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https://www.readbyqxmd.com/read/29341599/a-ni-catalyzed-carbon-carbon-bond-forming-reductive-amination
#1
Christoph Heinz, J Patrick Lutz, Eric M Simmons, Michael M Miller, William R Ewing, Abigail G Doyle
This report describes a three-component, Ni-catalyzed reductive coupling that enables the convergent synthesis of tertiary benzhydryl amines, which are challenging to access by traditional reductive amination methodologies. The reaction makes use of iminium ions generated in situ from the condensation of secondary N-trimethylsilyl amines with benzaldehydes, and these species undergo reaction with several distinct classes of organic electrophiles. The synthetic value of this process is demonstrated by a single-step synthesis of antimigraine drug flunarizine (Sibelium®) and high yielding derivatization of paroxetine (Paxil®) and metoprolol (Lopressor®)...
January 17, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29337184/when-drugs-plasticize-film-coatings-unusual-formulation-effects-observed-with-metoprolol-and-eudragit-rs
#2
Youness Karrout, Florence Siepmann, Youcef Benzine, Laurent Paccou, Yannick Guinet, Alain Hedoux, Juergen Siepmann
Metoprolol tartrate and metoprolol free base loaded pellet starter cores were coated with EudragitRS, plasticized with 25% triethyl citrate (TEC). The initial drug loading and coating level were varied from 10 to 40 and 0 to 20%, respectively. Drug release was measured in 0.1NHCl and phosphate buffer pH7.4. The water uptake and swelling kinetics, mechanical properties and TEC leaching of/from coated pellets and/or thin, free films of identical composition as the film coatings were monitored. The following unusual tendencies were observed: (i)the relative drug release rate from coated pellets increased with increasing initial drug content, and (ii)drug release from pellets was much faster for metoprolol free base compared to metoprolol tartrate, despite its much lower solubility (factor > 70)...
January 11, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29336242/the-influence-of-fatty-acids-on-metoprolol-human-serum-albumin-interaction-in-low-affinity-binding-sites-a-multifactorial-nmr-approach
#3
Agnieszka Szkudlarek, Mariusz Mogielnicki, Danuta Pentak, Anna Ploch, Malgorzata Maciazek-Jurczyk
The aim of the study was to evaluate the mechanism of interaction between metoprolol (MTP) and human serum albumin (HSA) using 1H NMR technique. The analysis of the drug-albumin interaction was based on the observed chemical shifts in combination with correlation times, 2D NOESY 1H NMR spectra and association constants and allowed us to observe the interactions between the aromatic rings of the drug and the amino acids of the protein. The binding of the drug, both in the hydrophobic subdomain and on the surface of the albumin, increases in the presence of fatty acids (FAs)...
January 15, 2018: Protein and Peptide Letters
https://www.readbyqxmd.com/read/29332839/magnetic-solid-phase-extraction-based-on-magnetic-multiwalled-carbon-nanotubes-for-the-simultaneous-enantiomeric-analysis-of-five-%C3%AE-blockers-in-the-environmental-samples-by-chiral-liquid-chromatography-coupled-with-tandem-mass-spectrometry
#4
Zhaokun Wang, Xue Zhang, Shenmeng Jiang, Xingjie Guo
In this work, the magnetic multiwalled carbon nanotubes (Mag-MWCNTs) were prepared by self-assembly method and characterized by scanning electron microscopy, X-ray powder diffraction, energy dispersive X-ray and vibrating sample magnetometer. Then, these synthetic Mag-MWCNTs were used as sorbents to extract five β-blockers (atenolol, metoprolol, esmolol, pindolol and arotinolol) by magnetic solid-phase extraction. The target analytes adsorbed on Mag-MWCNTs were eluted and determined on a chiral α-acid glycoprotein column coupled with a triple quadrupole mass spectrometry...
April 1, 2018: Talanta
https://www.readbyqxmd.com/read/29332838/rapid-and-sensitive-tapered-capillary-microextraction-combined-to-on-line-sample-stacking-capillary-electrophoresis-for-extraction-and-quantification-of-two-beta-blockers-in-human-urine
#5
Shucheng Sun, Yujia Wang, Xin Liu, Rao Fu, Li Yang
A tapered-capillary microextraction (tCap-μEx) combining with field-amplified stacking (FASI) method for CE analysis was developed. The tCap-μEx method is based on the construction of a micro solid phase extraction (SPE) column by narrowing the end of a silica capillary from 530µm (inner diameter) to 20µm, enabling the packing of 45µm sorbent particles without a frit. Various parameters that may affect the microextraction and FASI-CE analysis have been investigated and optimized. This study shows that microextraction exhibits advantages of small sample and sorbent volumes (less than 200μL sample and 2μL sorbent) and fast extraction time of 6min...
April 1, 2018: Talanta
https://www.readbyqxmd.com/read/29331894/pharmaceutical-concentration-variability-at-sewage-treatment-plant-outlets-dominated-by-hydrology-and-other-factors
#6
Andrea F Brunsch, Thomas L Ter Laak, Huub Rijnaarts, Ekkehard Christoffels
A study was conducted in which the effluent at four small to medium sized sewage treatment plants (STP) in North Rhine-Westphalia, Germany was monitored for three pharmaceutical compounds (carbamazepine, diclofenac, metoprolol) over a period of four years. Grab sampling and auto sampling campaigns were accomplished with respect to various weather conditions in the catchment area. Flow volumes and hydraulic retention times (HRT) from various sampling dates which provide information on processes causing emission changes were additionally taken into account...
January 11, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29327523/association-of-physicians-of-india-position-statement-on-role-of-chirally-pure-molecules-in-clinical-practice
#7
Milind Y Nadkar, Mangesh Tiwaskar, Sanjay Kalra, Siddharth N Shah, B R Bansode, Anjanlal Dutta, Sarita Bajaj, Sameer Aggarwal, Yatan Pal Singh Balhara, A K Das, Puneet Dhamija, Y K Gupta, Jubbin Jacob, Sundeep Mishra, S N Narasingan, C K Ponde, Ram Prabhoo, Balakrishnan S, Manisha Sahay, R K Sahay, I Sathyamurthy, Shilpa Tiwaskar, Agam Vora
Chirally pure molecules or enantiomers are non-superimposable mirror images of each other with a chiral center (such as carbon, sulphur, nitrogen or phosphorous atom). An equimolar mixture of enantiomers forms a racemate. Chirally pure molecules (single enantiomers) are important in the field of drug discovery as the drug targets such as enzymes and receptors are enantioselective in nature. Clinical studies have demonstrated that chirally pure drugs exhibit different pharmacokinetic and metabolic profiles, reduced adverse events, improved safety profiles and similar therapeutic activity at lowered drug dosage as compared with the racemate in many therapeutic areas...
December 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/29312582/shexiang-tongxin-dropping-pill-protects-against-isoproterenol-induced-myocardial-ischemia-in-vivo-and-in-vitro
#8
Jianyong Qi, Wenjun Pan, Yafang Tan, Jiaru Luo, Dancai Fan, Juan Yu, Jiashin Wu, Minzhou Zhang
Shexiang Tongxin dropping pill (STDP) is a formulae of Chinese Medicine commonly used to treating angina pectoris in China. However, its mechanism of action is still yet unclear. This study investigated the roles of STDP on myocardial ischemia injury. We constructed a rat model of myocardial injury (isoproterenol subcutaneous injection, i.h, 85 mg/kg/day for 2 days), and compared among 4 groups: CON (control), ISO (ischemic injury model), MET (metoprolol), and STDP. Serum contents of Troponin I (cTnI), creatine kinase (CK), CK-MB, lactate dehydrogenase (LDH), alpha-hydroxybutyric dehydrogenase (α-HBD), and Aspartate Aminotransferase were detected and five STDP doses (1, 10, 100, 1000 and 10000 mg/kg/day) were chosen to obtain a dose-response curve...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29301160/-pharmacotherapy-of-vestibular-disorders-nystagmus-and-cerebellar-disorders
#9
K Feil, N Böttcher, O Kremmyda, C Muth, J Teufel, A Zwergal, T Brandt, M Strupp
There are currently different groups of drugs for the pharmacotherapy of vertigo, nystagmus and cerebellar disorders: antiemetics; anti-inflammatories, antimenieres, and antimigraineous medications and antidepressants, anticonvulsants, aminopyridines as well as acetyl-DL-leucine. In acute unilateral vestibulopathy, corticosteroids improve the recovery of peripheral vestibular function, but currently there is not sufficient evidence for a general recommendation. There is insufficient evidence to support the view that 16 mg t...
January 2018: Laryngo- Rhino- Otologie
https://www.readbyqxmd.com/read/29285569/the-enigma-of-site-of-action-of-migraine-preventives-no-effect-of-metoprolol-on-trigeminal-pain-processing-in-patients-and-healthy-controls
#10
Julia M Hebestreit, Arne May
BACKGROUND: Beta-blockers are a first choice migraine preventive medication. So far it is unknown how they exert their therapeutic effect in migraine. To this end we examined the neural effect of metoprolol on trigeminal pain processing in 19 migraine patients and 26 healthy controls. All participants underwent functional magnetic resonance imaging (fMRI) during trigeminal pain twice: Healthy subjects took part in a placebo-controlled, randomized and double-blind study, receiving a single dose of metoprolol and placebo...
December 19, 2017: Journal of Headache and Pain
https://www.readbyqxmd.com/read/29260695/-jaundice-and-liver-injury-with-cholestatic-pattern-after-treatment-with-metoprololsuccinat
#11
Tommy Hansen, Lotte Fynne
Drug-induced liver injury is a well-known adverse event to numerous medications with clinical presentations from asymptomatic liver enzyme elevation to liver failure. However, liver injury after administration with metoprolol is not common, and only few case reports have been published. This is a case report of an 80-year-old woman with liver injury with cholestatic pattern and jaundice after two months of treatment with Metoprololsuccinat. With no evidence of other disease, liver function normalized in the following months after discontinuation of Metoprololsuccinat...
December 18, 2017: Ugeskrift for Laeger
https://www.readbyqxmd.com/read/29245279/mitral-regurgitation-after-anthracycline-based-chemotherapy-in-an-adult-patient-with-breast-cancer-a-case-report
#12
Xiaoyan Liu, Yanlin Zhu, Xue Lin, Ligang Fang, Xiaowei Yan
RATIONALE: Anthracyclines cardiotoxicity characterized by dilated myocardiopathy has been well described in the literature. However, anthracyclines-induced valvular diseases have been seldom reported. PATIENT CONCERNS: In this study, we present the case of a 62-year-old Chinese female patient with breast cancer developing severe mitral regurgitation after anthracycline exposure. DIAGNOSES: The patient was diagnosed with mitral regurgitation with preserved left ventricular ejection fraction and normal cardiac chamber dimensions in the sixth month after the last course of anthracycline-containing chemotherapy...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29241133/oxidation-of-%C3%AE-blockers-by-birnessite-kinetics-mechanism-and-effect-of-metal-ions
#13
Yong Chen, Xiye Lu, Lu Liu, Dong Wan, Huabin Chen, Danna Zhou, Virender K Sharma
Manganese dioxides are ubiquitous in natural waters, soils, and sediments and play an important role in oxidative transformation of organic pollutants. This work presents the kinetics of the oxidation of selected β-blockers, betaxolol, metoprolol, and atenolol by birnessite (δ-MnO2) as a function of concentration of the β-blocker, dosage of δ-MnO2, and solution pH. The values of pseudo-first-order rate constants (kobs) of β-blockers decreased in the order betaxolol > atenolol > metoprolol, which was positively correlated with their acid dissociation constants (Ka)...
December 6, 2017: Chemosphere
https://www.readbyqxmd.com/read/29232194/persistent-ventricular-bigeminy-during-anesthesia-in-pediatric-patients-a-case-report-of-an-11-year-old-child
#14
Sheetal Dalal, Vikas Chaudhari
An 11-year-old male child with fractures in both bones in his left forearm presented for open reduction and internal fixation. The pre-anesthetic check-up and investigations did not reveal any pre-existing underlying cardio-respiratory disease. The patient had an uneventful peri-operative period during the operation and was comfortable without any anxiety or restlessness. After an uneventful induction and intubation as per routine protocol, the patient received 600 mg of amoxicillin+clavunate intravenously as an antibiotic...
December 12, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/29218065/acute-myocardial-injury-in-a-child-with-duchenne-muscular-dystrophy-pulse-steroid-therapy
#15
Eliza Cinteza, Claudiu Stoicescu, Niculina Butoianu, Mihaela Balgradean, Alin Nicolescu, Matthias Angrés
Heart implication in Duchenne muscular dystrophy usually is present in the form of dilated cardiomyopathy, manifested as heart failure and arrhythmias. To delay progression, including heart deterioration, prednisone is recommended as preventive treatment. We report the case of an 11-year-old boy diagnosed with Duchenne muscular dystrophy at the age of seven, who was on preventive treatment with oral prednisone (0.75 mg/kg/day) and beta blocker (metoprolol, 1 mg/kg/day). Suddenly, the patient presented acute chest pain, vomiting and sweating...
September 2017: Mædica
https://www.readbyqxmd.com/read/29209976/do-cemeteries-emit-drugs-a-case-study-from-southern-germany
#16
Sabine Fiedler, Torsten Dame, Matthias Graw
The risk of earth burials for the environment and public health is a matter of controversial debate. The aim of the present study is to characterise the drainage of cemeteries with regard to the concentration of a number of pharmaceuticals and to the soil's hydrochemical properties, and to discuss these data in comparison with data obtained for surface waters located upstream of the cemeteries. Of the 12 drainage samples analysed using LC-ESI-MS/MS, seven contained carbamazepine (< 225 ng l-1), five contained hydrochlorothiazide, one contained metoprolol (23 ng l-1) and one contained traces of ibuprofen...
December 6, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29193283/diastolic-dysfunction-in-pulmonary-artery-hypertension-creatine-kinase-and-the-potential-therapeutic-benefit-of-beta-blockers
#17
Ewan D Fowler, Mark J Drinkhill, Rachel Stones, Ed White
Passive properties of the myocardium influence diastolic filling and cardiac output. In heart failure, changes in contributors to the passive properties of the ventricle, such as titin and collagen, and loss of the metabolic enzyme creatine kinase, increase resistance to filling resulting in diastolic dysfunction. Pulmonary artery hypertension (PAH) arises from interactions between the pulmonary vasculature and the right ventricle (RV) which ultimately leads to RV failure. Beta1-adrenergic receptor blockers (BB) act on the myocardium and are beneficial in left heart failure but are not used in PAH...
November 28, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29193123/physiologically-based-pharmacokinetic-modeling-to-evaluate-the-systemic-exposure-of-gefitinib-in-cyp2d6-ultrarapid-metabolizers-and-extensive-metabolizers
#18
Yingxue Chen, Diansong Zhou, Weifeng Tang, Wangda Zhou, Nidal Al-Huniti, Eric Masson
Gefitinib is a selective inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase and is used for the treatment of non-small-cell lung cancer (NSCLC) with activating EGFR mutations. Gefitinib is metabolized by CYP2D6 and CYP3A4. This analysis compared the systemic exposure of gefitinib after oral administration in CYP2D6 ultrarapid metabolizers (UM) vs extensive metabolizers (EM). Physiologically based pharmacokinetic (PBPK) modeling was conducted using a population-based simulator. The model was calibrated using itraconazole-gefitinib clinical drug-drug interaction data and validated with gefitinib data in CYP2D6 EM vs poor metabolizers (PM)...
November 28, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29172846/use-of-beta-blockers-is-associated-with-hearing-loss
#19
Bandar Saeed Al-Ghamdi, Dileep Kumar Rohra, Gheid Ali Ibrahim Abuharb, Hala Abdulrahman Alkofide, Nadiah Salem AlRuwaili, Mohamed M Shoukri, Peter M B Cahusac
OBJECTIVE: This study was conducted to investigate the hypothesis that patients using β-blockers will develop hearing loss. DESIGN: A cross-sectional study. STUDY SAMPLE: A total of 125 patients completed the study. A total of 63 patients were on β-blockers and 62 were not on β-blockers. RESULTS: Carvedilol was significantly associated with hearing loss. Other beta-blockers including metoprolol and atenolol showed no association with hearing loss...
November 24, 2017: International Journal of Audiology
https://www.readbyqxmd.com/read/29162627/a-therapeutic-combination-of-gpcr-modulators-that-protects-photoreceptors-from-degeneration
#20
Tivadar Orban, Henri Leinonen, Tamar Getter, Zhiqian Dong, Wenyu Sun, Songqi Gao, Alexander Veenstra, Hossein Heidari-Torkabadi, Timothy S Kern, Philip D Kiser, Krzysztof Palczewski
Degeneration of retinal photoreceptor cells can arise from environmental and/or genetic causes. Since photoreceptor cells, the retinal pigment epithelium (RPE), neurons and glial cells of the retina are intimately associated; all cell types eventually are affected by retinal degenerative diseases. Such diseases often originate either in rod and/or cone photoreceptor cells or the RPE. Of these, cone cells located in the central retina are especially important for daily human activity. Here we describe the protection of cone cells by a combination therapy consisting of the G protein-coupled receptor modulators metoprolol, tamsulosin, and bromocriptine...
November 21, 2017: Journal of Pharmacology and Experimental Therapeutics
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