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)

Clonidine, an alpha 2 adrenergic agonist, has analgesic properties and recently has been used to suppress opiate withdrawal. These two properties theoretically make it a suitable analgesic substitute in patients tolerant to opioids. The objectives of this study were to see if intrathecal clonidine is analgesic and whether it can modify morphine withdrawal at the spinal level. Rats chronically implanted with catheters in the lumbar subarachnoid space were utilized. In analgesia experiments, intrathecal clonidine produced analgesia with the peak effect in the paw-lick test occurring at 200nM, and in the tail-flick test analgesia was apparent at 100 nM and peaked at 400 nM (in 10 microL Ringer's lactate). In dependency experiments, animals dependent on morphine (300 mg X kg-1) received intrathecal clonidine 25, 50, 200 nM in 10 microliter Ringer's lactate 72 h after morphine. Following this, a naloxone challenge, 3 mg X kg-1 was administered and withdrawal assessed. Clonidine-treated animals showed significant weight loss and decrease in temperature, and those treated with high doses showed marked hypothermia and hind-limb flaccidity. Intrathecal clonidine prevented the hyperalgesia associated with opiate withdrawal but did not affect the occurrence of the majority of behavioral signs (e.g., piloerection, irritability) associated with morphine withdrawal. Intrathecal clonidine prevented the naloxone-induced increase in blood pressure during withdrawal and in animals not treated with morphine-produced hypotension. Thus, intrathecal clonidine is analgesic, and part of the antiwithdrawal action of clonidine may be exerted at the spinal level.
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PMID:Intrathecal clonidine: analgesia and effect on opiate withdrawal in the rat. 403 43

Increasing doses of clonidine enhanced the retention of sulfobromophthalein (BSP) in plasma and liver, while reducing elimination of this dye into bile. The ED50 of clonidine for these effects was 0.05 to 0.2 mg/kg s.c. In clonidine-treated mice which were warmed to reverse drug-induced hypothermia, plasma and liver BSP levels were raised as compared to saline-treated mice. Clonidine also raised plasma and liver levels of the BSP analog, dibromosulfophthalein, which is not conjugated before biliary elimination. Hepatic glutathione levels, activity of glutathione-S-transferase and ratios of conjugated to unconjugated BSP were not affected by clonidine. In mice with cannulas in their common bile ducts to prevent duct spasm, clonidine reduced the amounts of BSP eliminated into bile. Thus, the alpha-2 adrenoceptor agonist, clonidine, raised plasma and liver levels of anionic dyes and reduced their levels in bile by mechanisms other than altered conjugation, hypothermia or bile duct spasm.
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PMID:Clonidine effects on sulfobromophthalein disposition in mice. 405 76

Systemic administration of angiotensin II (AII) to the rat has previously been shown to induce a dose-dependent, hypothermic response manifested by a fall in colonic temperature (CT), a decrease in heat production and an increase in tail skin temperature (TST). The factors mediating AII-induced hypothermia and their site of action were the subjects of the present investigation. To this end, intracerebroventricular administration of 1 microgram of AII induced a 0.4 degrees C reduction in CT and a 2.4 degrees C increase in TST. In contrast, SC administration of 200 micrograms angiotensin III/kg induced a slight increase in CT but had no affect on TST. Pretreatment with the AII-receptor antagonist, saralasin, at either 1 or 10 micrograms/kg, SC did not affect either the fall in CT or the increase in TST induced by administration of 200 micrograms AII/kg, SC. However, the administration of 100 micrograms saralasin/kg, SC attenuated both the fall in CT and the increase in TST induced by either 100 or 200 micrograms AII/kg. Since both the presynaptic alpha adrenoceptor agonist, clonidine, and the opioid antagonist, naloxone, modulate the pressor and dipsogenic responses to AII, their effects on AII-induced hypothermia were tested. Both clonidine (25 micrograms/kg, SC) and naloxone (1 mg/kg, IP) enhanced the fall in CT. Clonidine lengthened the duration of the increase in TST while naloxone had no effect. Pretreatment with the presynaptic adrenoceptor antagonist, yohimbine (300 micrograms/kg, SC), did not alter the hypothermic response to administration of AII. To determine whether vasodilation of the tail of the rat was mediated by AII-induced prostaglandin release, indomethacin (4 and 6 mg/kg) was administered.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Factors affecting angiotensin II-induced hypothermia in rats. 407 24

This review presents our new findings regarding the centrally-induced effects of histamine and clonidine. We have found for the first time that histamine administered intracerebroventricularly (icv) induces a dose-related increase in serum free fatty acids (FFA) in conscious rats. Both H1 and H2 receptors participate in this stimulation. Histamine interacts with central alpha 1 and beta-adrenoceptors and with cholinergic muscarinic receptors when inducing hyperlipemic response in non-stressed rats. Clonidine given icv induces also hyperlipemia which, as shown by us, is elicited by a central alpha 2-adrenergic mechanism. In hypothermia caused in rats by clonidine not only already known central alpha-adrenergic but also an H2-histaminergic mechanism participates to an equal extent. We have found for the first time that in conscious rats both under normal and stress conditions not only central histamine H1- but also H2-receptors mediate the stimulation of the pituitary-adrenocortical response measured indirectly through corticosterone secretion. In our study evidence has for the first time been obtained that in non-stressed rats brain histaminergic mechanism interacts with alpha 1, alpha 2- and beta-adrenoceptors and with cholinergic muscarinic receptors when stimulating the pituitary-adrenocortical response. By contrast, in stressed animals central histamine H1- and H2-receptors interact with alpha 1- and alpha 2- but not beta-adrenergic and cholinergic muscarinic receptors when increasing the corticosterone response. We have also demonstrated that in contrast to a known inhibitory action on adrenocortical secretion in anesthetized dogs, clonidine given icv increases the corticosterone response in both non-stressed and stressed rats by stimulating alpha-adrenoceptors. In stressed animals this effect of clonidine is also mediated, to an equal extent, by H2-receptor mechanism. Our data strongly suggest that in some central effects clonidine affects both alpha 2 and H2 receptor mechanism. This challenges the view that clonidine is a selective alpha-adrenergic agonist.
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PMID:Central metabolic and pituitary-adrenocortical stimulatory action of histamine and clonidine. 608 56

The effects of clonidine hydrochloride, an agent effective in suppressing other types of flushing reactions, were investigated in patients with erythematotelangiectatic rosacea. Clonidine hydrochloride, 0.05 mg, was given orally twice daily for two weeks. Mean arterial BP was not altered during clonidine treatment. Flushing reactions provoked with water at 60 degrees C, red wine, and chocolate were not suppressed during clonidine treatment. Clonidine did lead to malar hypothermia. It may be that any treatment benefit obtained from the reduction in vascular reactivity by clonidine in rosacea is offset by the malar hypothermia.
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PMID:Effect of subdepressor clonidine on flushing reactions in rosacea. Change in malar thermal circulation index during provoked flushing reactions. 621 89

Clonidine and several other structurally related imidazolidines were administered intraperitoneally to mice and their capacity to cause hypothermia was used as an indication of their ability to enter the central nervous system. The substances were: clonidine (2-[w,6 dichlorophenylimino] imidazolidine) and its 2, 6-disubstituted derivates: St 91 (2,6-diethyl), St 93 (2-chloro, 6-methyl), St 95 (2,6-dimethyl) and St 1697 (2-ethyl, 6-methyl). All caused dose-dependent reductions in body temperature. Clonidine was most potent and was effective over the range 62.5-500 millimicron/kg i.p. clonidine lowered body temperature by 2.9 0.15oC. Relative potencies (R) were: clonidine (R 1), St 91 (0.41), St 1697 (0.29), St 93 (0.21) and St 95 (0.06). Hypothermia was inhibited by piperoxan injected intracisternally (10 millimicron/kg) but not intraperitoneally (10 and 50 millimicron/kg). Following intracisternal administration, the imidazolidine dose response curves were shifted in a parallel fashion to the left relative to the intraperitoneal administration. It is suggested that these compounds can all cross the blood-brain barrier in mice and interact with central alpha-adrenoceptors to cause hypothermia. These findings are at variance with the abilities of some of these substances to cause sedation and hypotension mediated by interaction with central alpha-adrenoceptors.
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PMID:The hypothermic effect of clonidine and other imidazolidines in relation to their ability to enter the central nervous system in mice. 626 29

Clonidine and xylazine injected intraperitoneally both produced a dose-dependent hypothermia in unanaesthetized, freely moving rats. The alpha 2-antagonist yohimbine produced an antagonism of the xylazine-induced hypothermia but a potentiation of the clonidine-induced hypothermia. The opioid antagonist naloxone had little effect on the xylazine hypothermia, but potentiated the clonidine hypothermia. It is concluded that whilst the two alpha 2-agonists produce a similar hypothermic effect in the rat, they are acting by different mechanisms.
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PMID:Effects of clonidine and xylazine on body temperature in the rat. 670 81

Mice were pretreated once daily with L-DOPA (200 mg/kg) plus benserazide (B) (50 mg/kg) for ten days and challenged with various doses of L-DOPA + B on the first, fourth or sixteenth days of withdrawal. L-DOPA + B-pretreated mice were more sensitive the locomotor stimulant effect of L-DOPA + B challenge one and four days, but not sixteen days after withdrawal. The enhanced response was most marked on the first day of withdrawal. Other mice, pretreated once daily with B (50 mg/kg), responded one day after the tenth dose with a slightly enhanced response to L-DOPA + B challenge compared to the response to vehicle-pretreated animals. Moreover, vehicle-pretreated mice challenged with B alone, were significantly less active than those challenged with vehicle. On the first day of withdrawal, the L-DOPA + B-pretreated animals were supersensitive to locomotor stimulant effects of apomorphine but subsensitive to dexamphetamine (Bailey et al., 1979). On the fourth day of withdrawal, there were no differences in the responses of the L-DOPA + B-pretreated mice compared to the vehicle-pretreated mice, to apomorphine or apomorphine plus clonidine, but L-DOPA + B-pretreated mice were still subsensitive to the locomotor stimulant effects of dexamphetamine. Clonidine produced a dose-dependent, but similar, degree of hypothermia in both pretreatment groups. On the first and fourth days of withdrawal L-DOPA + B-pretreated mice exhibited higher brain levels of dopamine (DA) and DOPA than vehicle-pretreated mice in response to an acute dose of L-DOPA + B. The biochemical results suggest that the enhanced locomotor response to L-DOPA + B in L-DOPA + B-pretreated mice is probably dependent on changes in the amount of L-DOPA (and DA) available in the brain. Moreover, it is not ruled out that some of the effects of L-DOPA + B pretreatment were due to the B alone. Some of the enhanced response to L-DOPA + B on the first day of withdrawal may have been dependent on the same mechanism as that underlying the apparent supersensitivity to apomorphine. The subsensitive response to dexamphetamine would appear to be independent of changes in post-synaptic DA and alpha-adrenergic receptor sensitivity.
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PMID:Chronic L-DOPA treatment of mice: a behavioural and biochemical study. 678 71

Clonidine hydrochloride poisoning in children has become more frequent with increasing availability of this drug. We report four cases of accidental clonidine poisoning that demonstrate the various signs and symptoms of clonidine poisoning. The most frequent and significant toxic effects are depression of consciousness, bradycardia, hypotension, and respiratory depression. Ventilatory support must be available if apnea occurs. Bradycardia can be treated with atropine sulfate, epinephrine chloride, dopamine hydrochloride, or tolazoline hydrochloride. Hypotension is treated with intravenous fluids and dopamine, reserving tolazoline for refractory cases. Hypothermia is common but is of minor clinical significance. Paradoxical hypertension should be treated with tolazoline. Clonidine may not be detected in body fluids by routine toxicology-screening procedures, so poisoning should be suspected on clinical grounds.
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PMID:Clonidine poisoning. A complex problem. 684 4

Changes in core body temperature and the behavioral activation produced by clonidine were measured in 10-day-old rats at 3 different ambient temperatures (25, 30 and 36 degrees C). Behavioral activation after clonidine is comprised of head raising and rotational movements of the limbs which result in locomotion in open areas and wall climbing if the animal is confronted by a vertical surface. Clonidine enhanced locomotion and wall climbing at all environmental temperatures, but a drug-induced hypothermia was found only in the 25 and 30 degrees C testing conditions. This suggests that the clonidine-induced motor changes are not secondary to a fall in body temperature. In a second experiment the open field responses to clonidine at 25 degrees C were observed in 10-day-old rats pretreated with phentolamine (2 and 15 mg/kg), phenoxybenzamine (2 and 15 mg/kg) or naloxone (0.2 and 2 mg/kg). Phentolamine pretreatment at 15 mg/kg reduced locomotion, wall climbing and attenuated the reduction in core temperature. Phenoxybenzamine at 15 mg/kg only affected the clonidine-induced change in temperature. Thus, it is likely that these behavioral and temperature changes are adrenergically mediated and that the clonidine-induced locomotion and temperature effects may be due to different alpha-adrenergic receptors.
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PMID:Behavioral and temperature changes induced by clonidine in the developing rat. 732 39


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