A major goal in pharmacokinetic-pharmacodynamic (PK/PD) modeling of neuromuscular blockade (NMB) is to quantitatively estimate the dose-response relationship.Our PK/PD model consists of three submodels:PK, link kinetics, and PD.A virtual effect compartment in which the drug concentration is in equilibrium with the observed concentration is used to extract the kinetic component (keo) from the pharmacodynamic data alone.Parameters of this model are keo, Ce(50), and gamma.The underlying structural pharmacokinetics and pharmacodynamics for NMB have been well understood, and new novel PK/PD models have been substituted for the gold standard PK/PD model for NMB.The purpose of this review was to describe progress in the field of PK/PD modeling of NMB from the first model, a simultaneous PK/PD model developed by Sheiner et al in the 1970s, to some of the more complicated models.Specific PK/PD models, which accurately described the behaviors of rocuronium, mivacurium, atracurium, and cisatracurium, include the recirculatory model, the peripheral link model, the peripheral elimination model, and a nonparametric model for link kinetics.
Aluminum Hydroxide ; Androstanols ; Atracurium ; Carbonates ; Isoquinolines ; Kinetics ; Neuromuscular Blockade

Adolescent ; Adult ; Asthma ; drug therapy ; Czechoslovakia ; History of Medicine ; Humans ; Injections, Subcutaneous ; Isoquinolines ; administration & dosage ; Mental Disorders ; drug therapy ; Psychiatry ; history ; Terbutaline ; administration & dosage ; therapeutic use ; Tranquilizing Agents ; history ; therapeutic use ; Tretoquinol ; administration & dosage ; therapeutic use

AIMTo study the alkaloid constituents of the root of Lindera angustifolia Cheng.

METHODSThe constituents were isolated and purified by column chromatography and the structures were characterized by spectral analysis.

RESULTSSeven aporphine alkaloids, laurotetanine (I), N-methyllaurotetanine (II), boldine (III), isoboldine (IV), norboldine (V), N-ethoxycarbonyllaurotetanine (VII) and a quaternary isoquinoline alkaloid, magnocurarine (VI), were isolated and identified. The structure of VII was further identified by semi-synthesis with I as starting material.

CONCLUSIONAll compounds were obtained from this plant for the first time and compound VII was found as a naturally occurring compound for the first time.

Alkaloids ; chemistry ; isolation & purification ; Aporphines ; chemistry ; isolation & purification ; Isoquinolines ; chemistry ; isolation & purification ; Lindera ; chemistry ; Molecular Conformation ; Molecular Structure ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry

Absorption of papaverine (PAP), laudanosine (LAU) and cepharanthine (CEP) as some chemical constituents of traditional Chinese medicines in human intestine were studied. By using Caco-2 (the human colonic adenocarcinoma cell lines) cell monolayers as an intestinal epithelial cell model, the permeability of PAP, LAU and CEP were studied from apical side (AP side) to basolateral side (BL side) or from BL side to AP side. The three alkaloids were measured by reversed-phase high-performance liquid chromatography coupled with UV detector. Transport parameters and apparent permeability coefficients (Papp) were then calculated and compared with those of propranolol as a control substance of high permeability and atenolol as a control substance of poor permeability. The Papp values of PAP, LAU and CEP were (3.524+/-0.223) x 10(-5), (2.821+/-0.050) x 10(-5) and (6.524+/-0.052) x 10(-5) cm s(-1) from AP side to BL side, and (5.095+/-0.508) x 10(-5), (2.646+/-0.146) x 10(-5) and (5.495+/-0.036) x 10(-5) cm s(-1) from BL side to AP side, respectively. Their Papp values were identical with those of propranolol, which is a transcellular transport marker. On the other hand, the efflux transport of PAP was 1.45 times higher than its influx transport with 0.69 rate of P(app A-->B)/P(app B-->A). But P(app A-->B)/P(app B-->A) values of LAU and CEP were 1.07 and 1.19, respectively, which suggested that the efflux transport have not been involved in their absorbed mechanism in Caco-2 cells monolayers. There is a good correlation between the Papp value and apparent distribution coefficient (Log D) at pH 7.35 for the three alkaloids. PAP, LAU and CEP can be absorbed across intestinal epithelial cells, and they are completely absorbed compounds. PAP may have been involved in efflux mechanism in Caco-2 cells monolayers model from the basolateral-to-apical direction. The O/W (oil/water) partition coefficient plays key role in their transmembrane permeation.
Benzylisoquinolines ; analysis ; isolation & purification ; pharmacokinetics ; Biological Transport ; Caco-2 Cells ; Cell Membrane Permeability ; Chromatography, High Pressure Liquid ; methods ; Epithelial Cells ; metabolism ; Humans ; Intestinal Absorption ; Isoquinolines ; analysis ; isolation & purification ; pharmacokinetics ; Papaverine ; analysis ; isolation & purification ; pharmacokinetics ; Plants, Medicinal ; chemistry

Mivacurium is mainly metabolized by plasma cholinesterase, whereas atracurium is removed by Hofman elimination. The purpose of this study was to compare the infusion rate of atracurium and mivacurium in maintaining surgical relaxation, and to compare their recovery indices between parturients and non-pregnant women. Muscle relaxation was maintained by the continuous infusion of relaxants to retain the first response of train-of-four (TOF) at 5% of control. When mivacurium was used, Bolus-T5 (duration from the end of mivacurium bolus injection to 5% single twitch recovery) was measured. After discontinuing the infusion, the recovery index was measured. The infusion rate of mivacurium, not atracurium, was significantly lower in parturients and Bolus-T5 of parturients was significantly longer than that of non-pregnant women. There was no significant difference in the recovery indices of both relaxants. The authors concluded that the infusion rate of mivacurium in maintaining muscle relaxation in parturients should be reduced compared to the rate in non-pregnant women and measuring Bolus-T5 may be helpful in determining the infusion rate to maintain muscle relaxation.
Adult ; Atracurium/therapeutic use ; Atracurium/administration & dosage* ; Cesarean Section* ; Comparative Study ; Female ; Human ; Injections, Intramuscular ; Isoquinolines/therapeutic use ; Isoquinolines/administration & dosage* ; Neuromuscular Nondepolarizing Agents/therapeutic use ; Neuromuscular Nondepolarizing Agents/administration & dosage* ; Pregnancy

No abstract available.
Papaverine*

No abstract available.
Papaverine*

A new isoquinoline alkaloid(1) has been isolated from the whole plant of Thalictrum glandulosissimum by using various chromatographic techniques, including silica gel, sephadex, MCI-gel resin, and RP-HPLC, and its structure was determined as 1-(6-hydroxy-7-methylisoquinolin-1-yl) ethantone by physicochemical properties and spectroscopic data. This compound was evaluated for anti-tobacco mosaic virus(TMV) activity. The results showed that it had prominent anti-TMV activity with inhibition rates of 28.4%. This rate was closed to that of positive control.
Alkaloids ; Antiviral Agents ; Isoquinolines ; Thalictrum ; Tobacco Mosaic Virus

Coptidis Rhizoma is a common Chinese medicinal in clinical practice,with the effects of clearing heat,drying dampness,purging fire,and removing toxin. All the medicinal plants of Coptis can be used for clinical treatment,but some species are endangered due to resource destruction and difficulty in planting. The dominant medicinal components in Coptidis Rhizoma are isoquinoline alkaloids. There are various methods for the analysis and detection of alkaloids,such as LC-MS,HPLC,and TLC,among which LC-MS is the most widely applied. Different plants of Coptis vary in the kind and content of alkaloids. C. chinensis,C. deltoidea,C. teeta,C. chinensis var. brevisepala,C. omeiensis,C. quinquefolia,and C. quinquesecta mainly contain berberine,palmatine,coptisine,jatrorrhizine,and columbamine,five effective alkaloid components. Plant isoquinoline alkaloids( PIAs) have strong pharmacological activity but are difficult to prepare. The application of synthetic biology of PIAs will be helpful for the clinical application of PIAs. This paper reviews the research progress on biological resources of Coptis species and structures of alkaloids as well as analysis methods and synthetic biology for isoquinoline alkaloids in the medicinal plants of Coptis in recent years,which will facilitate the protection of Coptis medicinal resources and the application and development of alkaloids.
Alkaloids ; Berberine ; Berberine Alkaloids ; Coptis ; Drugs, Chinese Herbal ; Isoquinolines ; Rhizome

A strategy combining collision cross section(CCS) prediction and quantitative structure-retention relationship(QSRR) model for quinoline and isoquinoline alkaloids was established based on UHPLC-IM-Q-TOF-MS and applied to Phellodendri Chinensis Cortex and Phellodendri Amurensis Cortex. The strategy included the following three steps.(1) The molecular features were extracted by the "find features" algorithm.(2) The potential quinoline and isoquinoline alkaloids were screened by filtering the original characteristic ions extracted from Phellodendri Chinensis Cortex and Phellodendri Amurensis Cortex by the established CCS vs m/z prediction interval.(3) According to the retention time of candidate compounds predicted by QSRR model, the chemical constituents were identified in combination with the characteristic fragment ions and pyrolysis law of secondary mass spectrometry. With the strategy, a total of 80 compounds were predicted, and 15 were identified accurately. The strategy is effective for the identification of small analogs of traditional Chinese medicine.
Chromatography, High Pressure Liquid ; Algorithms ; Alkaloids ; Isoquinolines ; Quinolines