Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clonidine is able to increase the threshold for vocalisation during stimulation and the threshold for vocalisation after withdrawal of stimulus (vocalisation afterdischarge). These effects of clonidine were investigated after treatment of rats with drugs influencing central monoaminergic and cholinergic mechanisms. Chlorpromazine, atropine and p-chlorophenylalanine increased the activity of clonidine at both thresholds while phenoxybenzamine and reserpine pretreatment increased the activity at the thresholds for vocalisation only. Yohimbine decreased clonidine activity at both thresholds while 5-HTP and alpha-methyl-p-tyrosine decreased the effects at the threshold for vocalisation afterdischarge. Naloxone did not change the activity of clonidine at either pain response studied. It is concluded from the present findings that influence from several neuronal systems modulate the antinociceptive action of clonidine. The inhibition of the medullary nociceptive response after clonidine might be connected to a decreased activity of noradrenergic neurons. Endogenous noradrenaline seems to be of minor importance in mediating this effect. It is moreover shown that decreased cholinergic receptor activity enhances clonidine antinociceptive action on both medullary and diencephalic-rhinencephalic pain responses. The possible involvement of serotonin these functional responses after clonidine is also discussed.
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PMID:Clonidine antinociceptive activity: effects of drugs influencing central monoaminergic and cholinergic mechanisms in the rat. 13 92

The antihypertensive agent, clonidine, has a marked sedative effect. We studied whether clonidine also deepens halothane anaesthesia. Eight rabbits were anaesthetized with and without clonidine premedication in a cross-over study. Clonidine premedication (50 microgram/kg subcutaneously) was administered three times daily for 3 days. Tolerance to pain during halothane anaesthesia was tested by compressing the ear with a vessel clamp. Halothane concentrations were determined by gas chromatography. The rabbits premedicated with clonidine tolerated painful stimuli without reactions at lower halothane concentrations in arterial blood and inspired air than unpremedicated rabbits. MAC calculated from blood concentrations was 1.29% for unpremedicated and 1.09% for clonidine-premedicated rabbits. The results suggest that clonidine diminishes the anaesthetic requirement in halothane anaesthesia.
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PMID:The potentiation of halothane anaesthesia by clonidine. 42 9

11 coronary patients, 8 with mild hypertension, were treated with clonidine, at a dose of 75 micrograms b.i.d. per os for a week. The effect of the drug on coronary heart disease was assessed by means of a symptom-limited multistage exercise test on the cycloergometer. Clonidine was effective in reducing the exercise-induced increases in blood pressure (by 15.5 +/- 6.1%), the double product (by 34.8 +/- 20.8%) and the electrocardiographic ischemic changes. In 2/4 patients, effort related ventricular extrasystoles were reduced by greater than 50% after clonidine. The drug worsened the anginal pain in 3 and relieved the pain in 3 patients. However, it reduced the exercise-induced ST-T segment downsloping in 7 patients. The tolerance was good, since only 3/11 patients reported slight dry mouth, sedation and pyrosis. In view of the electrocardiographic effect, further studies with clonidine on myocardial ischemia should be performed.
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PMID:The therapeutic value of clonidine in patients with coronary heart disease. 49 82

Clonidine was found to possess dose-dependent analgesic and antiwithdrawal activity. In mice, clonidine prolonged the tail flick latency and inhibited phenylquinone-induced writhing. In rats, it inhibited tail withdrawal from hot water and a pain response to pressure application on an inflamed paw. The effective doses of clonidine were different in the different tests employed, but they were always smaller than those of morphine. Naloxone failed to antagonize the analgesic actions of clonidine but effectively antagonized those of morphine. Phenoxybenzamine also did not alter the inhibition of tail flick-induced by clonidine. Clonidine suppressed morphine withdrawal body shakes in a dose-dependent manner as does morphine. This action of clonidine was not reversed by naloxone. In usual laboratory tests, clonidine appears to be an effective analgesic which antagonizes signs of morphine withdrawal.
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PMID:A comparison of clonidine with morphine for antinociceptive and antiwithdrawal actions. 56 95

Opiate-adrenergic interactions were investigated by studying the effect of the selective alpha 2-adrenergic agonist, clonidine, on the analgesia produced by intravenous placebo and by the predominantly kappa-opiate agonist, pentazocine, in patients with dental postoperative pain. Clonidine did not affect the pain level when administered with intravenous placebo. When administered with pentazocine, clonidine caused a statistically significant increase in pentazocine analgesia. Comparison is made to other opiate-adrenergic interactions and possible mechanisms are discussed.
Pain 1992 Feb
PMID:Enhancement of pentazocine analgesia by clonidine. 135 Mar 40

The role of central nor-epinephrine (NE) in electroacupuncture (EA) analgesia is a controversial question., it is probably due to the complication of adrenergic receptors. The present results show: (1) Clonidine 30 micrograms/2ml/kg ip had no significant effect on the pain threshold, but decreased the analgesic effect of EA. Clonidine 1.5 and 3 micrograms were injected into the lateral cerebral ventricles. After 45 minutes, the analgesic effect of EA was lowered as compared with the saline controls respectively. (2) Yohimbine had no significant effect on the basal pain threshold, but (icv Yoh 50 micrograms) elevated the analgesic effect of EA. (3) 2-adrenoceptor agonist methoxamine decreased the analgesic effect of EA. (4) Another 2-adrenoceptor antagonist prazosin (icv 16 micrograms) enhanced the analgesic effect of EA. These results suggest that an activation of alpha 1- or alpha 2-adrenoceptors would decrease the analgesic effect of EA.
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PMID:[Effects of four adrenergic drugs on electroacupuncture analgesia]. 136 74

The intrathecal administration of prostaglandin F2 alpha to conscious mice resulted in spontaneous agitation and touch-evoked agitation (allodynia) in the animals. The maximum allodynia induced by prostaglandin F2 alpha was observed at 10-15 min after intrathecal injection, and the response did not disappear by 120 min. Prostaglandin F2 alpha produced allodynia over a wide range of dosage from 0.1 pg to 2.5 micrograms/mouse. Dose dependency of prostaglandin F2 alpha for allodynia showed a skewed bell-shaped pattern, and the maximal allodynic effect was observed at 1.0 microgram. This allodynia was dose-dependently relieved by alpha 1-adrenergic (methoxamine), alpha 2-adrenergic (clonidine), and A1-adenosine (RPIA) agonists. Clonidine was 1.5 orders of magnitude more potent than methoxamine in blocking prostaglandin F2 alpha-induced allodynia. The blockade by clonidine was dose-dependently reversed by the alpha 2-adrenergic antagonist yohimbine but not by the alpha 1-adrenergic antagonist prazosin. These results demonstrate that prostaglandin F2 alpha administered intrathecally induces allodynia in conscious mice and that the allodynia involves the alpha 2-adrenergic and A1-adenosine systems. Because this allodynia has a clear resemblance to the characteristics of chronic pain in patients with causalgia and reflex sympathetic dystrophy, prostaglandin F2 alpha may be involved in allodynia observed with these disorders.
Pain 1992 Aug
PMID:Allodynia evoked by intrathecal administration of prostaglandin F2 alpha to conscious mice. 140 21

Clonidine (Cl) added to local anaesthetics (LA) prolongs the duration of both anaesthesia and analgesia after peripheral nerve blocks. In this study, we investigated the dose-dependent effect of Cl added to mepivacaine (M) on clinical efficacy, onset, and regression time of brachial plexus block. METHODS. Ninety patients were randomly assigned to one of three groups. Every patient received 46 ml of a mixture containing 400 mg M (pH adjusted with NaHCO3 to 7.25) and either 0.9% NaCl (group A), 0.12 mg Cl (group B), or 0.24 mg Cl (group C). The axillary block was performed using the catheter technique. In a double-blind fashion, the onset of sensory and motor blockade was tested every 5 min for 30 min. Duration of anaesthesia, analgesia, and motor blockade (time between injection and return of sensation, onset of pain, or ability to move, respectively) was assessed using a questionnaire. M plasma levels were measured by HPLC in 10 patients from each group for up to 120 min. Blood pressure (BP), heart rate (HR), and respiratory rate (RR) were measured for up to 120 min. Sedation was assessed using a verbal rating scale. RESULTS. There was no difference in the onset of blockade. There was dose-dependent prolongation of the duration of anaesthesia, analgesia, and motor blockade with significant differences between groups C and A regarding all three parameters, between groups C and B regarding duration of anaesthesia, and between groups B and A regarding duration of analgesia. There was no significant difference in M plasma levels. Although there was only a slight but significant decrease in mean BP values in groups B+C and no difference in HR and RR, 2 patients (1 group B, 1 group C) had marked decreases in BP and HR (less than 70 mmHg systolic resp. less than 50/min) after 120 and 210 min. Sedation occurred in most patients receiving Cl. CONCLUSIONS. Addition of Cl to LA produces a dose-dependent prolongation of anaesthesia, analgesia, and motor blockade. Neither the onset time nor the number of patients with adequate surgical anaesthesia was influenced by Cl. Considering the M plasma levels, it is unlikely that the prolongation of the block is caused by local vasoconstriction, which is proposed to be the mechanism of action of epinephrine. The mean differences in haemodynamic parameters were not of clinical relevance, but the two dramatic drops in BP and HR, probably caused by Cl, were significant.
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PMID:[The effect of adding clonidine to mepivacaine. Axillary brachial plexus blockade]. 141 11

Previous research has shown that repeated daily pretreatment with the opiate receptor blocker naloxone retards the development of habituation to novelty-induced hypoalgesia. The present experiments were conducted in order to determine whether noradrenergic substrates mediates this effect. Animals in the NAL condition were administered 10 mg/kg naloxone prior to assessment of pain sensitivity on a 48.5 degrees C hot plate. Control animals (SAL condition) were administered saline prior to pain assessment, and naloxone 2-4 h later. Paw lick latencies declined over repeated tests in SAL animals, suggesting the habituation of novelty hypoalgesia. Naloxone pretreatment attenuated this decline. The longer paw lick latencies observed in NAL condition animals were reduced by administration of 2 microgram/kg clonidine, a specific noradrenergic alpha-2 receptor agonist, and enhanced in a dose dependent (0.5-4.0 mg/kg) fashion by the alpha-2 antagonist yohimbine. Clonidine and yohimbine either failed to alter pain reactivity in control animals, or produced less marked effects than those observed in naloxone-exposed animals. These results suggest that noradrenergic substrates mediate naloxone's effects on novelty hypoalgesia.
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PMID:Clonidine and yohimbine modulate the effects of naloxone on novelty-induced hypoalgesia. 160 2

Although clonidine analgesia appears to be mediated by the same central alpha 2-adrenoceptors that mediate its hypotensive effect, it is short-lasting when compared to the fall in blood pressure. This has been investigated by combined pharmacokinetic-pharmacodynamic analysis in 10 healthy volunteers who received (double-blind and crossover) clonidine 200 micrograms orally + placebo i.v. and clonidine orally + naloxone i.v. (2.8 mg/5 h). Analgesia was assessed by measuring the subjective (VAS) and objective (RIII) pain thresholds after transcutaneous electrical stimulations of the sural nerve; the mean arterial blood pressure (MAP), salivary flow (SF), and plasma clonidine concentrations were also monitored. A combined pharmacokinetic (first order absorption - 1 compartment) - pharmacodynamic (linear) model, including a hypothetical effect compartment with and without tolerance, were fitted to the data. Clonidine and clonidine + naloxone increased subjective and objective pain thresholds for 4 h. The concentration-effect plot for MAP showed distinct hysteresis. The t1/2s for effect compartment equilibration were 29 and 42 min for clonidine + naloxone and clonidine. The concentration-effect curves for RIII had the same shape as MAP but the starting hysteresis suddenly collapsed, suggesting acute tolerance. The best fit was obtained with a model where the linear relationship between concentration in the effect compartment and analgesia changed acutely after the third hour. The short-lived analgesia was probably related to an acute change in pain sensitivity induced by food, suggesting that it is not mediated solely by the alpha 2-adrenoceptors responsible for hypotension.
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PMID:Pharmacokinetic-pharmacodynamic modeling of the effects of clonidine on pain threshold, blood pressure, and salivary flow. 162 8


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