Eschscholtzia californica preparations are in use as phytopharmaceuticals and as herbal drugs. Studies are described on the metabolism and the toxicological analysis of the Eschscholtzia californica alkaloids californine and protopine in rat urine using gas chromatography-mass spectrometry. ... Protopine ... undergoes extensive demethylenation of the 2,3-methylenedioxy group followed by catechol-O-methylation. All phenolic hydroxy metabolites were found to be partly conjugated. The authors' systematic toxicological analysis procedure using full-scan gas chromatography-mass spectrometry after acid hydrolysis, liquid-liquid extraction and microwave-assisted acetylation allowed the detection of the main metabolites of californine and protopine in rat urine after a dose which should correspond to that of drug users. Therefore, use of Eschscholtzia californica preparations should also be detectable in human urine by the authors' systematic toxicological analysis procedure.
IDENTIFICATION AND USE: Protopine is a solid. It is used as medication. HUMAN EXPOSURE AND TOXICITY: Using gene reporter assays performed in transiently transfected HepG2 cells, it was demonstrated that the induction of CYP1A1 expression by protopine was associated with mild or negligible activation of the aryl hydrocarbon receptor. CYP1A mRNA levels induced by protopine in both HepG2 cells and human hepatocytes did not result in elevated CYP1A protein or activity levels. ANIMAL STUDIES: Protopine showed an ability to enhance gamma-aminobutyric acid binding to rat brain synaptic membrane receptors in in vitro radiolabeling studies. Protopine has antiarrhythmic effects and may directly inhibit rapid electrical activity of cardiac cells.
Protopine has been found to inhibit histamine H1 receptors and platelet aggregation, and acts as an analgesic. It is one of the compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS. Protopine can selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Classical antihistaminics antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. Protopine can also function as platelet aggregation inhibitors which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system. Protopine inhibits the contractility of isolated cardiac papillary muscles and the proliferation of vascular smooth muscle cells induced by endothelin. It also shortens action potential duration and prolongs the effective refractory period in guinea pig cardiac papillary muscles. The protective effect on rat heart from ischemia_reperfusion damage and the relaxation of rat thoracic aorta induced by protopine have been related to the inhibition of Ca2+ influx through both voltage- and receptor-operated Ca2+ channels. Protopine has been the focus of a large number of biological studies in which they both exhibited, for instance, anti-parasitic activity and only weak cytotoxicity in comparison with other types of isoquinoline alkaloids. Protopine was found to be cytoprotective against oxidative stress induced cell death in vitro. The alkaloid was shown to have anti-arrhythmic, anti-thrombotic, anti-inflammatory, and hepatoprotective effects in animal models. The biological activity of protopine may be associated with its ability to inhibit calcium, sodium, and potassium channels. (PMID:15588728; PMID:21419197; L2104)
来源:Toxin and Toxin Target Database (T3DB)
毒理性
致癌物分类
对人类不具有致癌性（未被国际癌症研究机构IARC列名）。
No indication of carcinogenicity to humans (not listed by IARC).
The antiarrhythmic effects of protopine on experimental arrhythmia were studied in various animals. Protopine elevated the dose of aconitine needed to induce VP, VT, and VF in rats and increased the dose of strophanthin (strophanthine K) that induced VP in guinea pigs. It also shortened the duration of central arrhythmia induced by aconitine and the duration of arrhythmia induced by benzene-epinephrine (adrenaline) in rats. It prevented rats and mice from developing arrhythmia induced by intravenous calcium chloride and inhalation of chloroform, respectively. In rabbits, the drug raised VFT. It was concluded that protopine has antiarrhythmic effects and may directly inhibit rapid electrical activity of cardiac cells.
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
Xiang-Fu-Si-Wu Decoction (XFSWD) has been widely used to treat primary dysmenorrhea in clinical practice for hundreds of years and shown great efficacy. One fraction of XFSWD, which was an elution product by macroporous adsorption resin from aqueous extract solution with 60% ethanol (XFSWE), showed great analgesic effect. The present study was conducted to investigate the possible pharmacokinetic and tissue distribution profiles of four major bioactive constituents (berberine, protopine, tetrahydrocoptisine and tetrahydropalmatine) after oral administration of XFSWE in dysmenorrheal symptom rats, and to compare the difference between normal and dysmenorrheal symptom rats. Estradiol benzoate and oxytocin were used to produce dysmenorrheal symptom rat model. The experimental period was seven days. At the final day of experimental period, both normal and dysmenorrheal symptom rats were orally administrated with XFSWE, and then the blood and tissues samples were collected at different time points. Berberine, protopine, tetrahydrocoptisine and tetrahydropalmatine in blood and tissue samples were determined by LC-MS/MS. Pharmacokinetic parameters were calculated from the plasma concentration-time data using non-compartmental methods. The differences of pharmacokinetic parameters among groups were tested by one-way analysis of variance (ANOVA). There were statistically significant differences (P<0.05) in Cmax, Tmax, AUC(0-t), AUC(0-infinity), MRT(0-t), MRT(0-infinity) and CL/F between normal and dysmenorrheal symptom rats that orally administered with same dosage of XFSWE. In tissue distribution study, the results showed that the overall trend was C(Spleen)>C(Liver)>C(Kidney)>C(Uterus)>C(Heart)>C(Lung)>C(Ovary)>C(Brain)>C(Thymus), C(M-60 min)>C(M-120 min)>C(M-30 min)>C(C-60 min)>C(C-120 min)>C(C-30 min). The contents of protopine in liver, spleen and uterus were more than that in other tissues of dysmenorrheal symptom rats. Compared to normal rats, partial contents of the compounds in dysmenorrheal symptom rats' tissues at different time points had significant difference (P<0.05). This study was the first report about pharmacokinetic and tissue distribution investigation in dysmenorrheal symptom animals. The results indicated that berberine, protopine, tetrahydrocoptisine and tetrahydropalmatine have higher uptake and slower elimination in the rats with dysmenorrheal syndrome, which suggests that the rate and extent of drug metabolism were altered in dysmenorrheal syndrome rats. And the results also demonstrated that berberine, protopine and tetrahydropalmatine in normal and dysmenorrheal symptom rats had obvious differences in some organs and time points, suggesting that the blood flow and perfusion rate of the organ were altered in dysmenorrheal symptom animals.
为了合成原松碱生物碱，我们研究了基于单重氧合氧化茚并[2,1- a ] [3]苯并ze庚因的环扩大，然后转化所得的10元酰胺基的反应顺序。酮内酰胺成亚甲基，这是完成合成的最后一步。关键物质茚并[2,1- a ] [3]苯并ze庚因是通过Bischler-Napieralski环化烷氧基取代的1-（2-溴苄基）-3-苯并ze庚因-2-酮制备的。检查了该合成中取代基的立体效应。
[EN] COMPOSITIONS AND METHODS FOR MAKING NOSCAPINE AND SYNTHESIS INTERMEDIATES THEREOF<br/>[FR] COMPOSITIONS ET PROCÉDÉS DE FABRICATION DE NOSCAPINE ET D'INTERMÉDIAIRES DE SYNTHÈSE DE CELLE-CI
申请人：EPIMERON INC
公开号：WO2015021561A1
公开（公告）日：2015-02-19
Methods for the manufacture of the therapeutic chemical compound noscapine and noscapine synthesis intermediates comprising contacting a noscapine pathway precursor selected from a first canadine derivative, a first papaveroxine derivative and narcotine hemiacetal with at least one of the enzymes selected from the group CYP82Y1, CYP82X1, AT1, CYP82X2, OMT, CXE1 and NOS.
A series of isoquinoline alkaloids including tetrahydroprotoberberines, N-methyl tetrahydroprotoberberines and protoberberines were facile synthesised with protopines as the starting material. All compounds were evaluated for their antibacterial activities against four pathogenic bacteria Escherichia coli, Staphyloccocus aureus, Staphylococcus gallinarum and Salmonella choleraesuis. Experimental results
申请人：DALIAN INSTITUTE OF CHEMICAL PYSICS, CHINESE ACADEMY OF SCIENCES
公开号：US20150164870A1
公开（公告）日：2015-06-18
A method of treating nervous system diseases associated with dopamine receptors comprising administering a patent in need a compound having a structure of general formula (I) or a pharmaceutical acceptable salt, hydrate, or solvate thereof in a pharmaceutically effective amount, and a method of making the compound having the structure of general formula (I) or a pharmaceutical acceptable salt, hydrate, or solvate thereof. The compound of formula (I) has multiple pharmacological functions such as the functions of activating opioid receptors and blocking dopamine D2 receptors, and has good physicochemical properties and oral bioavailability. General animal experiments show that such a compound has significant and long-lasting analgesic and calming effects and can be used to treat pain and other mental illnesses.
Utilization of protopine and related alkaloids. XVII. Spectroscopic studies on the ten-membered ring conformations of protopine and .ALPHA.-allocryptopine.
作者：HIROSHI TAKAHASHI、MIEKO IGUCHI、MASAYUKI ONDA
DOI：10.1248/cpb.33.4775
日期：——
The infrared carbonyl absorptions of protopine and α-allocryptopine in dilute carbon tetrachloride solution and nuclear Overhauser effect experiments in the proton nuclear magnetic resonance spectra have shown that these alkaloids each interconvert between two major conformations of the ten-membered ring. These conformations are discussed on the basis of the observed spectral data.
[EN] QUATERNARY ALKALOID DERIVATIVES OF CHELIDONIUM MAJUS L<br/>[FR] DERIVES ALCALOIDES QUATERNAIRES DE CHELIDONIUM MAJUS L
申请人：NOWICKY WASSILI
公开号：WO2006032380A1
公开（公告）日：2006-03-30
The invention relates to alkaloid reaction products obtainable in a process wherein alkaloids are reacted with a derivatizing agent, preferably thiotepa or another one of the compounds listed in Fig.3, whereafter unreacted derivatizing agent and other water-soluble compounds are removed from the reaction mixture by washing with water or a suitable aqueous solvent, whereafter the reaction mixture is subjected to a treatment with strong acid, preferably hydrogen chloride (HCI), to precipitate a water soluble salt of the reaction products. The precipitated reaction products comprise at least one quaternary alkaloid derivative and are suitable as drugs for prophylactic or therapeutic application, particularly in the treatment of immunological or metabolic dysfunctions, and cancer.
