW phase appeared 20 to 30 min after drug injection and was uniquely characterized by spike-bursts in frontal and temporal lobes and hypothalamus, theta-waves in parietal and occipital lobes, and generalized HVSW in subcortical regions. During the HVSW phase, bradycardia and hypothermia occurred, and animals exhibited depression or sedation. After the HVSW phase lasting for 3-4 hr, HVFW predominated in overall EEGs with marked decrease in neocortical spike-bursts. Bradycardia and hypothermia occurred simultaneously 20 to 30 min after drug injection and reached maximal levels (30-40 percent decrease in heart rate, 1.5-2.0 degrees C decrease in body temperature) 2 to 3 hr after injection. The dose- and time-response relationships for bradycardia and hypothermia paralleled the HVSW phase with behavioral depression. Animals were alert and calm during recovery from bradycardia and hypothermia. THC levels and disposition in blood correlated with bradycardia, hypothermia and EEGs and behavioral changes following THC administration.
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PMID:delta 9-Tetrahydrocannabinol: EEG changes, bradycardia and hypothermia in the rhesus monkey. 282 7

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

The present studies examine some of the pharmacological effects of delta-9 (11)-tetrahydrocannabinol (delta 9-11-THC), an analog of delta-9-tetrahydrocannabinol (delta 9-THC). In tests with mice, delta 9-11-THC was similar to but less potent than delta 9-THC in producing hypothermia, analgesia, lethality and in reducing spontaneous activity. In dogs delta 9-THC but not delta 9-11-THC produced classical cannabimimetic signs including static ataxia, hyperreflexia, prancing and tail-tuck. delta 9-11-THC did produce central nervous system depression in 9 of the 15 dogs tested but the effects were not dose-related and appeared earlier and dissipated faster than the depressive effects induced by delta 9-THC. delta 9-THC but not delta 9-11-THC produced signs of ptosis, sedation and ataxia in rhesus monkeys. delta 9-THC also suppressed operant responding completely in four of four monkeys tested whereas in one monkey delta 9-11-THC did not do so up to doses as high as 5.0 mg/kg and was 8 to 100 times less potent in doing so in the other monkeys. When monkeys were pretreated with delta 9-11-THC the doses of delta 9-THC required to produce ptosis, sedation, ataxia and operant suppression were increased. However, when mice and dogs were pretreated with delta 9-11-THC the effects of delta 9-THC were not attenuated and usually were enhanced. The pharmacological profile of delta 9-11-THC is unusual in that it seems to have cannabimimetic activity in mice, noncannabimimetic-like effects in dogs and is perhaps devoid of cannabimimetic effects in rhesus monkeys. In addition, pretreatment with delta 9-11-THC attenuates the cannabimimetic effects of delta 9-THC in rhesus monkeys but not in mice or dogs.
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PMID:Studies on the agonistic activity of delta 9-11-tetrahydrocannabinol in mice, dogs and rhesus monkeys and its interactions with delta 9-tetrahydrocannabinol. 303 18

Pretreatment with subhypothermic doses of chlorpromazine, given directly into the IIIrd cerebral ventricle via a chronically implanted cannula (50 micrograms) or subcutaneously (0.75 mg/kg), was found to enhance the hypothermic response to delta-9-tetrahydrocannabinol (THC: 5 20 mg/kg i.p.) in unrestrained adult male MF1 mice, kept at 22 degrees C. Subcutaneous pretreatment with a subhypothermic dose of phentolamine (30 mg/kg) had a similar effect, whereas pretreatment with desipramine (10 mg/kg s.c.), mepyramine (2.3 and 11.5 mg/kg s.c.), methysergide (2 mg/kg s.c.), pimozide (1 and 5 mg/kg s.c.) or lignocaine (50 mg/kg s.c.), had no effect. Intracerebroventricular pretreatment with phentolamine was also without effect and it is concluded that this drug interacts with THC at some site located outside the brain. Since, in mg/kg terms, chlorpromazine was more potent in enhancing THC-induced hypothermia when given subcutaneously than when injected into the IIIrd ventricle, it too may interact with THC at a peripheral site. Indeed, chlorpromazine and phentolamine may both increase the hypothermic response to THC by antagonizing alpha-adrenoceptors on cutaneous blood vessels, thereby decreasing the capacity of animals to minimise peripheral blood flow by vasoconstriction. Alternatively, since the distribution of chlorpromazine within the brain may well have been less efficient after intraventricular than after subcutaneous injection, the possibility remains that chlorpromazine interacted centrally with THC.
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PMID:Enhancement of the hypothermic response of mice to delta-9-tetrahydrocannabinol by subhypothermic doses of chlorpromazine and phentolamine. 303 14

1-N,N-bis-(Dichloroethyl)carbamate-delta 9-THC (THC carbamate), a nitrogen mustard analog of delta 9-THC, was recently synthesized as a potential anti-tumor agent. The decrease in spontaneous activity, induction of hypothermia, and the antinociceptive properties of THC carbamate and delta 9-THC were compared. THC carbamate and delta 9-THC were administered by a number of peripheral routes as well as intraventricularly (ivt). THC carbamate lacked cannabinoid activity following peripheral administration, with the exception of iv administration which produced very weak cannabimimetic effects. In contrast, THC carbamate was equipotent to delta 9-THC in reducing rectal temperature by 3 degrees C, and 5 times less active in decreasing spontaneous activity following ivt administration. The apparent lack of central effects following peripheral administration might limit the effectiveness of THC carbamate as an anti-emetic agent, but its use as a site-directed alkylator (a receptor probe) holds promise.
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PMID:Pharmacological profile of delta 9-THC carbamate. 304 25

The pharmacological potency of R- and S-3'-hydroxy-delta 9-tetrahydrocannabinol (THC) was compared to that of delta 9-THC as well as R/S-3'-OH-delta 9-THC. The S-isomer was found to be considerably more potent than the R-isomer in producing hypoactivity in mice, static-ataxia in dogs, and in generalization testing in rats trained to discriminate delta 9-THC from vehicle. S-3'-OH-delta 9-THC was more active than delta 9-THC in these tests which means that delta 9-THC may be either activated or inactivated in vivo depending upon which metabolite is formed. The difference in potency of these isomers suggests that the conformation of the side chain is critical for behavioral activity. The R and S isomers were found to be equally active in producing hypothermia in mice which is in contrast to the behavioral effects.
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PMID:Pharmacological potency of R- and S-3'-hydroxy-delta 9-tetrahydrocannabinol: additional structural requirement for cannabinoid activity. 608 79

The effects of clomipramine HCl (15 mg kg-1 i.p.) on behaviour, body temperature and brain amines were investigated in rats that had been chronically treated twice daily with increasing doses of delta 9-tetrahydrocannabinol (delta 9-THC, 2-6 mg kg-1 i.v.). delta 9-THC produced a biphasic change in behaviour, stimulation followed by depression, and a pronounced hypothermia. Tolerance developed rapidly to these effects of delta 9-THC. Chronic treatment with delta 9-THC reduced the levels of homovanillic acid, 5-hydroxytryptamine and noradrenaline. The level of dopamine was not altered with chronic treatment and tolerance appeared to develop to the increased levels of 5-hydroxyindoleacetic acid induced by delta 9-THC. Injection of clomipramine, 12-14 h after 2, 5 or 10 days of delta 9-THC treatment induced characteristic changes in the rats behaviour which consisted of writhes, backward kicking, wet shakes, jumps ataxia and front paw and whole body tremor. The severity of the behavioural changes appeared to be dependent on the period of delta 9-THC administration and they were not accompanied by a change in body temperature or consistent changes in brain amines or metabolites. The results indicate that physical dependence on delta 9-THC may occur since clomipramine is able to precipitate changes in behaviour, indicative on an abstinence syndrome, in rats chronically treated with delta 9-THC. It is suggested that tryptaminergic mechanisms are altered during chronic delta 9-THC treatment and that clomipramine induces the behavioural changes by interacting with an altered tryptaminergic system.
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PMID:Time-course of the effects of chronic delta 9-tetrahydrocannabinol on behaviour, body temperature, brain amines and withdrawal-like behaviour in the rat. 612 98

Thermosensitive anterior hypothalamic neurons (pre-optic region) were studied in urethane and chloralose anesthetized cats in an attempt to characterize the hypothermic action of delta 9-THC at the neuronal level. One hundred and seventy-eight single neurons were isolated and subjected to thermal challenge, 66 were found to reproducibly alter firing frequency at a significant level (thermosensitivity (T.S.) greater than 0.75). Twenty-one of these units met the criteria for primary thermodetectors, 34 were heat-sensitive interneurons, and 11 were cold-sensitive interneurons. Administration of delta 9-THC (1.0-2.0 mg/kg i.v.) decreased the spontaneous firing and increased the T.S. of the primary thermodetector units. delta 9-THC also increased the spontaneous firing frequency as well as the T.S. of heat-sensitive interneurons, while decreasing both the T.S. and spontaneous firing of cold-sensitive interneurons. The decreased spontaneous firing of primary thermodetectors could result from altered facilitory or inhibitory influences converging on these cells. The increased thermosensitivity is consistent with the hypothesis that the pre-optic region modulates cannabinoid-induced hypothermia.
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PMID:Effect of delta 9-tetrahydrocannabinol on hypothalamic thermosensitive units. 624 51

The effects of delta 9-tetrahydrocannabinol (THC) on body temperature, catecholamine synthesis and plasma corticosteroid levels were examined in the mouse at ambient temperatures of 31 degrees, 20 degrees and 10 degrees C in order to study the role of hypothermia in the THC's other actions. THC produced hypothermia at 10 degrees and 20 degrees C, but not at 31 degrees C. Dose related increases in dopamine and norepinephrine synthesis rates and plasma corticosterone levels were produced by THC at both 31 degrees and 20 degrees C. The effects of THC at 10 degrees C were biphasic. These data indicate that the effects of THC on brain catecholamines are not a result of drug induced hypothermia and may be a result of a direct action on neurons.
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PMID:Interaction of ambient temperature with the effects of delta 9-tetrahydrocannabinol on brain catecholamine synthesis and plasma corticosterone levels. 624 38


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