1.Research progress of Pictet-Spenglerases.
Yunchang XIE ; Qi CHEN ; Shaofei ZHANG ; Chuanpu SHEN
Chinese Journal of Biotechnology 2020;36(10):2001-2016
Pictet-Spenglerases (P-Sases) catalyze the Pictet-Spengler (P-S) reactions and exhibit high stereoselectivity and regioselectivity under mild conditions. The typical P-S reaction refers to the condensation and recyclization of β-arylethylamine with aldehyde or ketone under acidic conditions to form tetrahydroisoquinoline and β-carboline alkaloid derivatives. The related enzymatic products of P-Sases are the backbones of various bioactive compounds, including clinical drugs: morphine, noscapine, quinine, berberine, ajmaline, morphine. Furthermore, the activity of P-Sases in stereoselective and regioselective catalysis is also valuable for chemoenzymatic synthesis. Therefore, this review summarizes the research progress in the discovery, functional identification, biological characteristics and catalytic applications of P-Sases, which provide the useful theoretical reference in future P-Sases research and development.
Alkaloids/chemistry*
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Catalysis
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Enzymes/metabolism*
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Research/trends*
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Tetrahydroisoquinolines/chemistry*
2.Design, synthesis and anti-platelet aggregation activities of ligustrazine-tetrahydroisoquinoline derivatives.
Di XIE ; En-li ZHANG ; Jia-ming LI ; Jie WANG ; Guang-wei HE
Acta Pharmaceutica Sinica 2015;50(3):326-331
Abstract: Fifteen novel ligustrazine-tetrahydroisoquinoline derivatives were designed and synthesized according to the association principle of pharmaceutical chemistry. The structures were identified by IR, NMR and ESI-MS. The inhibitory activities of platelet aggregation induced by ADP and AA have been measured by Bron method. Preliminary pharmacological results showed that compounds 7g, 7h and 7n had potent inhibitory activity against platelet aggregation induced by AA, and the compound 7o showed significant inhibitory activity against platelet aggregation induced by ADP.
Drug Design
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Platelet Aggregation
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drug effects
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Platelet Aggregation Inhibitors
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chemical synthesis
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chemistry
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Pyrazines
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chemical synthesis
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chemistry
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Tetrahydroisoquinolines
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chemical synthesis
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chemistry
3.Synthesis of isothioureas derived from tetrahydroisoquinoline and NOS inhibitory activity.
Acta Pharmaceutica Sinica 2005;40(11):988-993
AIMTo get some novel potent compounds with NOS inhibitory activity, a series of new compounds of isothioureas derived from 1,2,3,4-tetrahydroisoquinoline were synthesized.
METHODS1,2, 3,4-Tetrahydroisoquinol-2-yl was introduced into the structure of isothioureas, the NOS inhibitory activity of the new compounds synthesized were measured.
RESULTS AND CONCLUSIONTwenty-two isothiourea derivatives of [alkyl(or aryl) imino] (1,2,3,4-tetrahydroisoquinol-2-yl) methyl alkyl thioethers (I) and S-alkyl-1-phenyl-3-[4-(1,2,3,4-tetrahydroisoquinol-2-yl) methane] phenyl isothioureas (II) were synthesized from thioureas by S-alkylation with alkyl halides, and their structures were identified by IR, 1H NMR, MS and elemental analysis. The preliminary biological test showed that the part of type I (1-9 and 1-13) had higher NOS inhibitory activity than that the control aminoguanidine (AG), but the type II had weak ability to inhibit NOS.
Molecular Structure ; Nitric Oxide Synthase ; antagonists & inhibitors ; metabolism ; Stereoisomerism ; Tetrahydroisoquinolines ; chemistry ; Thiourea ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology
4.Photo-degradation products of 1-1-(6-methoxy-2-naphthyl)ethyl-2-(4-nitrobenzyl)-6,7-dimethoxyl-1,2,3,4-tetrahydroisoquinoline hydrobromide.
Hong JIANG ; Min SONG ; Tai-jun HANG ; Zheng-xing ZHANG
Acta Pharmaceutica Sinica 2007;42(10):1078-1081
To study the photo-degradation products of 1-[1-(6-methoxy-2-naphthyl) ethyl]-2-(4-nitrobenzyl)-6,7-dimethoxyl-1,2,3,4-tetrahydroisoquinoline hydrobromide (code designation: P91024). The chemical structures of the major photo-degradation products of P91024 were identified by HPLC-MS and spectroscopic methods, and their reference substances were also synthesized for confirmation. The three major photo-degradation products were identified to be N-(4-nitrobenzyl)-6,7-dimethoxyl-3, 4-dihydroisoquinoline bromide, 1-[1-(6-methoxyl-2-naphthyl) ethyl]-6, 7-dimethoxyl-1, 2, 3, 4-tetrahydroisoquinoline and 2-isopropyl-6-methoxyl-naphthalene, respectively.
Chromatography, High Pressure Liquid
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methods
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Fibrinolytic Agents
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chemistry
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Molecular Structure
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Photolysis
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Quality Control
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Spectrometry, Mass, Electrospray Ionization
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methods
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Tandem Mass Spectrometry
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methods
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Tetrahydroisoquinolines
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chemistry
5.Design, synthesis, and PPARalpha/gamma agonistic activity of novel tetrahydroisoquinoline derivatives.
Ran YU ; Yan-Li ZHOU ; Yi HUAN ; Quan LIU ; Zhu-Fang SHEN ; Zhan-Zhu LIU
Acta Pharmaceutica Sinica 2011;46(3):311-316
A series of tetrahydroisoquinoline derivatives were prepared and their peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonistic activities were evaluated to obtain more potent PPAR agonist. All of them were new compounds, and their structures were confirmed by 1H NMR and HR-MS. Three compounds exhibited higher agonistic activities of PPARgamma than that of the comparison, six compounds exhibited higher agonistic activities of PPARalpha than that of the comparison, and compound 8a was discovered as a highly potent PPARalpha/gamma agonist that is much more active than that of WY14643 and rosiglitazone. The development of potent PPAR agonists may offer a new choice for the treatment of diabetes.
Drug Design
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HEK293 Cells
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Humans
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Hypoglycemic Agents
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chemical synthesis
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chemistry
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pharmacology
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PPAR alpha
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agonists
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metabolism
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PPAR gamma
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agonists
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metabolism
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Structure-Activity Relationship
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Tetrahydroisoquinolines
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chemical synthesis
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chemistry
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pharmacology
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Transfection
6.Bioactivity diversity and functional mechanism of tetrahydroisoquinoline alkaloids.
Ce-Jia LIU ; Dian-Yu LIU ; Lan XIANG
Acta Pharmaceutica Sinica 2010;45(1):9-16
Tetrahydroisoquinoline alkaloids distributed widely in the nature and some have a broad application in clinic. More attention has been paid in recent years on this type of alkaloid, owing to the diverse range of biological activities exhibited by these alkaloids and the discovery of new functional mechanisms and molecular targets underlying these activities. This article summarized the recent advances in the biological activities and functional mechanism of tetrahydroisoquinoline, which included the activities such as antitumor, antibiotic, antivirus, anti-inflammatory, anticoagulation, bronchodilation, and the action on central nervous system, with the purpose of providing some ideas in the study of biological activity of this type of alkaloid and in the search for lead-compound and rational drug design.
Animals
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Anti-Inflammatory Agents
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pharmacology
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Anticonvulsants
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pharmacology
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Antifungal Agents
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pharmacology
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Antineoplastic Agents
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pharmacology
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Antiviral Agents
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pharmacology
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Bronchodilator Agents
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pharmacology
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Central Nervous System Agents
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pharmacology
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Fibrinolytic Agents
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pharmacology
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Humans
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Neuroprotective Agents
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pharmacology
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Tetrahydroisoquinolines
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chemical synthesis
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chemistry
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pharmacology
7.Effect of phenolic alkaloids of Menispermum dauricum on thrombosis and platelet aggregation.
Acta Pharmaceutica Sinica 2005;40(10):916-919
AIMTo observe the effect of phenolic alkaloids of Menispermum dauricum (PAMD) on thrombosis and platelet aggregation, and to explore its mechanism of action.
METHODSThrombosis was observed with arteriovenous shunt thrombus model in rat; platelet aggregation was determined by Born's method; ultrastructure of platelet was observed by transmission electron microscope; TXB2 or 6-keto-PGF1alpha levels were assessed by radioimmunoassay; and NO was determined by colorimetric method.
RESULTSPAMD dose-dependently inhibited experimental thrombus formation, platelet aggregation induced by ADP, AA and THR in vivo and ultrastructure changes stimulated by THR; PAMD increased the generation of 6-keto-PGF1alpha in thoracic aortae and NO level in plasma; and had no influence on TXB2 release (P > 0.05).
CONCLUSIONPAMD inhibited thrombosis and platelet aggregation, and its mechanism might be due to the increase of PGI2 and NO level.
6-Ketoprostaglandin F1 alpha ; metabolism ; Alkaloids ; administration & dosage ; isolation & purification ; pharmacology ; Animals ; Aorta, Thoracic ; metabolism ; Benzylisoquinolines ; administration & dosage ; isolation & purification ; pharmacology ; Blood Platelets ; ultrastructure ; Dose-Response Relationship, Drug ; Epoprostenol ; metabolism ; Male ; Menispermum ; chemistry ; Nitric Oxide ; blood ; Plants, Medicinal ; chemistry ; Platelet Aggregation ; drug effects ; Rabbits ; Rats ; Rats, Sprague-Dawley ; Rhizome ; chemistry ; Tetrahydroisoquinolines ; administration & dosage ; isolation & purification ; pharmacology ; Thrombosis ; metabolism ; Thromboxane B2 ; metabolism
8.The influence on hemodynamics of myocardial ischemic dogs and blood pressure of animals with shenfu injection.
Fang-ju YANG ; Zheng-rong WANG ; Dai-ping LIN ; Yi QU ; Hua-hu YIN ; Li-li SHI ; Hui-ling GUO ; Jing XIAO ; Yue-qi WANG ; Rong-tao LIU
China Journal of Chinese Materia Medica 2003;28(3):259-262
OBJECTIVETo investigate the influence of Shenfu injection on the hemodynamic indexes of myocardial ischemic dogs and blood pressure of dogs and rats.
METHODMyocardial ischemic model was made and hypotension in the dogs was induced with ligating left front descending limb coronary artery method, and secondary hypertension by narrowing nephridium artery of rats, Shenfu injection was administered with 5, 10 mL.kg-1 to the above dogs and rats separately to investigate the influence of it on the hemodynamic indexes of myocardial ischemic dogs and blood pressure of rats.
RESULT AND CONCLUSIONShenfu injection enhanced the capacity of myocardial work markedly; it augmented the myocardium contractility and cardiac output without raising the oxygen consume, and at the same time it returned normal the blood pressure in myocardial ischemic; but it had no effects on the normal blood pressure and secondary hypertension of rats.
Aconitum ; chemistry ; Alkaloids ; isolation & purification ; pharmacology ; Animals ; Blood Pressure ; drug effects ; Dogs ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Ginsenosides ; isolation & purification ; pharmacology ; Hemodynamics ; drug effects ; Hypertension ; physiopathology ; Injections ; Male ; Myocardial Ischemia ; physiopathology ; Panax ; chemistry ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Tetrahydroisoquinolines ; isolation & purification ; pharmacology
9.The transport of gastrodin in Caco-2 cells and uptake in Bcap37 and Bcap37/MDR1 cells.
Acta Pharmaceutica Sinica 2010;45(12):1497-1502
Gastrodin (GAS) is the major bioactive component of the extracts from the rhizome of Gastrodia elata Blume. The aim of this study is to investigate the transport of GAS in Caco-2 cells and the interaction of P-glycoprotein and GAS. The apparent permeability coefficients (Papp) of GAS were measured as a function of directions and concentrations. It was demonstrated that the efflux ratio was < 2.0 over the range of 50-500 micromol x L(-1) of GAS from bi-directional transport studies. The transport rate of GAS was dependent on the concentrations. Papp of GAS was not affected by transport directions, GAS concentration or the classical inhibitors of P-glycoprotein (verapamil and GF 120918). The cellular accumulation of GAS in Bcap37/MDR1 cells transected with hMDR1 gene, was similar to that in Bcap37 cells. The accumulation in both cell lines was concentration dependent. GAS did not affect the accumulation of Rhodamine 123 in Bcap37/MDR1 cells over the range of 50-500 micromol x L(-1). It indicated that the transport of GAS in Caco-2 cell monolayers mainly is by passive paracellular transport pathway. P-glycoprotein did not participate in the absorption of GAS in the intestine or the transport across the blood-brain barrier.
ATP-Binding Cassette, Sub-Family B, Member 1
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antagonists & inhibitors
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metabolism
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Acridines
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pharmacology
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Benzyl Alcohols
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isolation & purification
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pharmacokinetics
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Biological Transport
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Blood-Brain Barrier
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Breast Neoplasms
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pathology
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Caco-2 Cells
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Cell Line, Tumor
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Drug Resistance, Multiple
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Gastrodia
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chemistry
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Glucosides
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isolation & purification
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pharmacokinetics
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Humans
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Plants, Medicinal
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chemistry
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Rhodamine 123
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pharmacokinetics
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Tetrahydroisoquinolines
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pharmacology
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Verapamil
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pharmacology
10.Effects of higenamine on the cardio-circulatory system.
China Journal of Chinese Materia Medica 2003;28(10):910-913
Higenamine (HG) is a potent cardioactive benzylisoquinoline alkaloid isolated from Aconiti tuber which has long been used as a cardiotonic in traditional Chinese medicine. HG exerts various effects on the cardio-circulatory system inotropic and chronotropic in isolated rat atria. It also relaxes isolated rat aorta. It inhibits epinephrine, ADP or collagen-induced platelet aggregation in platelet rich plasma. HG inhibits LPS-induced nitrate accumulation and the expression of iNOS mRNA in RAW 264.7 cells. HG lowers blood pressure in rats and increases the recovery rates in acute thrombosis model of mice, and lower the weight of thrombus formed in the arterio-venous shunt model of rats. Higenamine also has ameliorative effects in the LPS-induced DIC model.
Aconitum
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chemistry
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Alkaloids
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isolation & purification
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pharmacology
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therapeutic use
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Animals
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Blood Pressure
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drug effects
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Cardiotonic Agents
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pharmacology
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therapeutic use
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Disseminated Intravascular Coagulation
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drug therapy
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metabolism
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Fibrinolytic Agents
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pharmacology
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therapeutic use
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Humans
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Nitric Oxide Synthase
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biosynthesis
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genetics
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Nitric Oxide Synthase Type II
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Plants, Medicinal
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chemistry
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Platelet Aggregation
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drug effects
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RNA, Messenger
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biosynthesis
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genetics
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Tetrahydroisoquinolines
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isolation & purification
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pharmacology
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therapeutic use