• 약학회지
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• 제35권5호
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• pp.416-426
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• 1991

The effects of an irreversible or a reversible $\alpha_1$-adrenoceptor antagonist (dibenamine or prazosin) on $\alpha_1$-adrenoceptor-mediated vasoconstrictions were studied in the endothelium-denuded rat aorta. In these experiments, the mobilization of intracelluier calcium and translocation of extracellular calcium were also studied. To exclude the modulation of endothelium releasing EDRF and EDCF, the endothelium was removed in all rat aortas. Contraction induced by phenylephrine (a full $\alpha_1$-adrenoceptor agonist) was separated into a fast phasic component of the response due to the release of intracellular calcium and a slow tonic one due to the influx of extracellular calcium. Pretreatments with increasing doses of reversible $\alpha_1$-adrenoceptor antagonist prazosin, as well as irreversible $\alpha_1$-adrenoceptor antagonist dibenamine, inhibited the phasic component of phenylephrine-induced contraction more effectively than the tonic one. Pretreatment of dibenamine (0.2 $\mu{M}$) or prazosin (10 nM) to the rat aorta abolished phasic response but remained tonic one about 41% and 51%, respectively. These results suggest that as the efficiency of phenylephrine was progressively reduced by pretreatments with increasing doses of an irreversible or a reversible $\alpha_1$-adrenoceptor antagonist (dibenamine or prazosin), the contraction induced by phenylephrine became progressively more dependent on the influx of extracellular calcium.

• 한국동물위생학회지
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• 제17권3호
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• pp.255-263
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• 1994

To elucidate the action of the adrenergic nerve on the isolated uterine smooth muscle of the pig, effects of electrical transmural nerve stimulation and norepinephrine were investigated on the pretreatment of phentolamine ； non-selective ${\alpha}$-adrenoceptor blocker, propranolol ; ${\beta}$-adrenoceptor blocker and the yohimbine；${\alpha}_2$-selective adrenoceptor blocker from physiograph. 1. The relaxation response induced by norepinephrine was the concentration of $10^{-6}$ M at first and maximum response was concentration of $10^{-4}$M. 2. The relaxation response induced by norepinephrine was not effected by the pretreatment with non-selective $\alpha$-adrenoceptor blocker, phentolanune ($10^{-6}$ M) but was completely blocked by the pretreatment with ${\beta}$-adrenoceptor blocker, propranolol($10^{-6}$ M). 3. The contractile response induced by electrical transmural nerve stimulation(20V, 10Hz, 0.5msec, 20sec ) was inhibited by the pretreatment with non-selective ${\alpha}$-adrenoceptor blocker, phentolamine($10^{-6}$ M) but was not inhibited and rather increased by the pretreatment ${\beta}$-adrenoceptor blocker, propranolol($10^{-6}$ M), and was not approximately effected by the pretreatment with ${\alpha}_2$-adrenoceptor blocker, yohimbine($10^{-6}$ M). These finding suggest that it was excitatory action by ${\alpha}_1$-adrenergic nerve and inhibitory action by ${\alpha}_2$-adrenergic, ${\beta}$-adrenergic nerve on uterine smooth muscle of the pig.

• 한국임상약학회지
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• 제33권2호
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• pp.86-96
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• 2023

Background: Using KIDS-KAERS database (KIDS-KD) from 2016 to 2020, the aim is to investigate signals of adverse events of alpha-adrenoceptor antagonists and to present adverse events that are not included in the precautions for use when marketing approval. Methods: This study was conducted by disproportionality analysis. Data mining analysis was performed to detect signals of alpha-adrenoceptor antagonists, such as terazosin, doxazosin, alfuzosin, silodosin, and tamsulosin. The signal was defined by three criteria as proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC). Detected signals were compared with product labeling and the European Medicines Agency-Important Medical Events list. Results: Out of the total number of 408,077 reports for adverse events, 6,750 cases were reported as adverse events of alpha-adrenoceptor antagonists. Dizziness, mouth dryness, hypotension postural, and oedema peripheral are identified as common adverse events of five alpha-adrenoceptor antagonists and are typically listed on drug labels. However, new signals were detected for pneumonia, chronic obstructive airway disease, eye diseases such as glaucoma and cataracts, fracture, and ileus of tamsulosin that were not previously listed on the drug labels in Korea. Conclusions: This study identified signals related to adverse drug reactions of alpha-adrenoceptor antagonists and presented serious adverse events, suggesting new adverse reactions to be aware of when using alpha-adrenoceptor antagonists.

• The Korean Journal of Physiology
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• 제27권1호
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• pp.27-35
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• 1993

Effects of the endothelium on the contractile responses to norepinephrine (NE) were investigated in isolated helical strips of the proximal and distal coronaries artery of pigs. The helical strips were immersed in Tris-buffered Tyrode's solution equilibrated with 100% $O_2$ at $35^{\circ}C$ and its isometric tension was measured. NE relaxed the strips precontracted with acetylcholine from both the proximal and distal coronary artery. NE-induced relaxation, which might be induced mainly by $\beta$-adrenoceptor function was dominant in the distal coronary arteries. NE-induced relaxation was converted to a contraction after $\beta$-adrenoceptor blockade with propranolol $(3{\times}10^{-6}M)$. ${\alpha}$-adrenoceptor-mediated contraction by NE was greater in the proximal coronary artery than the distal coronary artery. Quantitatively, ${\alpha}_1$-adrenoceptor mediated contraction by NE was greater than ${\alpha}_2$-adrenoceptor mediated contraction by NE in both arteries. NE-induced relaxation was decreased by rubbing of endothelium in both arteries. ${\alpha}_1-and\;{\alpha}_2$-adrenoceptor mediated contraction by NE were potentiated by rubbing of endothelium in both arteries. Pretreatment with methylene blue, an inhibitor of soluble guanylate cyclase, increased ${\alpha}_1-\;and\;{\alpha}_2$-adrenoceptor mediated contraction by NE in both arteries with endothelium. From the above results, we suggest that the effect of activation of $\alpha$-adrenoceptors by NE may be modulated by endothelium in the proximal and distal coronary arteries of pigs. This effect may be mediated via endothelium derived relaxing factor.

• 대한약리학회지
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• 제22권1호
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• pp.45-50
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• 1986

후신경구절제(OB) 흰쥐에 있어서 muricide의 발생은 중추성 ${\alpha}$-adrenoceptors의 기능항진과 밀접한 관계가 있다는 가설하에 다음 실험을 행하였다. Muricide를 일으키는 OB 흰쥐의 전뇌내 noradrenaline(NA)의 전환율은 대조군에 비하여 현저히 낮았으나 $_{{\alpha}_2}$-adrenoceptor 길항약물인 yohimbine이나 idazoxan 투여시 NA 전환은 muricide의 억제와 함께 현저히 증가되었다. OB흰쥐의 전뇌 피질막의 $[^3H]$ yohimbine에 대한 최대결합능(Bmax)은 대조군에 비하여 현저히 높았다. ${\alpha}$-Adrenoceptor 효능약물 및 길항약물에 대한 친화도는 아무런 변동이 없었다. 이상의 결과로 보아 OB흰쥐에서 야기되는 muricide는 중추성 ${{\alpha}_2}$-adrenoceptor의 기능 항진과 밀접한 관련이 있다고 사료되는 바이다.

• 대한약리학회지
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• 제31권1호
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• pp.39-51
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• 1995

갑상선 기능 항진증 심장에서의 ${\beta}-adrenoceptor$의 역할은 잘 알려져 있으나 ${\alpha}-adrenoceptor$에 대해서는 알려져 있지 않은 바, 저자 등은 갑상선 기능 항진증 기니픽 심장의 유두근에서 일반 미세 전극과 이온-선택적 미세 전극을 이용하여 세포내 $Na^+$과 $H^+$ 활성도에 대한 phenylephrine의 영향을 연구하였다. Phenylephrine ($10^{-5}$ 또는 $3{\times}10^{-5}M$)에 의한 ${\alpha}_1-adrenoceptor$ 자극은 다양한 활동전위의 변동, 수축기 막전위의 과분극 ($1.5{\pm}0.1mM$), 세포내 활성도 증가 ($0.4{\pm}0.15mM$), 현저한 수축력 증가 ($220{\pm}15%$) 그리고 세포내 pH의 증가 ($0.06{\pm}0.002\;unit$)를 일으켰고, 이와 같은 변동이 prazosin과 atenolol에 의해 차단되었다. 그래서 이들 효과가 ${\alpha}_1-adrenoceptor$를 경유함을 알 수 있었고, 역시, 세포내 $Na^+$ 활성도와 수축력 증가 효과가 $Na^{+}-H^{+}$ 교환기 억제제인 ethylisopropylamiloride로 차단됨으로 보아 ${\alpha}_1-adrenoceptor$ 자극은 $Na^{+}-H^{+}$ 교환기를 자극하여 세포내 $a^{i}_{Na}$와 pH를 증가시킴을 시사한다. 이는 ${\alpha}_1-adrenoceptor$ 자극에 의한 세포내 $Na^+$감소와 초기 수축력 감소 효과를 나타내는 정상 기니픽 심장과는 매우 다른 결과로 갑상선 기능 항진증 심장에서 ${\alpha}_1-adrenoceptor$는 매우 중요한 기능을 갖고 있음을 의미한다.

• 대한수의학회지
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• 제36권2호
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• pp.327-335
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• 1996

Recently in spite of the interest on the regulation of intracellular $Mg^{2+}$ by neurotransmitters or drugs, the magnesium ion($Mg^{2+}$) regulation by ${\alpha}_1$-adrenoceptor stimulation has not been studied in the heart yet. To elucidate the regulation of ${\alpha}_1$-adrenoceptor stimulation-induced $Mg^{2+}$ release and the effects of ${\alpha}_1$-adrenoceptor stimulation on pathophysiological conditions, in this study we have evaluated the effects of phenylephrine, PMA, $H_7$. staurosporine, verapamil and lidocaine on $Mg^{2+}$ release in perfused guinea pig heart. During preperfusion exogenous $Mg^{2+}$ was added to the medium to give 1.2mM 15min before starting to addition of drugs, and then the infusion of exogenous $Mg^{2+}$ was stopped. $Mg^{2+}$ in the perfusate leaving the heart was measured by atomic absorption spectrophotometry. $Mg^{2+}$ free solution produced an increase in heart rate and phenylephrine elicited $Mg^{2+}$ release from the heart. $Mg^{2+}$ release by phenylephrine was abolished by combined treatment with prazosin. By contrast, cardiac $Mg^{2+}$ uptake induced by a protein kinase C(PKC) activator, PMA was abolished by a selective PKC inhibitor, staurosporine. And the phenylephrine-induced $Mg^{2+}$ release was not affected by the PKC inhibitor, $H_7$. When verapamil or lidocaine was added to perfusing solution, $Mg^{2+}$ release was potentiated by phenylephrine from perfused guinea pig heart. These results suggest that ${\alpha}_1$-adrenoceptor stimulation caused $Mg^{2+}$ release and that PKC is not involved in ${\alpha}_1$-adrenoceptor mediated $Mg^{2+}$ release from perfused guinea pig heart. Under pathophysiological conditions, the $Mg^{2+}$ alteration by ${\alpha}_1$-adrenoceptor stimulation is considerable.

• 약학회지
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• 제30권3호
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• pp.157-162
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• 1986

$\alpha$-Adrenoceptor subtypes in the isolated rat aortic strips were examined by using agonists and antagonists which have varying selectivity for $\alpha_1$- and $\alpha_2$- adrenoceptors. Norepinephrine and phenylephrine produced a similar magnitude of maximum contractions. $pA_2$ values for prazosin and yohimbine were not significantly different using norepinephrine or phenylephrine as the agonist, suggesting a single population of alpha-adrenoceptor. Contractile responses produced by alpha-agonists were antagonized more effectively by prazosin (approximately 1000 fold) than by yohimbine.

• 대한약리학회지
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• 제22권1호
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• pp.24-33
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• 1986

본 연구에서는 개구리(Rana nigromaculata)의 피부에 있어서 전위차(PD), 단락전류(SCC) 및 total skin conductance(TSC)에 미치는 제종 adrenergic agonist 및 그 차단제의 영향을 관찰하여 개구리 피부에 adrenoceptors의 존재를 확인하고 Na 수송에 있어 그들의 역할을 구명코자 하였다. 1.Norepinephrine(NE, $6{\times}10^{-8}-6{\times}10^{-5}M$), phenylephrine($PE,5{\times}10^{-6}-5{\times}10^{-4}M$)의 PD 및 epinephrine(Epi, $5.5{\times}10^{-7}-5.5{\times}10^{-5}M$)의 PD 및 SCC 증가효과는 약물의 투여농도에 비례하였으며, Epi의 최대효과는 NE나 PE의 것보다 약하였다. 2. 이러한 PD 및 SCC의 증가효과는 alpha 1 adrenoceptor 차단체인 prazosin $2{\times}10^{-6}M$에 의해서 억제되었으며, 특히 Epi의 증가효과는 불가역성 alpha receptor 차단제인 phenoxybenzamine $3.3{\times}10^{-5}M$에 의하여 완전히 차단되며 대량의 Epi에 의해서는 PD 및 SCC의 감소를 초래하였다. 3. Beta adrenoceptor agonist인 isoproterenol$(5{\times}10^{-7}-5{\times}10^{-6}M)$에 의해 농도증가에 비례한 PD 및 SCC의 감소가 일어났으며, 이는 선택적 bete receptor 차단제인 propranolol $4{\times}10^{-6}M$에 의해 차단되었다. 또한 Epi의 PD 및 SCC 증가효과는 propranolol $4{\times}10M$에 의하여 강화됨을 볼 수 있었다. 4. Alpha 2 adrenoceptor agonist인 clonidine 및 guanabenz도 PD 및 SCC의 증가를 가져왔으며 이러한 효과는 alpha 2 receptor 차단제인 yohimbine에서 보다 Alpha 1 receptor 차단제인 prazosin에 의해 더 잘 억제되었다. 이상 실험의 결과 개구리 복부피부에도 포유동물에서와 같이 adrenergic alpha 및 beta receptor가 존재하며 alpha receptor는 PD 및 SCC의 증가를, beta receptor는 PD 및 SCC의 감소를 매개하여, 개구리 피부의 Na 수송에 있어 adrenergic system이 중요한 조절작용을 하고 있음을 알 수 있었다. 그러나 여기에 관여하는 alpha receptor는 다른 포유류에서와 같이 alpha 1 및 alpha 2 adrenoceptor로 구분할 수는 없었다.

• 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.