• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.245.2-245.2
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• 2003

A rapid and reproducible high performance liquid chromatographic assay of prazosin in human plasma was developed. After addition of internal standard (IS, terazosin hydrochloride) and alkalization of the plasma, the drug and IS were extracted into t-butylmethylether. The organic phase was back-extracted with 0.05% phosphoric acid and 50 ${\mu}$l of the acid solution was injected into a reverse-phase C18 column with a mobile phase consisting of water: acetonitrile: triethylamine = 75 : 25 : 0.1 (pH 5.0). (omitted)

• The Korean Journal of Physiology and Pharmacology
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• 제25권6호
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• pp.525-532
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• 2021

We have investigated the relative roles of α₁-adrenoceptors and purinoceptors in contractions to low and high frequency stimulation of the mouse vas deferens, in terms of the time course of responses. In separate experiments, isometric contractile responses were obtained to 10 pulses at 1 Hz and 40 pulses at 10 Hz. Responses to 1 Hz stimulation consisted of a series of discrete peaks. The α_1A-adrenoceptor antagonist RS100329 (10^-9M-10^-7M) significantly reduced the response to the first pulse, the α_1D-adrenoceptor antagonist BMY7378 (10^-7M-10^-6M) significantly reduced the response to the first two pulses, and the non-selective α₁-adrenoceptor antagonist prazosin (10^-8M) reduced the response to the first 4 pulses at 1 Hz. Responses to 10 Hz stimulation consisted of an early peak response and a maintained plateau response. RS100329 significantly reduced the peak response but did not significantly affect the plateau response. Prazosin, significantly reduced both the peak and plateau responses. The α_1A-adrenoceptor antagonist RS17053 in high concentrations reduced mainly the plateau response leaving a clear early peak response. The plateau response of contraction was almost abolished by the purinoceptor antagonist suramin. These results suggest that there is a relatively minor early α_1D-adrenoceptor and a larger early α_1A-adrenoceptor component to stimulationevoked contractions of mouse vas deferens, but the major α₁-adrenoceptor component is revealed by prazosin to be α_1B-adrenoceptor mediated. α_1B-Adrenoceptor activation probably facilitates contractions mediated by other α₁-adrenoceptors and by purinoceptors. These results suggest that combined non-selective α₁-adrenoceptor blockade, particularly α_1B-adrenoceptor blockade, in addition to P2X1-purinoceptor blockade is useful in reducing male fertility.

• 대한약리학회지
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• 제21권2호
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• pp.90-98
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• 1985

새앙쥐 강제수영 실험에서 부동자세 시간의 단축은 향주도성 행동의 항진이라는 본능적 충동의 유발이라는 가정 아래 중추 noradrenaline neuron에 있어서 ${\alpha}_1$- 및 ${\alpha}_2$-adrenoceptor의 역할과 관련지어 이 실험을 행하였고 다음과 같은 결론을 얻었다. 1. 새앙쥐를 이용한 강제수영 실험에서 부동자세 시간은 clonidine 및 guanabenz 등과 같은 ${\alpha}_2$-agonists에 의하여 용량에 의존하여 단축되었다. B-HT 933 및 oxymetazoline은 용량에 의존하지 않으나 단축시켰다. xylazine에의하여는 오히려 증가되었다. 2.${\alpha}_1$-Agonists 인 cirazoline, amidephrine 및 methoxamine은 부동자세 시간에 일관성 있는 영향을 미치지 아니하였다. 3. Clonidine과guanabenz에 의한 부동자세 시간의 단축은 ${\alpha}_2$-antagonists, yohimbine, idazoxan 및 phentolamine 전처치로 봉쇄되었으나 ${\alpha}_1$-antagonists, prazosin 및 corynanthine에 의하여는 영향을 받지 아니하였다. 4, d-Amphetamine 투여시 부동자세 시간은 용량에 비례하여 단축되었고, 이러한 단축효과는 yohimbine에 의하여는 길항되었으나 prazosin에 의하여는 영향을 받지 아니하였다. 5. ${\alpha}$-methyl-p-tyrosine 이나 reserpine 또는 두 약물을 동시에 전처치 하였을때 clonidine에 의한 부동자세 시간의 단축은 영향을 받지 아니하였다. 6. Desipramine 및 imipramine 같은 항우울제를 장기처치 또는 장기간 저기충격 요법을 가한 새앙쥐에서도 clonidine의 효과는 영향을 받지 아니하였다. 이상의 결과로 보아 새앙쥐의 강제수영 실험에서의 부동자세 시간의 변동은 중추내 noradrenergic neuron의 postsynaptic ${\alpha}_2$-adrenoceptor와 밀접한 관련이 있다고 시사되며 이러한 ${\alpha}_2$-agonists에 의하여 항진되는 escape-directed behavior는 자기보호를 위한 일종의 충동의 유발로 인한 행동으로 사료된다.

• 대한약리학회지
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• 제20권2호
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• pp.7-14
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• 1984

뇌척수제거 흰쥐에서 clonidine정맥주사에 의한 확장기 혈압상승작용(postsynaptic action)과 전기자극으로 야기된 빈맥의 심막충수 감소작용(presynaptic inhibitory action)에 대하여 ${\alpha}_1-$ 및 ${\alpha}_2-adrenoceptor$ 길항제의 영향을 관찰하였다. 삼환계 항우울약물인 imipramine을 단회 및 장기 투여하였을 때 clonidine에 의한 두 작용이 어떻게 영향을 받는가를 관찰하여 다음과 같이 요약하였다. 1) Clonidine의 혈압상승효과는 phentolamine이나 piperoxan 전처치에 의하여 길항되었으나, prazosin 전처치에 의하여는 길항되지 아니하였다. 2) Clonidine의 빈맥에 대한 억제작용은 prazosin에 의하여는 영향을 받지 아니하였으나, phentolamine 및 piperoxan 전처치에 의하여는 길항되었다. 3) Clonidine에 대한 혈압상승반응은 imipramine(20 mg/kg) 단회 및 장기 투여에 의하여 차단되었으며, 전자에서 보다 후자에서 더 현저하였다. 4) 빈맥에 대한 clonidine의 억제작용은imipramine단회 및 장기 투여에 의하여 모두 차단되었고, 양자간 에는 큰 차이가 없었다. 이상의 결과로 presynaptic ${\alpha}_2-adrenoceptor$는 imipramine 단회 투여에 의하여 억제되었고 장기 투여에 의하여는 pre- 및 postsynaptic ${\alpha}_2-adrenoceptor$ 둘 다 현저히 억제되었다. 이런 점으로 미루어 presynaptic ${\alpha}_2-adrenoceptor$의 감수성 저하가 삼환계 항우울제의 직접적인 작용기전일 것이라는 증거를 제시하기는 어렵다고 암시된다.

• 생약학회지
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• 제21권2호
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• pp.173-178
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• 1990

This study was attempted to examine the effect of Sopung-Tang(SPT) on the arterial blood pressure in rats and to elucidate its mechanism of action. SPT given into a femoral vein produced a dose-related vasopressor responses followed by vasodepressor responses. SPT-induced hypotension was significantly inhibited by pretreatment with atropine or propranolol while was not affected by chlorisondamine, Prazosin and cyproheptadine. SPT-evoked hypertensive activity was markedly blocked by pretreatment with prazosin but was not influenced by atropine, chlorisondamine, propranolol and cyproheptadine. Infusion of SPT(15.0 mg/kg/30min) did not affect norepinephrine-induced pressor responses. These experimental results suggest that SPT causes biphasically initial hypertensive activity followed by hypotensive activity, and that this hypertension may be due to the stimulation of peripheral adrenergic alpha-receptors and hypotension may be elicited through stimulation of peripheral cholinergic muscarinic receptors and adrenergic beta-receptors.

• The Korean Journal of Physiology and Pharmacology
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• 제2권1호
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• pp.55-62
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• 1998

${\alpha},\;{\beta}-Adrenergics$, and calcium channels were known to be related to inducing cardiac hypertrophy. Recently, it was reported that the cardiac renin-angiotensin system (RAS) was an important factor in ventricular hypertrophy. The present study was aimed to investigate the effects of ${\alpha},\;{\beta}-adrenergic$, and calcium channel blockers that might be involved in the regulation of cardiac RAS. The reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of renin gene in the perfused rat heart. Changes in angiotensin converting enzyme (ACE) activity and cyclic AMP (cAMP) content which were thought to play a role in inducing cardiac hypertrophy were measured in the perfused rat heart. The expression of renin gene was not only increased by isoproterenol with metoprolol-pretreatment but also increased by vasopressin treatment in the presence of calcium channel blocker, nifedipine or verapamil. Either prazosin alone or norepinephrine with prazosin-pretreatment significantly increased the ACE activity. However, isoproterenol with metoprolol-pretreatment significantly decreased the ACE activity. On the other hand, the ACE activity was not changed by vasopressin, nifedipine, or verapamil treatments. The content of cAMP was significantly increased by either isoproterenol or vasopressin treatment. According to these results, renin gene expression was associated with ${\beta}2$ - adrenoceptor and calcium channel. ACE activity was associated with ${\alpha}-\;and{\beta}2$ - adrenoceptor. In conclusion, ${\beta}2$ - adrenoceptor was important in cardiac renin gene expression and ACE activity and ${\alpha},\;{\beta}$ -adrenergic, and calcium channel blockers might be involved in the regulation of cardiac RAS in a complicated way.

• Journal of Chest Surgery
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• 제23권6호
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• pp.1107-1117
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• 1990

The regulatory role of the post \ulcorner1-and \ulcorner2-adrenoceptors on cardiac function, particularly in coronary flow rate, was investigated in the isolated rat heart treated with 10-6 M propranolol. When introduced into the left atrium of the heart, phenylephrine[10-7-10-2 M] decreased coronary flow rate and increased mean coronary resistance in a dose related fashion, but did not affect heart rate. Methoxamine also elicited the increment of coronary resistance and the decrement of coronary flow rate, though the effects of methoxamine were weaker than those by phenylephrine. The effect of phenylephrine was inhibited by 1\ulcornerM prazosin and shifting the dose-response curve to the right. The effects of clonidine, a selective \ulcorner2-adrenoceptor agonist, were studied in the heart taken from reserpinized rats. Clonidine increased coronary resistance, decreased heart rate and coronary flow rate with a dose-dependent manner. These effects were abolished by 10-6 M yohimbine, a selective \ulcorner2-antagonist, and were not affected by 10-6M prazosin. Clonidine also decreased coronary flow and increased mean coronary resistance in electric paced heart. These effects were inhibited by rawoulscine, a selective ca-antagonist. These results indicate that the stimulation of both post \ulcorner1-and \ulcorner2-adrenoceptor causes coronary vasoconstiction. And it is inferred that this model of sympathomimetics-induced coronary vasospasm may provide a useful tool for investigating spasmolytic agents which are of benefit in the treatment of variant angina.

• The Korean Journal of Physiology and Pharmacology
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• 제2권6호
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• pp.753-761
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• 1998

Preconditioning of a heart with small doses of catecholamines induces a tolerance against the subsequent lethal ischemia. The present study was performed to find a specific receptor pathway involved with the catecholamine preconditioning and to test if adenosine plays a role in this cardioprotective effect. Isolated rat hearts, pretreated with small doses of ${\alpha}-\;or\;{\beta}-adrenergic$ agonists/antagonists, were subjected to 20 minutes ischemia and 20 minutes reperfusion by Langendorff perfusion method. Cardiac mechanical functions, lactate dehydrogenase and adenosine release from the hearts were measured before and after the drug treatments and ischemia. In another series of experiments, adenosine $A_1\;or\;A_2$ receptor blockers were treated prior to administration of adrenergic agonists. Pretreatments of a ${\beta}-agonist,\;isoproterenol(10^{-9}{\sim}10^{-7}\;M)$ markedly improved the post-ischemic mechanical function and reduced the lactate dehydrogenase release. Similar cardioprotective effect was observed with an ?-agonist, phenylephrine pretreatment, but much higher $concentration(10^{-4}\;M)$ was needed to achieve the same degree of cardioprotection. The cardioprotective effects of isoproterenol and phenylephrine pretreatments were blocked by a ${\beta}_1-adrenergic$ receptor antagonist, atenolol, but not by an ${\alpha}_1-antagonist,$ prazosin. Adenosine release from the heart was increased by isoproterenol, and the increase was also blocked by atenolol, but not by prazosin. A selective $A_1-adenosine$ receptor antagonist, 1,3-dipropyl-8-cyclopentyl xanthine (DPCPX) blocked the cardioprotection by isoproterenol pretreatment. These results suggest that catecholamine pretreatment protects rat myocardium against ischemia and reperfusion injury by mediation of ${\beta}_1-adrenergic$ receptor pathway, and that adenosine is involved in this cardioprotective effect.

• Journal of Acupuncture Research
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• 제28권1호
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• pp.37-44
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• 2011

배경 및 목적 : 봉독약침요법(bee venom pharmacopuncture, BVP)은 rheumatoid arthritis(RA)의 치료에 활용되고 있으나, RA로 인한 염증성 통증에 대한 봉독약침의 진통효과와 specific mechanism은 아직까지 명확하게 밝혀지지 않았다. 이에 본 연구에서는 RA animal model로서 collagen-induced arthritis(CIA) rat model에서 봉독약침의 a1-adrenergic, 5HT-3 그리고 muscarinic cholinergic mechanism을 확인하고자 한다. 방법 : CIA를 유도하기 위하여 male Sprague-Dawley rat에 freund's incomplete adjuvant에 유화(乳化)시킨 bovine type II collagen을 주입하고 14일 후 booster injection 시행하였다. 진통효과는 tail flick latency (TFL)로 평가하였다. 결과 : 관절염의 유도 이후 염증성 통증 역치는 시간이 지나면서 낮아지며, 5주 이후로는 통증 역치에 큰 변화가 없이 유지되었다. 첫 번째 immunization으로부터 5주 경과 후 족삼리($ST_{36}$)에 봉독약침처치(0.25 mg/ kg)를 시행하여 유의한 진통효과를 관찰하였다. 또한 봉독약침의 진통효과는 ondansetron(5HT-3 receptor antagonist, 0.5mg/kg, i.p.), atropine(muscarinic cholinergic receptor antagonist, 1mg/kg, i.p.)의 전처치에 의하여 억제되었으나, prazosin(a1-adrenergic receptor antagonist, 1mg/kg, i.p.)의 전처치에 의해서는 억제되지 않았다. 결론 : 봉독약침은 CIA로 인한 염증성 통증에 유의한 진통효과를 나타내며 그 analgesic mechanism은 5HT-3와 muscarinic cholinergic receptor에 의하여 매개되며 a1-adrenergic receptor에 의하여 매개되지는 않았다.

• The Korean Journal of Physiology
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• 제29권2호
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• pp.203-216
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• 1995

The effects of ${\alpha}_1-adrenergic$ receptor stimulation on membrane potential, intracellular $Na^+$ activity, and twitch force were investigated in ventricular muscles from guinea-pig hearts. Action potentials, intracellular $Na^+$ activity, and twitch force of ventricular papillary muscles were measured simultaneously under various experimental conditions. Stimulation of the ${\alpha}_1-adrenergic$ receptor by phenylephrine produced variable changes in action potential duration, a slight hyperpolarization of the diastolic membrane potential, a decrease in intracellular $Na^+$ activity, and a biphasic inotropic response in which a transient negative inotropic response was followed by a sustained positive inotropic response. These changes were blocked by prazosin, an antagonist of the ${\alpha}_1-adrenergic$ receptor, but not by atenolol, an antagonist of the ${\beta}-adrenergic$ receptor. This indicates that the changes in membrane potential, intracellular $Na^+$ activity, and twitch force are mediated by stimulation of the ${\alpha}_1-adrenergic$ receptor, but not by stimulation of ${\beta}-adrenergic$ receptor. The decrease in intracellular $Na^+$ activity was not observed in quiescent muscles, depending on the rate of the action pontentials in beating muscles. The intracellular $Na^+$ activity decrease was substantially inhibited by tetrodotoxin. However, the decrease in intracellular $Na^+$ activity was not affected by an inhibition of the $Na^+-K^+$ pump. Therefore, the decrease in intracellular $Na^+$ activity mediated by the ${\alpha}_1-adrenergic$ receptor appears to be due to a reduction of $Na^+$ influx during the action potential, perhaps through tetrodotoxin sensitive $Na^+$ channels. Our study also revealed that the decrease in intracellular $Na^+$ activity might be related to the transient negative inotropic response. The intracellular $Na^+$ activity decrease could lower intracellular $Ca^{2+}$ through the $Na^+-Ca^{2+}$ exchanger and thereby produce a decline in twitch force.