• 대한약리학회지
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• 제28권1호
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• pp.75-79
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• 1992

Higenamine은 부자의 활성 성분의 하나로서 아드레나린성 beta-수용체를 통하여 강심효과를 나타내는 것으로 알려졌다. 본 연구는 norepinephrine 또는 potassium에 의한 토끼 페동맥의 수축에 미치는 Higenamine의 영향을 관찰한 것이다. 1. Norepinephrine으로 수축을 이르킨 폐동맥편은 higenamine의 전처치 또는 후처치로 용량의존적으로 이완되었다. 이같은 higenamine의 효과는 propranolol 전처치로 억제되었다. Higenamine의 propranolol에 대한 $pA_2$ 값은 8.25였다. 2. Higenamine의 페동맥편에 대한 효과는 phentolamine 전처치로 억제되지 않았다. 3. Isoproterenol도 norepinephrine에 의한 페동맥편 수축을 이완시켰으며 효력은 higenamine 보다 10배 켰다. 그러나 고농도$(3.3{\times}10^{-6})$의 isoproterenol은 내인성 활성을 보였다. 4. Higenamine과 isoproterenol은 potassium으로 유도된 페동맥편 수축에 대하여 이완효과를 나타내지 않았다. 이상의 결과로 미루어 higenamine은 혈관평활근에 대하여도 아드레나린성 beta-수용체를 통하여 이완효과를 나타낼 것으로 생각된다.

• Archives of Pharmacal Research
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• 제16권3호
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• pp.213-218
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• 1993

($\pm$)-Higenamine is known as a cardiotonic principle of aconite root (root of Aconitum spp., Ranunculaceae). A simple and sensitive detection method for higenamine was developed by using gas chromatography-mass spectrometry (GC/MS). The recovery of higenamine after extraction and concentration with XAD-2 resin column was around 95% from rat biological fluids such as bile, plasma and urine. The limits of detection of higenamine in these biological fluids were approximately 0.1 ng/ml each. It has well been suggested that tetrahydroisoquinolines possessing catechol moiety such as higenamine should be subjected to the catechol-O-methyl transferase (COMT) activity in vivo. We detected two major peaks of presumed metabolites of higenamine in the total ion chromatogram obtained from the rat urine sample after the oral adminstration of ($\pm$)-higenamine. The scan mass spectrum of one of the metabolties coincided with those obtained from coclaurine $(C_6$-O-methyl higenamine) and those of the other metabolite are suggestive of isococlaurine $(C_7$-O-methyl higenamine).

• 대한약리학회지
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• 제19권2호
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• pp.9-16
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• 1983

현재 사용되고 있는 강심제로는 디지탈리스 배당체가 유일한 약물이지란 그 안전역이 대단히 좁아서 보다 안전한 강심제의 개발이 요구되고 있다. 최근 강심작용이 현저할 뿐 아니라 안전역이 비교적 넓을 것으로 인정되는 higenamine이 개발되어 그 작용기전을 밝히려는 시도가 많이 있었다. 본 연구에서는 higenamine의 강심작용 기전을 규명하기 위한 연구의 일환으로 수축빈도-수축력 상관관계(interval-strength relationship)에 있어서 1) Rested-state수축력 2) Positive inotropic effect of activation(PIEA) 3) Negative inotropic effect of activation(NIEA)에 대한 higenamine의 영향을 $Ca^{++}$및 epinephrine과 비교 분석하였다. 실험결과 칼슘은 PIEA를 증가시키기 보다는 오히려 NIEA의 소멸을 촉진함으로써 강심작용을 나타내며 epinephrine 및 higenamine은 PIEA를 증가시키고 NIEA에는 거의 영향을 미치지 않았다.

• 약학회지
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• 제38권2호
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• pp.191-196
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• 1994

Higenamine is a tetrahydroisoquinoline alkaloid which was isolated as a cardiotonic principle from Aconiti tuber. 1.v. injection of higenamine was reported to increase the cardiac output and heart rate and to decrease the blood pressure and the systemic vascular resistance presumably by stimulating the adrenergic ${\beta}-receptors$. The anti-platelet and anti-thrombotic effects of higenamine were investigated in this paper. Higenamine(0.5 mg/ml) showed mild inhibitory effect against collagen induced platelet aggregation in vitro and the inhibito교 effect was increased with the pre-incubation$(5{\sim}30\;min)$ of platelet rich plasma(PRP) with higenamine. With the 30 min incubation, the platelet aggregation was almost completely inhibited. And the oral administration of higenamine$(50{\sim}200\;mg/kg)$ enhanced the survival in the mouse model of thrombosis and that of endotoxic shock. The anti-thrombotic and anti-septic effects of higenamine thus appear to be due to the ${\beta}-agonistic$ and the anti-platelet effects of this compound.

• Natural Product Sciences
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• 제6권1호
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• pp.20-24
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• 2000

The enantiomers of higenamine were directly separated by high performance liquid chromatography using a chiral stationary phase and detected by UV. The R- and S-isomers of higenamine were eluted at the retention time of 22 min and 27 min, respectively. Higenamine was determined to be present as R-(+)-enantiomer not only in the embryo of Nelumbo nucifera, from which the separation of R-(+)-higenamine was reported, but also in various Aconite roots, from which higenamine was separated as optically inert racemic mixtures.

• Plant Resources
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• 제6권1호
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• pp.81-88
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• 2003

Higenamine [1-(4-hydroxy-6, 7-dihydroxy-l, 2, 3, 4-tetrahydroisoquinoline) is a cardiotonic constituent of Aconiti tuber, one of the most widely prescribed oriental medicines. S-(-)higenamine was reported to have a stronger cardiotonic activity than R-(+)-higenamine and known as a central intermediate in the biosynthesis of various benzyl isoquionoline alkaloids in plants. The separation of higenamine enantiomers has been accomplished with capillary electrophoresis using cyclodextrins (CDs) as chiral selectors. Good resolution of this enantiomers was obtained using a 50 mM sodium phosphate buffer containing hydroxypropyl $\beta$-CDs using 27 cm fused silica capillary (50${\mu}{\textrm}{m}$ i.d., 20 cm to detector) at 25 $^{\circ}C$. With the electric field of 340 V/cm, the separation time of higenamine enantiomers was less than 6 min. Under this optimum conditions, the relative standard deviations of migration time and peak area were less than 1.6% and 3.2%. A 512-channel diode array detector was confirmed for the higenamine. The detection limits (S/N = 3) of these enantiomers are $1.5mutextrm{m}$/mL. We confirmed the chiral form of higenamine in medicinal plants.

• The Korean Journal of Physiology and Pharmacology
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• 제1권3호
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• pp.297-302
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• 1997

Higenamine was widely used as traditional remedy for the treatment of rhumatoid arthritis. Nitric oxide(NO) may be a critical mediator in this inflammatory disease. Synovial tissue from humans with inflammatory arthritis expresses NOS2(iNOS) mRNA and protein, and generates NO in vitro. We therefore, investigated the effect of higenamine on the induction of nitric oxide synthase(NOS) promoted by lipopolysaccharide(LPS). Prophylactic application of higenamine selectively prevented LPS-primed initiation of L-arginine-induced relaxation and restored rhenylephrine(PE)-induced contraction in rat aorta. LPS-stimulated nitrite production in the incubation medium was reduced by higenamine. Furthermore, RT-PCR and Northern analysis indicated that higenamine reduced iNOS expression primed by LPS in rat aorta. These results suggest that higenamine prevents LPS-promoted induction of NOS in vascular smooth muscle.

• Natural Product Sciences
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• 제5권4호
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• pp.181-185
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• 1999

Higenamine is a cardiotonic constituent of Aconite root, one of the most important oriental traditional medicine. Since Aconite root contains toxic aconitine alkaloids, variously processed roots have been often used. Much works have been done with the chemical significances concerning with the toxic aconitine alkaloids during the processing periods. However, effects of processing on higenamine have not yet been previously studied. In this paper, the extract pattern and the amounts of higenamine extracted with water from unprocessed and processed Aconite roots were compared. R-(+)-isomer was the only higenamine enantiomer detected although racemic higenamine was reported to be separated from Aconitum spp. Sonication for 1 hour resulted in higher higenamine extraction $(12.3\;{\mu}g/g)$ than boiling water extraction for 3 hours $(6.7\;{\mu}g/g)$ of unprocessed Aconite root. Extraction of not only higenamine but also most of the other components of unprocessed Aconite roots were reduced with boiling in water. Similarly, reduced extraction was observed with extracts of all three processed Aconite roots (Kyung-Po-Aconite root, Dang-Po-Aconite root and Huk-Peon-Aconite root) by either sonicated extraction or boiling water extraction.

• 생약학회지
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• 제29권2호
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• pp.129-135
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• 1998

Higenamine is known as a cardiotonic principle of Aconiti tuber. The analytical procedures were established for the detection of higenamine in plants. The amounts of higenamine in several Aconiti tubers and the embryo of Nelumbo nucifera, another plant species known to contain higenamine, were determined. The $H_2O$ soluble fraction prepared from MeOH extract was first treated with AD-2 resin and then applied to either HPLC or GC/MSD systems. With HPLC, $6.4{\sim}19.2\;{\mu}g/g$ of higenamine were detected from various Aconiti tubers and $182.3\;{\mu}g/g$ of higenamine from the embryo of Nelumbo nucifera. The results obtained with GC/MSD also provided comparable data with those obtained with HPLC.

• 대한수의학회지
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• 제27권1호
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• pp.35-40
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• 1987

Higenamine, a benzyltetrahydroisopuinoline analog isolated from aconite tuber, has potent isotropic action. Recent studies suggest it may have beta receptor agonistic property in that its inotropic action is blocked by propranolol in isolated rabbit heart. However, no study has been carried out on other organs than heart. Higenamine is expected to have pharmacological actions on smooth muscle on the ground that it has catecholamine moiety and tetrahydrosioquinoline nucleus in its chemical structure, both of which are well known to have smooth muscle relaxation effects. Therefore present study was aimed at determining whether higenamine has bronchodilating effect in isolated guinea pig trachea smooth muscle rich in adrenergic beta receptor and if any, it has agonistic effect on beta receptor. The results were summarized as follows : 1. Higenamine had remarkable bronchodilating effect in guinea pig tracheal smooth muscle in a dose-dependent manner. 2. Bronchodilator effect of higenamine in isolated guinea pig tracheal smooth muscle was blocked competitively by propranolol. The $pD_2$ value of higenamine in isolated guinea pig tracheal smooth muscle was 5.65 and the $pA_2$ value of propranolol against higenamine in the same preparation was 7.97.