• Biomolecules & Therapeutics
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• v.4 no.2
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• pp.205-207
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• 1996

Clonidine, an antihypertensive drug, stimulates postsynaptic alpha-2 adrenergic receptors in the central nervous system and lowers arterial pressure through the effects on both cardiac output and peripheral resistance. However, many patients experience that sedation and xerostomia occur upon oral administration of clonidine. These side effects are due to high plasma peak concentration and can be avoided when clonidine is given transdermally. In this study, we tested the antihypertensive effects of trandermal administration of clonidine patch on spontaneously hypertensive rat (SHR) which is a model animal for human essential hypertension. Forty eight SHR (male) were divided into six groups according to the dose levels, respectively. After transdermal administration of clonidine patch of each dose, systolic blood pressure and heart rate were measured. Clonidine patch produced maximal antihypertensive and bradycardiac effects 48 hrs after administration and antihypertensive effects showed dose-dependency. We suggest that antihypertensive effects of clonidine patch are similar to those of orally given clonidine and clonidine patch can be used instead of clonidine tablet.

• Korean Journal of Pharmacognosy
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• v.21 no.1
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• pp.103-109
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• 1990

The antagonism against clonidine-induced analgesia by ginseng saponin (GS) and the inhibitory effect of GS on the development of clonidine-induced tolerance were evaluated in mice. GS, when administered systemically, intracerebrally and intrathecally, antagonized significantly the analgesic effect of clonidine. GS, when injected intraperitoneally not only inhibited the development of clonidine-induced analgesic tolerance, but also enhanced the analgesic effect of clonidine on the 2nd and 5th day. Naloxone did not antagonize the analgesic effect of clonidine and had no influence on the deveolpment of tolerance of both acute and delayed types. These results indicate that the antagonism against clonidine-induced analgesia and the inhibition of the deveolpment of clonidine-induced tolerance by GS are not mediated by the opioid mechanism.

• Journal of Yeungnam Medical Science
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• v.6 no.2
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• pp.57-62
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• 1989

Clonidine, ${\alpha}2$-adrenergic agonist, applied spinally or epidurally has been shown to be effective in blocking noxious stimuli in human applications. The purpose of this study is to evaluate the analgesic effect of epidurally administered clonidine. In 40 patients undergoing hemorrhoidectomy or anal fistulectomy, 1.33% lidocaine 15ml (Group I) or 1.33% lidocaine mixed with $75{\mu}g$ clonidine(Group II) administered epidurally through sacral hiatus. Intraoperative changes of vital signs and duration of postoperative analgesic effects were observed. The results were as follows : 1) In the group I, average analgesic duration was 2.42 hours. 2) In the group II, average analgesic duration was 7.32 hours. 3) After epidural clonidine injection, the decrease in heart rate and blood pressure was not significant without sedation. 4) Postoperatively, any complaints related clonidine were not reported. In conclusion, postoperative pain control with epidural clonidine was effective.

• Biomolecules & Therapeutics
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• v.1 no.2
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• pp.151-159
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• 1993

Effect of yohimbine, a specific antagonist for presynaptic adrenoceptor, on the renal action of clonidine, a specific presynaptic adrenoceptor agonist, was investigated in dog. Clonidine, when given intravenously, produced diuretic action accompanied with augmentation of osmolar and free water clearance (Cosm and 4C_{H_2O}$), and elicited the increase of amounts of sodium and potassium excreted in urine ($E_{Na}\; and\; E_k$). These actions of clonidine were inhibited by yohimbine either injected intravenously or infused into a renal artery. Clonidine, when infused into a renal artery, produced antidiuretic action accompanied with decreased of glomerular filtration rate (GFR) and renal plasma flow (RPF), and exhibited the reduced amounts of sodium and potassium in urine. These actions of clonidine injected into a renal artery were blocked by yohimbine administered either into vein or into a renal artery. Above results suggest that yohimbine block the renal action of clonidine only in central system, do not in kidney.

• Biomolecules & Therapeutics
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• v.4 no.2
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• pp.202-204
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• 1996

Clonidine, an antihypertensive drug, stimulates postsynaptic $\alpha_2$adrenergic receptors in the CNS and lowers arterial pressure by erects on both cardiac output and peripheral resistance. However, many patients experience that sedation and xerostomia occured upon oral administration of clonidine. These side effects are due to high plasma peak concentration and can be avoided when clonidine is given transdermally. In this study, we performed the skin irritation test for transdermal administration of clonidine patch on New Zealand white rabbits. Twelve New Zealand white rabbits were divided into two groups according to the dose levels, respectively. After transdermal administration of clonidine patch with two doses, clinical manifestations, body weight loss and postmortem findings were observed. We could not find any significant evidence of skin irritation by transdermal administration of clonidine patch.

• The Korean Journal of Pain
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• v.7 no.2
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• pp.205-210
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• 1994

The effects of either clonidine or epinephrine into local anesthetics administered into brachial plexus sheath were evaluated in 42 patients who underwent surgery of the upper limb. All patient received 0.5 ml/kg of 2:1 mixture of bupivacaine and lidocaine injected into the brachial plexus sheath, using the subclavian perivascular technique. The patients were randomly allocated into two groups; Group I(n=25) received $150{\mu}g$ of clonidine hydrochloride, and Group II(n=27) received $200{\mu}g$ of epinephrine. The duration of analgesia and the degree of sedation reflecting the systemic effect of clonidine were assessed. The block produced by the addition of clonidine was longer($100.3{\pm}469.8$ vs $648.8{\pm}192.1$ min) and superior to that by epinephrine(p < 0.05). The highest degree of sedation was achieved about 20 minutes after block, which roughly equals the time required for intramuscular clonidine to show the similar effect. The author concludes that the injection of clonidine mixed to local anesthetics into the brachial plexus sheath prolongs analgesia than that of epinephrine, but this prolongation may be due to the systemic effect of clonidine.

• YAKHAK HOEJI
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• v.27 no.4
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• pp.271-282
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• 1983

This study is an attempt to study the influence of clonidine, which has a central sympatholytic action, on the renal function in dogs and to elucidate its mechanism of action. Clonidine ($15\mu$g/kg) injected into a cephalic vein of the dog produced a marked increase in urine flow and in amounts of $Na^{+}$ and $K^{+}$ excreted in urine, and clearances of free water and osmolar substance, the reabsorption rates of $Na^{+}$ and $K^{+}$ in renal tubules were significantly decreased. Clonidine ($50.0]mu$g/kg) administered intravenouly elicited a transient reduction in urine flow, along with inhibition of all renal functions. Intravenous clonidine-induced diuretic effect was completely blocked by pretreatment with reserpine, and was lessened by water diuresis. Clonidine ($3.0\mu$g/kg) injected tnto a carotid artery revealed a transient diuresis with a increase in clearance of free water. Clonidine injected into a renal artery showed a significant antidiuretic effect and all functions of an experimental kidney were reduced. Antidiuretic action induced by clonidine given into a renal artery markedly suppressed by pretreatment with reserpine. The above results suggest that clonidine has dual mechanisms: 1) diuretic effect due to the central sympatholytic action and inhibition of release of antidiuretic hormone, and 2) antidiutetic effect indued by indirect symptheic stimulation in the periphery.

• The Korean Journal of Pharmacology
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• v.14 no.1_2
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• pp.13-23
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• 1978

1) It was attempted to clarify the sites of action of central (either intraventricular or intracisternal) norepinephrine(NE) and clonidine to cause cardiac slowing and hypotension in urethane-anesthetized rabbits. 2) NE produced cardiac slowing but indistinct effect on blood pressure. Clonidine produced cardiac slowing and hypotension. 3) Intraventricular and intracisternal administration of NE, clonidine, phenylephrine and isoproterenol did not make difference in their effects, except that the onset of cardiac slowing by intracisternal NE was more rapid than intraventricular NE. 4) Upon repeated administration of NE at the intervals of about two hours, blood pressure responses changed to the pressor ones, the cardiac slowing unchanged. By this procedure the cardiac slowing as well as the hypotension by clonidine were gradually diminished. 5) Clonidine, when given during the NE effects were persisting, did not produce the lowering of blood pressure and further decrease of heart rate. NE, when given during the clonidine effects were persisting, produced marked elevation of blood pressure but did not produce further decrease of heart rate. 6) After intraventricular administration of regitine or desmethylimipramine, the cardiac slowing effect of NE and the clonidine effects were not observed, whereas NE produced marked elevation of blood pressure. 7) Reserpinized rabbits showed pressor and cardiac accelerating responses to NE; slight pressor, and little cardiac responses to clonidine. 8) It seems that the cardiac slowing by both clonidine and NE as well as the hypotetsion by clonidine are mediated by the presynaptic ${\alpha}$-adrenoceptor in the brain but the pressor responses to NE and clonidine are mediated by other site(s) than the presynaptic ones.

• Journal of fish pathology
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• v.14 no.1
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• pp.31-36
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• 2001

A novel clonidine binding sites were characterized in the intestinal membrane isolated from seawater eels, Anguilla japonica. The specific clonidine binding sites consisted of at least two classes, high affinity ($K_d=1.4{\pm}0.3$ nM n = 5) and low affinity ($K_d=175{\pm}34$ nM n = 5) sites. The specific binding of 2 nM [$^3H$]clonidine was most enhanced at $20^{\circ}C$ and pH 7.5, and reversed by unlabelled clonidine. Such binding was hardly inhibited by adrenaline, yohimbine or rauwolscine, indicating that most binding sites are distinct from $\alpha_2$-adrenoceptor. The specific clonidine binding sites was inhibited by various imidazoline/guanidinium drugs, indicating existence of imidazoline/guanidinium receptive sites (IGRS) or imidazoline receptors in the eel intestine. Competition experiments revealed that rank order to displace 2 nM [$^3H$]clonidine from their binding sites was as follows : guanabenz > cirazoline = naphazoline = UK14,304 = ST587 $\geq$ clonidine $\geq$ idazoxan = RX821002 = tolazoline > ST93 = oxymetazoline = amiloride = ST91 > yohimbine = efaroxan = rauwolscine $\geq$ adrenaline = ST567 = histamine = agmatine. Although physiological role of IGRS is not clear yet even in mammalian cell/tissues, eel intestine may be a good model to elucidate how the IGRS act in the cell and to decide what is the endogenous ligand for the IGRS.

• The Korean Journal of Pharmacology
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• v.18 no.1
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• pp.33-41
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• 1982

In this paper, the influences of adrenergic blockades; propranolol and phenoxybenzamine on the changes of hyperglycemic action, hepatic glycogen content, and brain norepinephrine (NE) content induced by clonidine were investigated in the male mice. The results obtained were summarized as follows: 1) Blood glucose level was significantly increased by clonidine $(30{\mu}g/kg)$. The increase of blood glucose level induced by clonidine was not affect by the propranolol (10mg/kg) pretreatment, but significantly inhibited by the phenoxybenzamine (10mg/kg) pretreatment. 2) Hepatic glycogen content was moderately inhibited by clonidine. The decrease of hepatic glycogen content induced by clonidine was not affected by the propranolol and phenoxybenzamine pretreatment. 3) Brain NE content was significantly increased in 30 minutes and 60 minutes after clonidine treatment. The increase of brain NE content induced by clonidine was significantly inhibited by the phenoxybenzamine pretreatment. The increase of train NE content induced in 90 minutes and 120 minutes after clonidine treatment was more markedly increased by the propranolol pretreatment.