• Proceedings of the PSK Conference
• /
• 2003.10b
• /
• pp.245.2-245.2
• /
• 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
• /
• v.25 no.6
• /
• pp.525-532
• /
• 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.

• The Korean Journal of Pharmacology
• /
• v.21 no.2
• /
• pp.90-98
• /
• 1985

1) In the study of the forced-swimming test in mice (FSM), the duration of immobility posture was dose-dependently shortened by ${\alpha}_2$-agonists, clonidine and guanabenz. BH-T 933 and oxymetazoline also decreased it . Xylazine rather increased the immobility duration at low dose. 2) ${\alpha}_1$-Agonists, cirazoline, amidephrine and methoxamine, however, showed inconsistent effect on the immobility duration (ID). 3) The decrease in ID by clonidine and guanabenz was antagonized by pretreatment with yohimbine, idazoxan and phentolamine (${\alpha}_2$antagonist), but not by prazosin and corynanthine (${\alpha}_1$-antagonist) .4) The ID in the FSM was shortened dose-dependently by d-amphetamine, and it was also antagonized by yohimbine, but not by prazosin. 5) In the mice pretreated with either ${\alpha}$-methyl-p-tyrosine or reserpine, or with combination of both, the decrease in ID was still evoked by clonidine. 6) When the mice were chronically treated with antidepressants (desipramine and imipramine), or with electroconvulsive shock, clonidine still decreased the ID as it did in the control. 7) These results provided the evidences to hypothesize that the change of the ID in the FSM is closely related with the postsynaptie ${\alpha}_2$-adrenoceptor located on the central noradrenergic neuron body. Furthermore, it is assumed that this escape-directed behavior enhanced by ${\alpha}_2$-adrenoceptor agonist may be the result in some analogy with the incentive of drives which are directed toward the self-preservation.

• The Korean Journal of Pharmacology
• /
• v.20 no.2
• /
• pp.7-14
• /
• 1984

In pithed rats, rising in diastolic blood pressure by clonidine, when intravenously injected, is expressed as the postsynaptic action, and inhibitory action on electrical stimulation-induced tachycardia by clonidine is expressed as the presynaptic inhibitory action. In this study it was aimed to observe the inhibitory effect of imipramine caused by a single and chronic administration on both postsynaptic and presynaptic action of clonidine in pithed rats, and discussed in relation with the mechanism of antidepressant action of imipramine. 1) A rise of diastolic blood pressure by clonidine was not antagonized by prazosin, but by both phentolamine and piperoxan. 2) The inhibition by clonidine of tachycardia which was induced by electrical stimulation was also antagonized by phentolamine and piperoxan, but not by prazosin. 3) The increase in diastolic blood pressure in response to clonidine was inhibited by both a single or chronic administration with imipramine (20 mg/kg). It was more pronounced in the latter. 4) The inhibitory action of clonidine on the tachycardia was markedly inhibited by both types of administration with imipramine, between which there showed little difference. It is concluded that the presynaptic ${\alpha}_2-adrenoceptor$ is rather sensitively affected by a single administration with imipramine, and a long-term imipramine treatment may inhibit both pre- and postsynaptic ${\alpha}_2-adrenoceptors$, simultaneously. Furthermore, it was seemed unlikely that these results provide the evidence :to support the fact that the subsensitivity of presynaptic ${\alpha}_2-adrenoceptor$ may be the mechanism of action of tricyclic antidepressant.

• Korean Journal of Pharmacognosy
• /
• v.21 no.2
• /
• pp.173-178
• /
• 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
• /
• v.2 no.1
• /
• pp.55-62
• /
• 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
• /
• v.23 no.6
• /
• pp.1107-1117
• /
• 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
• /
• v.2 no.6
• /
• pp.753-761
• /
• 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
• /
• v.28 no.1
• /
• pp.37-44
• /
• 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
• /
• v.29 no.2
• /
• pp.203-216
• /
• 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.