• 약학회지
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• 제32권4호
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• pp.258-273
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• 1988

In this study attempts were made to observe the effects of guanabenz on renal function in dog, which manifests the antihypertensive action by inhibition of sympathetic tone through stimulating the presynaptic adrenoceptor (${\alpha}_2-adrenoceptor$). Guanabenz, when injected at a dose of $30.0{\mu}g/kg$, or infused at a dose of $3.0{\mu}g/kg/min$ intravenously, produced diuretic action with increased amounts of $Na^+\;and\;K^+$ in urine, and with decreased reabsorption rates of $Na^+\;and\;K^+$ in renal tubules. It was also observed that the rates of osmolar and free water clearances were increased, but the glomerular filtration rate and renal plasma flow were not changed. Guanabenz injected at a dose of $3.0{\mu}g/kg$ into a carotid artery or infused intravenously at a dose of $3.0{\mu}g/kg/min$ in a state of water diuresis elicited the diuretic action of the similar aspect as a case of guanabenz given intravenously. The diuretic action produced by guanabenz was completly blocked by pretreatment of i.v. prazosin, ${\alpha}_1-adrenoblocking$ agent, or of i.v. yohimbine, ${\alpha}_2-adrenergic$ blocking agent. Prazosin, when given into a renal artery, inhibited the diuretic action by i.v. guanabenz in only injected kidney, whereas in case of yohimbine the action was inhibited in both kidney. Guanabenz infused at a dose of $1.0{\mu}g/kg/min$ into a renal artery exhibited no significant changes of renal function in both kidney. In denervation experiments, guanabenz given intravenously produced typical diuretic action in innervated kidney, whereas in denervated kidney, it did not affect the action at initial period but exhibited the action with increase of only free water clearance at later period. These results suggest that guanabenz produced diuretic action in dog by inhibition of electrolyte reabsorption rates in renal tabules, mainly proximal tubule and of ADH release, which is mediated by stimulating of central sympathetic ${\alpha}_2-receptor$.

• 대한약리학회지
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• 제22권2호
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• pp.115-122
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• 1986

Urethane 마취 가토에서 뇌내 alpha-1및 alpha-2 adrenoceptor의 작용에 미치는 calcium antagonist의 영항을 알아보고자 뇌실내 methoxamine과 clonidine의 혈압및 심박수 변동에 미치는 diltiazem, nifedipine의 영향을 조사한 결과, 1). 뇌실내 methgramine(1mg)은 혈압상승및 심박수 감소를 일으켰고, 뇌실내 clonidine$(30{\mu}g)$은 혈압하강및 심박수 감소를 일으켰다. 2). 뇌실내 diltiazem과 nifedipine은 dose-dependent한 혈압하강을 일으켰으며 심박수 감소를 일으켰다. Diltiazem에 비하여 nifedipine은 혈압하강 효과는 크고 심박수 감소효과는 작았다. 뇌실내 diltiazem$(400{\mu}g)$, nifedipine$(35{\mu}g)$의 혈압하강 작용은 완만하고 지속적이었으나 같은 양의 정맥내 투여효과는 일과성이었다. 3). 뇌실내 diltiazem$(400{\mu}g)$이나 nifedipine$(35,\;350{\mu}g)$ 처리 후에 methoxamine(1mg)의 혈압상승 효과는 영향받지 않았으나 심박수감소 효과는 유의하게 감약되었다. 4). Clonidine의 혈압하강 작용은 뇌실내 diltiazem$(400{\mu}g)$이나 nifedipine$(35,\;350{\mu}g)$ 처리 후에 감약되었으나 정맥 내 diltiazem$(200{\mu}g/kg)$이나 nifedipine$(30{\mu}g/kg)$ 후에는 영향받지 않았다. Clonidine의 심박수 감소작용은 .뇌실내및 정맥내 diltiazem이나 nifedipine 처리후에 감약되었다. 5). 뇌실내 clonidine$(30{\mu}g)$ 처 리후 뇌실내 diltiazem$(400{\mu}g)$과 nifedipine$(350{\mu}g)$의 혈압하강및 심박수 감소효과는 영향 받지 않고 그대로 나타났다. 이상의 결과로 diltiazem과 nifedipine은 가토뇌내에서 methoxamine에 의한 혈압상승의 작용점인 alrfia-1 adrenoceptor의 흥분에는 영향을 미치지 못하나 clonidine의 작용점인 alpha-2 adrenoceptor의 흥분에 의한 혈압하강및 심박수 감소효과는 억제한다고 추론하였다.

• Archives of Pharmacal Research
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• 제19권6호
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• pp.456-461
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• 1996

Vascular relaxation action of crude extracts of two kinds of Coptidis rhizoma (Coptis chinensis and Coptis japonica, Ranunculaceae) was investigated and compared with that of berberine and palmatine, active alkaloid components of these plants. The results show that total extracts, berberine, and palmatine induced a concentration-dependent vasodilatation of rat thoracic aorta contracted with phenylephrine (PE). Palmatine, unlike to berberine, did not inhibit contraction induced by KCI. In calcium-free media, not only berberine but also crude extracts inhibited calcium-induced contraction. Furthermore, pretreatment of crude extracts inhibited contraction induced by PE noncompetitively. In PE-induced contraction, berberine was 2.5 times more potent than Coptis chinensis in the relaxation of rat aorta in terms of $IC_{50}$ values. Analysis of the effects of crude extracts on the Emax and $IC_{50}(PE)IC_{50}(KCI)$ ratios provides information on selectivity and indicates that extracts exhibit greater inhibition of the contrac tile response induced by PE than by KCI. We concluded that crude extracts have .alpha.-adrenoceptor blocking action and possesses inhibitory effect on calcium influx, which may be at least in part responsible for the antihypertensive action.

• 대한약리학회지
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• 제19권1호
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• pp.123-131
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• 1983

1) Urethane 마취가토(痲醉家兎)에서 경뇌막외강내(硬腦膜外腔內)에 삽입(揷入)한 balloon을 통(通)한 가압(加壓) 및 두개내압기종방법(頭蓋內壓記種方法)에 의하여 내압(內壓)을 상승(上昇)시키고, 이 내압상승(內壓上昇)에 따른 혈압상승(血壓上昇)에 미치는 ${\alpha}_2-adrenoceptor$ antagonist인 yohimbine의 영향(影響)을 관찰(觀察)하였다. 2) 내압(內壓)은 가압(加壓)balloon 내(內) 식염수주입(食鹽水注入)으로 주입초기(注入初期) 에는 완만(緩慢)하게 그 후 점차(漸次) 급격(急激)하게 상승(上昇)하였다. 이에 따라 혈압(血壓)은 처음에 경미(輕微)한 하강경향(下降傾向)을 보인 후 급격(急激)하게 상승(上昇)하였고, 더욱 내압(內壓)을 상승(上昇)시키면 혈압(血壓)은 심(甚)한 하강(下降)을 보였다. 최고혈압상승정도(最高血壓上昇程度)는 원혈압(元血壓)의 $49{\pm}2.4%$(32예(例) 평균(平均)${\pm}SE)$의 증가(增加)였으며, 이때에 가압(加壓)balloon 내(內)로 주입(注入)된 식염수양(食鹽水量)은 $1.22{\pm}0.15\;ml$, 내압(內壓)은 $165{\pm}6.4\;mmHg$였다. 3) 측뇌실내(側腦室內) yohimbine$(50{\mu}g)$은 혈압자체(血壓自體) 영향(影響)을 미치지 못하였으나, 본양(本量)의 yohimbine 투여후(投與後)에는 가압(加壓)balloon내(內)에 대조동물(對照動物)에서보다 훨씬 적은 양(量)의 식염수주입(食鹽水注入)으로 내압(內壓) 및 혈압(血壓)이 상승(上昇)하였다. 즉(卽) 최고혈압상승(最高血壓上昇) (6예평균(例平均, $57{\pm}4.5%)$이 나타날 때의 가압(加壓)balloon 내(內)에 주입된 식염수양(食鹽水量)은 $0.83{\pm}0.02\;ml$, 내압(內壓)은 $164{\pm}9.6\;mmHg$였다. 4) $Clonidine(30\;{\mu}g)$의 측뇌실내(側腦室內) 주입후(注入後) 혈압자체(血壓自體)는 하강(下降)되었고 이때 가압(加壓)balloon 내 식염수주입(食鹽水注入)에 의한 내압상승(內壓上昇)은 대조군(對照郡)보다 순화(純化)되었으며 혈압상승(血壓上昇)은 거의 볼 수 없었다. 5) $Clonidine(30\;{\mu}g)$투여(投與)로 하강(下降)된 혈압(血壓)은 $yohimbine(500\;{\mu}g)$투여(投與)로 거의 원혈압(原血壓)으로 회복(回復)되었고, 이때 내압(內壓)을 상승(上昇)시키면 대조군(對照郡)에서와 같은 내압상승(內壓上昇)에 따른 혈압상승(血壓上昇)이 나타났다. 6) 본실험(本實驗) 성적(成績)은 가토(家兎)에서 ${\alpha}_2-adrenoceptor$ antagonist가 뇌(腦)에 존재(存在)할 때는 두개뇌압상승(頭蓋腦壓上昇)에 따른 혈압상승(血壓上昇)이 촉진(促進)되고 또한 ${\alpha}_2-adrenoceptor\;agonist$에 의한 두개뇌압상승(頭蓋腦壓上昇)에 따른 혈압상승(血壓上昇)의 억제(抑制)가 나타나지 않음을 가리키고 있다.

• 대한약리학회지
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• 제32권2호
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• pp.189-199
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• 1996

Myocardial ${\alpha}_1-adrenoceptors$ have been shown to mediate a biphaslc inotropic response that was characterized by a transient decline followed by a sustained increasing phase in guinea pig ventricular muscle. Recently one group reported that an ${\alpha}_1-adrenoceptors-induced$ intracellular $Na^+$ decrease is linked to fast $Na^+$ channel inhibition and another group reported that it is linked to $Na^+$-$K^+$ pump activation by ${\alpha}_{1b}-adrenoceptors$. But until now, its mechanism is not clear. Therefore, to see whether the $Na^+$channel or $Na^+-K^+$ pump is related to a decrease in intracellular $Na^+$ activity and/or the negative inotropic response, and which ${\alpha}_1-adrenoceptor$ subtype was involved in the decrease in intracellular $Na^+$activity by phenylephrine, we used conventional and sodium selective microelectrodes, and tension transducer to determine the effects of ${\alpha}_1-adrenergic$ stimulation on membrane potential, intracellular $Na^+$ activity, and twitch force in guinea pig ventricular muscles. $10^{-5}$ M Phenylephrine produced a slight hyperpolarization of the diastolic membrane potential, a decrease or increase in $a_N^i_a$, and a biphasic inotropic response. The negative inotropic response accompanied by a decrease in intracellular $Na^+$activity, whereas in muscles showing a remarkable positive inotropic response without initial negative inotropic effect was accompanied by an increase in intracellular $Na^+$ activity. The decrease in intracellular $Na^+$ activity was apparently inhibited by WB4101, an antagonist of the ${\alpha}_{1a}-adrenoceptors$. The decrease in intracellular $Na^+$ activity caused by phenylephrine was not abolished or reduced by a block of the fast $Na^+$ channels. $V_{max}$ also was not affected by phenylephrine. Phenylephrine produced an increase in intracellular $Na^+$ activity in the presence of a high concentration of extracellular $Ca^{2+}$ (in quiescent muscle) or phorbol dibutyrate, a protein kinase C activator(in beating muscle). These suggest that the ${\alpha}_{1a}-adrenoceptors-mediated$ decrease in intracellular $Na^+$ activity may be related to the protein kinase C.

• The Korean Journal of Physiology and Pharmacology
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• 제3권4호
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• pp.383-391
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• 1999

This study was carried out to determine whether the effects of an ${\alpha}_2-adrenoceptor$ agonist, clonidine, on mean arterial pressure (MAP) and heart rate (HR) are influenced by mild hypothermia. Experiments were performed in respiration-controlled and spontaneously breathing pentobarbital-anesthetized rats. Rectal temperature was maintained at $37.5{\pm}0.3^{circ}C$ for normothermic groups or at $35.2{\pm}0.3^{circ}C$ for mild hypothermic groups. Intravenous injection of clonidine (1 and 2 ${\mu}g/kg)$ produced depressor and bradycardic responses in spontaneously breathing rats under both normothermic and mild hypothermic condition: a decrease in MAP was not altered but bradycardic response was significantly augmented in the mild hypothermic group as compared with the normothermic group. Under the respiration-controlled condition, the hypotensive effect of clonidine $(2\;{\mu}g/kg)$ was reduced, whereas the bradycardic effect was increased in mild hypothermic rats as compared with normothermic rats. Both hypotensive and bradycardic effects of clondine $(2\;{\mu}g/kg)$ were blocked by pretreatment with an ${\alpha}_2-adrenoceptor$ antagonist, yohimbine (0.5 mg/kg), in both thermal conditions. Yohimbine (0.5 mg/kg, i.v.) alone produced signifcantly an increase in heart rate in the mild hypothermic group than in the normothermic group. Pretreatment with a muscarinic receptor antagonist, atropine methylnitrate (1 mg/kg, i.v.), attenuated the bradycardic effect of clonidine in the mild hypothermic group but not in the normothermic group. These results suggest that clonidine- induced bradycardia is amplified by mild hypothermia probably through an increased parasympathetic activity.

• 대한수의학회지
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• 제34권3호
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• pp.479-486
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• 1994

Effects of catecholamines and the site of receptor of catecholamines were investigated in the longitudinal muscle of the rumen. In order to this experiment, specimens were obtained from 35 Korean Native Cattles, 2-3 years old, in the Kwang-ju area slaughterhouse. Longitudinal muscle strips of rumen were made from sample, and then measured the isometric contraction with physiograph in $37{^{\circ}C}$ organ bath. The results were summarized as follows. 1. 30% of all strips showed rhythmic contraction after short incubation time. 2. Relaxation produced by catecholamines in this preparations increased in a dose-dependant manner. 3. Isoproterenol(${\beta}$-agonist) caused relaxation, but phenylephrine(${\alpha}_1$-agonist) and xylazine(${\alpha}_2$-agonist) were unaffected. 4. The relaxation induced by epinephrine and norepinephrine were not affected by phentolamine(${\alpha}$-blocker) and prazosin(${\alpha}_1$-blocker), yohimbine(${\alpha}_2$-blocker). But propranolol(${\beta}$-antagonist) abolished the effect of catecholamines on relaxation. 5. It is concluded that catecholamines produced relaxation in the longitudinal muscle of rumen via the ${\beta}$-adrenoceptor.

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 1997년도 학술발표회
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• pp.27-27
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• 1997

The effects of $a_1$-adrenoceptor stimulation on intracellular $Ca^{2+}$ ([C $a^{2+}$]$_{i}$ ) transient, contraction, and L-type $Ca^{2＋}$ current ( $I_{Ca,L}$) were studied in single cells isolated from ventricles of guinea pig hearts. Phenylephrine, $\alpha$$_1$-adrenergic agonist, (5$\times$10$^{-5}$ ~10$^{-4}$ M) produced a biphasic pattern of inotropism： transient negative response (decrease in contraction by 23.9$\pm$2.5% of control) followed by a sustained positive response (increase in contraction by 60.0$\pm$3.4%, mean $\pm$ SD, n=12).(omitted)ted)

• 대한수의학회지
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• 제28권1호
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• pp.23-28
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• 1988

To examine the selectivity of diltiazem, used in the cardiovascular diseases, on alpha-1 and alpha-2 adrenoceptor-induced pressor responses, effect of diltiazem on alpha-adrenocepter agonist-induced pressor responses were investigated in urethane-anesthetized rabbits and spinal rabbits. The results are summarized as follows: 1. Intravenous diltiazem(10, 30, 100, 300, $1000{\mu}g/kg$) produced dose-dependent depressor response in rabbits. 2. Pressor responses to intravenous norepinephrine($10{\mu}g/kg$) and phenylephrine ($30{\mu}g/kg$) were inhibited by pretreatment with intravenous diltiazem in rabbits and no difference was noted between the degree of both inhibitions of the pressor response by diltiazem. 3. Presser responses to intravenous norepinephrine ($3{\mu}g/kg$), phenylephrine ($20{\mu}g/kg$) and clonidine ($300{\mu}g/kg$) were inhibited by pretreatment with intravenous diltiazem in spinal rabbits. No difference was noted between the inhibition of norepinephrine-induced pressor response and that of phenylephrine-induced pressor response by diltiazem. The inhibition of clonidine-induced pressor response by diltiazem was slightly prominent than that of norepinephrine- or phenylephrine-induced pressor response. These results suggest that diltiazem significantly inhibits both pressor responses mediated by alpha-1 and alpha-2 adrenoceptors.

• Journal of Dental Anesthesia and Pain Medicine
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• 제19권2호
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• pp.83-90
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• 2019

Dexmedetomidine is a highly selective ${\alpha}2$-adrenoceptor agonist with a vast array of properties, making it suitable for sedation in numerous clinical scenarios. Its use was previously restricted to the sedation of intensive care unit patients. However, its use in pediatric dental sedation has been gaining momentum, owing to its high suitability when compared with conventional pediatric sedatives. Its properties range from sedation to anxiolysis to analgesia, due to its sympatholytic properties and minimal respiratory depression ability. Because dexmedetomidine is an efficacious and safe drug, it is gaining importance in pediatric sedation. Thus, the aim of this review is to highlight the properties of dexmedetomidine, its administration routes, its advantages over the commonly used pediatric sedatives, and especially its role as an alternative pediatric sedative.