• Biomolecules & Therapeutics
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• 제4권2호
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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.

• 생약학회지
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• 제21권1호
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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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• 제6권2호
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• pp.57-62
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• 1989

지연성 호흡저하의 위험성이 없으며 중추신경계에 작용하는 혈압강하제인 Clonidine을 경막외강으로 주입한 강우의 진통효과를 알아보고자 미추마취를 시행할 항문질환 환자 40명을 대상으로 I군(1.33% Lidocaine 15ml)과 II군(1.33% Lidocaine 15ml+Clonidine $75{\mu}g$.)으로 나누어 수술후 진통효과를 관찰해 보았던 바 다음과 같은 결론을 얻었다. 1. Lidocaine단독 주입한 I군에서는 평균 마취시간이 2.42시간이었다. 2. Clonidine $75{\mu}g$을 혼합 주입한 II군의 경우에는 평균 진통시간이 7.32시간이었다. 3. Clonidine을 혼합 주입한 미추마취경우에 진정제 정주로 환자가 수면상태로 된 후 심한 혈압강하 및 맥박감소가 있었으나 Clonidine의 효과인지 진정효과에 인한 변화인지는 알 수 없었으며 진정제를 투여하지 않은 경우에는 혈압강하 및 맥박 감소가 초래되지 않았다. 4. 수술후 Clonidine과 관련된 특별한 증상은 관찰되지 않았다. 이상의 결과로 보아 항문질환 수술후 특히 외래환자의 차원에서 술후 진통을 위한 방법으로는 지연성 호흡저하 및 뇨정체등의 부작용이 없는 Clonidine의 천골강내 투여방법이 바람직한 것으로 사료된다.

• Biomolecules & Therapeutics
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• 제1권2호
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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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• 제4권2호
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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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• 제7권2호
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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.

• 약학회지
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• 제27권4호
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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.

• 대한약리학회지
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• 제14권1_2호
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• pp.13-23
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• 1978

1) Urethane 마취가토(痲醉家兎)의 내뇌(腦內)(측뇌실(刻腦室) 또는 소뇌연수조내(小腦延髓槽內)에 norepinephrine (NE), clonidine을 주입(注入)할 때 일어나는 심박감소(心搏減少), 혈압하강(血壓下降)에 관한 이들 약물(藥物)의 작용점(作用點)을 조사(調査)할 것을 시도(試圖)하였다. 2) NE의 뇌내주입(腦內注入)은 심박감소(心搏減少)를 일으켰으나 혈압(血壓)에 미치는 영향(影響)은 뚜렷치 않았다. Clonidine은 심박감소(心搏減少), 혈압하강(血壓下降)을 일으켰다. 3) 측뇌실내주입(刻腦室內注入) 소뇌연수조내주입간(小腦延髓槽內注入間)에는 NE, clonidine, phenylephrine, isoproterenol의 심박(心搏), 혈압효과(血壓效果)에 차이(差異)가 없었다. 또 NE에 의한 심박감소효과(心搏減少效果)의 출현(出現)은 소뇌연수조내주입시(小腦延髓槽內注入時) 더 빨랐다. 4) 약(約) 2시간(時間) 간격(間隔)으로 NE를 반복(反復) 주입(注入)할 때 심박효과(心搏效果)에는 거의 변동(變動)이 없었으나 혈압효과(血壓效果)는 반복주입(反復注入)함에 따라 혈압상승효과(血壓上昇效果)가 현저(顯著)히 나타났다. Clonidine의 심박감소(心搏減少) 및 혈압하강효과(血壓下降效果)는 반복주입(反復注入)에 따라 점차 약화(弱化)되었다. 5) NE 주입후(注入後) NE 효과(效果)가 지속(持續)하고 있을 때 clonidine은 더 이상(以上)의 심박감소(心搏減少)를 일으키지 않고, 혈압하강(血壓下降)도 일으키지 않았다. Clonidine 주입후(注入後) clonidine 효과(效果)가 지속(持續)하고 있을 때 NE는 더 이상(以上)의 심박감소(心搏減少)를 일으키지 않았고 현저(顯著)한 혈압상승(血壓上昇)을 일으켰다. 6) Regitine 또는 desmethylimipramine의 뇌내주입후(腦內注入後) NE는 심박(心搏)에 거의 변동(變動)을 일으키지 않았으나 현저(顯著)한 혈압상승(血壓上昇)을 일으켰다. Clonidine은 심박(心搏), 혈압(血壓)에 거의 변동(變動)을 일으키지 않았다. 7) Reserpine 처리가토(處理家兎)에서는 NE는 심박증가(心搏增加)와 혈압상승(血壓上昇)을 일으켰으며, clonidine은 심박(心搏)에는 거의 변동(變動)을 일으키지 않았고 경미(輕微)한 혈압상승(血壓上昇)을 일으켰다. 8) NE 및 clonidine에 의한 심박감소(心搏減少), clonidine에 의한 혈압하강(血壓下降)은 주(主)로 presynaptic ${\alpha}$-adrenoceptor를 중개(仲介)하여 일어나나, NE 및 clonidine에 의한 혈압상승(血壓上昇)은 presynaptic site 이외(以外)의 부위(部位)를 중개(仲介)하여 일어나는것 같다.

• 한국어병학회지
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• 제14권1호
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• pp.31-36
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• 2001

해수에 적응된 뱀장어, Anguilla japonica의 장 세포막으로부터 새로운 clonidine의 결합부위가 있음이 밝혀졌다. Clonidine의 특이적인 결합부위는 적어도 2개의 부위 (high affinity $K_d=1.4{\pm}0.3$ nMn= 5, low affinity $K_d=175{\pm}34$ nM)를 가지고 있었다. 2nM [$^3H$]clonidine의 특이적인 결합은 $20^{\circ}C$, pH 7.5에서 최적 결합능을 가지고 있었고, 라벨되지 않은 clonidine에 의해 가역적인 반응을 보였다. 이러한 결합은 adrenaline, yohimbine과 rauwolscine에 의한 저해능은 약하였다. 그리고 대부분의 결합부위는 $\alpha_2$-adrenoceptor와는 상이하였다. Clonidine의 특이적인 결합은 다양한 imidazoline/guanidinium약물에 의해 억제되었다. Competition 실험의 결과, 2nM[$^3H$]clonidine의 치환 rank order는 다음과 같다. guanabenz > cirazoline = naphazoline=UK14,304= ST587 $\geq$ clonidine $\geq$ idazoxan = RX821002 = tolazoline > ST93 = oxymetazoline = amiloride = ST91 > yohimbine = efaroxan = rauwolscine $\geq$ adrenaline = ST567 = histamine = agmatine. 이러한 순서는 포유류에 분류된 imidazoline receptorl($I_1$), imidazoline receptor 2($I_2$) 및 imidazoline/guanidinium receptive sites(IGRS)형태와는 틀리기 때문에 새로운 imidazoline receptor라고 생각된다. 지금까지 보고된 포유류의 세포와 조직에서 IGRS의 생리학적인 역할은 명확하지 않지만, 해수뱀장어 장은 IGRS의 세포에 있어서의 역할 그리고 IGRS의 내인성(內因性) ligand가 무엇인가에 대한 좋은 모델이 될 수 있다고 생각되어진다.

• 대한약리학회지
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• 제18권1호
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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.