신우황청심원액의 심혈관계에 관한 약효연구

조태순,이선미,김낙두,허인회,안형수,권광일,박석기,심상호,신대희,박대규 충남대학교 약학대학 의약품개발연구소 1997 藥學論文集 Vol.13 No.-

In order to investigate the pharmacological properties of New Woohwangchungsimwon Liquid (NCL), efects of Woohwangchungsimwon Liquid (CL) and NCL were compared. In isolated rat aorta, NCL and CL showed the relaxation of blood vessels in maximum contractile response to phenylephrine (10^6M) without regard to intact endothelium or denuded rings of the rat aorta. Furthemore, the presences of the inhibitor of NO synthase and guanylate cyclase did not affect the relaxation of NCL and CL. NCL and CL inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dosedependent manner. In conscious spontaneously hypertensive rats (SHRs), NCL and CL significantly decreased heart rate. NCL and CL, at high doses, had a negative inotropic effect that was a decrease of LVDP and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In excised guinea-pig papillary muscle, NCL and CL had no efects on parameters of action potential at low doses, whereas inhibited the cardiac contractility at high doses. These results suggested that NCL and CL have weak cardiovascular effects with relaxation of blood vessels and decrease of heart rate, and that this effect is no significant differences between two preparations.

신원방우황청심원의 심혈관계에 관한 약효

조태순,이선미,김낙두,허인회,안형수,권광일,박석기,심상호,신대희,박대규 성균관대학교 약학연구소 1999 成均藥硏論文集 Vol.11 No.-

Abstract-In order to investigate the phamacological properties of New Wonbang Woohwangchungsimwon Pill (NSCH), effects of Wonbang Woohwangchungsimwon Pill (SCH) and NSCH were compared using various experimental models. In rat aorta, NSCH and SCH made the relaxation of blood vessels in maximum contractile response to phenylephrine (10^-6 M) regardless to endothelium containing or denuded rings of the rat aorta. Furthermore, the presence of the inhibitors of NO synthase and guanylate cyclase did not aftect significantly the relaxing effects of NSCH and SCH, NSCH and SCH inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs). NSCH and SCH decreased significantly heart rate. These, at high doses, had a negative inotropic effect that was a decrease of left ventricular developed pressure and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In guinea-pig papillary muscle, these had no effects on parameters of action potential such as action potential amplitude (APA). V_max and resting membrane potential (RMP) at low doses, whereas inhibited the cardiac contractility at high doses. Furthermore, these had a significant inhibitory effects on palpitation of the heart in normotensive rats and SHRs. These results suggest that NSCH and SCH have weak cardiovascular effects, and that there is no significant differences between cardiovascular effects of two preparations.

신우황청심원의 심혈관계에 대한 약효

조태순(Tai Soon Cho),이선미(Sun Mee Lee),허인회(In Hoi Huh),안형수(Hyung Soo Ann),권광일(Kwang Il Kwon),박석기(Seok Ki Park),심상호(Sang Ho Shim),신대희(Dae Hee Shin),박대규(Dai Kyu Park),김낙두(Nak Doo Kim) 대한약학회 1997 약학회지 Vol.41 No.6

In order to investigate the pharmacological properties of New Woohwangehungsimwon Pill (NWCH). Effects of Woohwangehungsimwon Pill (WCH) and NWCH were compared using various experimental models. In isolated rat aorta, NWCH and WCH showed the relaxation of blood vessels in maximum contractile response to phenylephrine (10-6M) without regard to endothelium containing or denuded rings of the rat aorta. Furthermore, the presence of the inhibitors of NO synthase and guanylate cyclase did not affect significantly the relaxative effects of NWCH and WCH. NWCH and WCH inhibited the vascular contractions induced by acethylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats(SHRs), NWCH and WCH decreased significantly heart rate. These, at high doses, had a negative inotropic effect that was a decrease of LVDP and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In excised guinea-pig papillary muscle, these had no effects on parameters of action potential at low doses, whereas inhibited the cardiac, contractility at high doses. Furthermore, these had a significant inhibitory effects on heart acceleration in normotensive rats and SHRs. These results suggested that NWCH and WCH have weak cardiovascular effects, and that there is no significant differences between two preparations.

신원방우황청심원의 심혈관계에 관한 약효

조태순,이선미,김낙두,허인회,안형수,권광일,박석기,김상호,신대희 대한약학회 1999 약학회지 Vol.43 No.2

In order to investigate the pharmacologic properties of New Wonbang Woohwangchungsimwon Pill(NSCH), effects of Wonbang Woohwangchungsimwon Pill (SCH) and NSCH were compared using various experimental models. In rat aorta, NSCH and SCH made the relaxation of blood vessels in maximum contractile response to phenylephrine (10-6 M) regardless to endothelium containing or denuded rings of the rat aorta. Furthermore, the presence of the inhibitors of NO synthase and guanylate cyclase did not affect significantly the relaxing effects of NSCH and SCH. NSCH and SCH inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NSCH and SCH decreased significantly heart rate. These, at high doses, had a negative inotropic effects that was a decrease of left ventricular developed pressure and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In guinea-pig papillary muscle, these had no effects on parameters of action potential such as action potential amplitude (APA), $V_{max}$ and resting membrane potential (RMP) at low doses, whereas inhibitory the cardiac contractility at high doses. Furthermore, these had a significant inhibitory effects on palpitation of the heart in normotensive rats and SHRs. These had a significant inhibitory effects on palpitation of the heart in normotensive rats and SHRs. These results suggest that NSCH and SCH have weak cardiovascular effects, and that there is no significant differences between cardiovascular effects of two preparations.

신원방우황청심원액의 심혈관계에 관한 약효

조태순,이선미,김낙두,허인회,안형수,권광일,박석기,심상호,신대희,박대규 충남대학교 약학대학 의약품개발연구소 1999 藥學論文集 Vol.15 No.-

In order to investigate the pharmacological properties of New Wonbang Woohwangchungsimwon Liquid (NSCL), effects of Wonbang Woohwangchungsimwon Liquid (SCL) and NSCL were compared. In isolated rat aorta, NSCL and SCL showed the relaxation of blood vessels in maximum contractile response to phenylephrine (10^-6M) regardless to intact endothelium or denuded rings of the rat aorta. Furthermore, the presences of the inhibitor of NO synthase and guanylate cyclase did not affect the relaxing effect of NSCL and SCL. NSCL and SCL inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NSCL and SCL significantly decreased heart rate. NSCL and SCL, at high doses, had a negative inotropic effect that was a decrease of left ventricular developed pressure and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In excised guinea-pig papillary muscle, NSCL and SCL had no effects on parameters of action potential such as resting membrane potential, action potential amplitude, APD_90 and V_max at low doses, whereas inhibited the cardiac contractility at high doses. These results suggested that NSCL and SCL have weak cardiovascular effects with relaxation of blood vessels and decrease of heart rate, and that this effect is no significant differences between cardiovascular effects of two preparations.

신원방우황청심원액의 심혈관계에 관한 약효

조태순,이선미,김낙두,허인회,안형수,권광일,박석기,심상호,신대희,박대규 성균관대학교 약학연구소 1999 成均藥硏論文集 Vol.11 No.-

Abstract-In order to investigate the pharmacological properties of New Wonbang Woohwangchungsimwon Liquid (NSCL), effects of Wonbang Woohwangchungsimwon Liquid (SCL) and NSCL were compared. In isolated rat aorta, NSCL and SCL showed the relaxation of blood vessels in maximum contractile response to phenylephrine (10^-6 M) regardless to intact endothelium or denuded rings of the rat aorta. Furthermore, the presences of the inhibitor of NO synthase and guanylate cyclase did not affect the relaxing effect of NSCL and SCL. NSCL and SCL inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NSCL and SCL significantly decreased heart rate. NSCL and SCL, at high doses, had a negative inotropic effect that was a decrease of left ventricular developed pressure and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In excised guinea-pig papillary muscle, NSCL and SCL had no effects on parameters of action potential such as resting membrane potential, action potential amplitude, APD_90 and V_max at low doses, whereas inhibited the cardiac contractility at high doses. These results suggested that NSCL and SCL have weak cardiovascular effects with relaxation of blood vessels and decrease of heart rate, and that this effect is no significant differences between cardiovascular effects of two preparations.

Synthesis of Higenamine and its Cardiovascular Effects in Rabbit: Evidence for ${\beta}-Adrenoceptor$ agonist

장기철,임정규,박찬웅,Chang, Ki-Churl,Lim, Jung-Kyoo,Park, Chan-Woong The Korean Society of Pharmacology 1986 대한약리학잡지 Vol.22 No.2

최근에 미나라아제비과 (Ranunculaceae)에 속하는 부자(Aconiti tuber)로부터 강심작용을 나타내는 성분을 분리하여 Higenamine이라 명명하였고 그 작용기전을 밝히려는 시도가 활발히 진행되고 있다. 그러나 생약제로 부터 얻을 수 있는 Higenamine은 극히 미량이고 그 과정 또한 복잡하다. 따라서 본 연구에서는 유효성분을 대량 얻기 위한 방법으로서 전합성(total Synthesis)을 시도하였으며 IR, UV, NMR 및 elemental 분석등을 통하여 합성된 물질을 확인하였으며 가토에 대하여 in vivo에서 혈압, 심박동수, 호흡 및 말초저항에 미치는 영향과 아울러 in vitro에서 심근수축 증강작용(positive inotropic action) 및 심박속도 증강작용(positivechronotropic action)을 관찰 분석하여 다음과 같은 결론을 얻었다. 1) Higenamine은 $1-10\;{\mu}g/kg/min$ 정맥주사시 수축기 및 이완기혈압 모두를 용량 의존적으로 하강시켰고 후자가 전자보다 더욱 현저하였으며 호흡은 촉진되었고 말초 혈류량은 증가되었으나 심박동수는 영향이 없었다. 2) 혈압에 대한 Higenamine의 작용은 propranolol 전처치에 의하여 억제되었다. 3) Higenamine의 catechol핵과 커다란 아미노기는 베타 수용체기 대하여 전자는 활성을 후자는 친화력과 관계있을 것으로 추정하였다. 이상의 결과 Higenamine은 adrenergic ${\beta}$-수용체에 작용하여 그 작용을 발휘하는 것으로 사료 되었다. Higenamine, dl-1-( 4-hydroxybenzyl)-6, 7-dihydroxy-1 ,2, 3 ,4-tetrahydroisoquinoline has been synthesized and evaluated for hemodynamic actions using rabbits under pentobarbital anesthesia. Concentration-related fall of mean blood pressure was observed, where diastolic blood presure was significantly lowered at 10 ug/kg/min or above (p<.05), while the systolic blood pressure was slightly increased or unaffected, thereby, causing increment of pulse pressure. No significant change was occured in heart rate, however, carotid artery blood flow was significantly (p<.05) increased. These actions were inhibited with pretreatment of 0.3 mg/kg of propranolol, beta-adrenoceptor antagonist, 5 minutes before infusion of higenamine indicating that higenamine compete with propranolol for the so-called beta adrenergic receptor. As comparison, the same procedure was applied to isoproterenol as well, where typical antagonism of propranolol against isoproterenol was shown. From these findings the vasodilating and diastolic blood pressure lowing effects could be explained in terms of cardiac beta stimulating action, however, dopamine receptor activation could not be excluded because no significant changes observed in chronotropism.

Tetrahydroisoquinoline Alkaloids가 쥐의 동맥과 뇌균등질의 α-Adrenoceptors에 미치는 영향

이현석,백선하,황수현,박인성,김은상,정진명,한종우,장기철,장기철 대한신경외과학회 1999 Journal of Korean neurosurgical society Vol.28 No.1

Comparison of Inodilator Effect of Higenamine, YS49, YS51, Tetrahydroisoquinoline Analogs, and Dobutamine in the Rat

Won-Seog Chong,Young-Soo Lee,Young-Jin Kang,Duck-Hyung Lee,Jae-Chun Ryu,Hye Sook Yun-Choi,Ki-Churl Chang 대한생리학회-대한약리학회 1998 The Korean Journal of Physiology & Pharmacology Vol.2 No.3

<P> Tetrahydroisoquinoline (THI) alkaloids can be considered as cyclized derivatives of simple phenylethylamines. Many of them, especially with 6,7-disubstitution, demonstrate a relatively high affinity for catecholamines. Present study examines the pharmacological action of limited series of THI, using rats isolated atria and aorta. In addition, a [<SUP>3</SUP>H] prazosin displacement binding study with THI compounds was performed, using rat brain homogenates to investigate whether these probes have ㄁-adrenoceptor affinity. We also compared the vascular relaxation potency of these probes with dobutamine. YS 49, YS 51, higenamine and dobutamine, concentration-dependently, relaxed endothelium-denuded rat thoracic aorta precontracted with phenylephrine (PE, 0.1 ㄍM) in which pEC<SUB>50</SUB> were 5.56⁑0.32 and 5.55⁑0.21, 5.99⁑1.16 and 5.57⁑0.34, respectively. These probes except higenamine also relaxed KCl (65.4 mM)-contracted aorta. In isolated rat atria, all THIs and dobutamine increased heart rate and contractile force. In the presence of propranolol, the concentration response curves of YS 49 and YS 51 shifted to the right and resulted in pA<SUB>2</SUB> values of 8.07⁑0.84 and 7.93⁑0.11, respectively. The slope of each compound was not deviated from unity, indicating that these chemicals are highly competitive at the cardiac ㄂-adrenoceptors. YS 49, YS 51, and higenamine showed ㄁-adrenoceptor affinity in rat brain, in which the dissociation constant (K<SUB>i</SUB>) was 2.75, 2.81, and 1.02 ㄍM, respectively. It is concluded, therefore, that THI alkaloids have weak affinity to ㄁<SUB>1</SUB>-adrenoceptors in rat aorta and brain, respectively, while these probes show relatively high affinity for cardiac ㄂-adrenoceptors. Thus, these chemicals may be useful in the treatment of congestive heart failure.