- Large-scale in silico identification of drugs exerting sex-specific effects in the heart. [Journal Article]
- JTJ Transl Med 2018 Aug 29; 16(1):236
- CONCLUSIONS: We conclude that our in silico model could be translated into clinical practice to predict sex-specific drug responses, thereby contributing towards a more appropriate medical care for both men and women.
- Drugs and Lactation Database (LactMed) [BOOK]
- BOOKNational Library of Medicine (US): Bethesda (MD)
- Because of the relatively extensive excretion of acebutolol and its active metabolite diacetolol into breastmilk and their extensive renal excretion, other agents may be preferred, especially while n...
Because of the relatively extensive excretion of acebutolol and its active metabolite diacetolol into breastmilk and their extensive renal excretion, other agents may be preferred, especially while nursing a newborn or preterm infant.
- StatPearls [BOOK]
- BOOKStatPearls Publishing: Treasure Island (FL)
- The cardio-selective beta blockers include atenolol, betaxolol, bisoprolol, esmolol, acebutolol, metoprolol, and nebivolol. FDA approved uses of beta-1-selective blockers include hypertension, chroni...
The cardio-selective beta blockers include atenolol, betaxolol, bisoprolol, esmolol, acebutolol, metoprolol, and nebivolol. FDA approved uses of beta-1-selective blockers include hypertension, chronic stable angina, heart failure, post-myocardial infarction, and decreased left ventricular function after a recent myocardial infarction. Non-FDA approved uses include migraine prophylaxis, treatment of arrhythmias, tremor reduction, and the symptomatic treatment of anxiety disorders. Their use is associated with decreased morbidity and mortality post-myocardial infarction. Treatment with beta-1 blockers decreases the risk of stroke, coronary artery disease, and congestive heart failure.
- Sol-gel based biogenic silica composite as green nanosorbent for chemometric optimization of micro-solid-phase extraction of beta blockers. [Journal Article]
- JCJ Chromatogr A 2018 Jun 15; 1554:16-27
- An environmentally friendly micro-solid phase extraction (μ-SPE) method utilizing a plant based nanocomposite as a sorbent for determination of trace level beta blockers (β-blockers) in hospital wast...
An environmentally friendly micro-solid phase extraction (μ-SPE) method utilizing a plant based nanocomposite as a sorbent for determination of trace level beta blockers (β-blockers) in hospital wastewater prior to Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. μ-SPE extraction conditions were evaluated using a multivariate chemometric approach. Rice husk silica-carbon nanocomposite (5-20Wt.% Fe) in glycerol were synthesized via hydrolytic sol-gel method. The nanosorbent were fully characterized and then evaluated for μ-SPE of trace level β-blockers in hospital wastewater. To establish the best extraction conditions at minimal experimental cost, multivariate techniques based on fractional factorial (FFD) and central composite designs (CCD) with desirability function (DF) were used to optimize the extraction conditions. Experimental results showed good agreement with predicted values and logical DF was realized at relatively low extraction time. Under optimized conditions, good linearity ranges (0.02-5.0μgL-1) with correlation of determinations higher than 0.9954 were obtained. The limits of detection and quantitation for the five β-blockers (atenolol, alprenolol, pindolol, acebutolol and propranolol) ranged from 4.0-6.4 and 13.0-19.0ngL-1, respectively. Inter-day and intra-day precision (percent relative standard deviations, n=5) were lower than 8.3% while relative recoveries for hospital wastewater samples (80.6-105.1%) were in satisfactory ranges. This experimental approach therefore, demonstrated simplicity, reduction in the experimental runs, effectively increased sensitivity of LC-MS/MS and was hence suitable for complex matrix sample analysis.
- Acebutolol, a Cardioselective Beta Blocker, Promotes Glucose Uptake in Diabetic Model Cells by Inhibiting JNK-JIP1 Interaction. [Journal Article]
- BTBiomol Ther (Seoul) 2018 Sep 01; 26(5):458-463
- The phosphorylation of JNK is known to induce insulin resistance in insulin target tissues. The inhibition of JNK-JIP1 interaction, which interferes JNK phosphorylation, becomes a potential target fo...
The phosphorylation of JNK is known to induce insulin resistance in insulin target tissues. The inhibition of JNK-JIP1 interaction, which interferes JNK phosphorylation, becomes a potential target for drug development of type 2 diabetes. To discover the inhibitors of JNK-JIP1 interaction, we screened out 30 candidates from 4320 compound library with In Cell Interaction Trap method. The candidates were further confirmed and narrowed down to five compounds using the FRET method in a model cell. Among those five compounds, Acebutolol showed notable inhibition of JNK phosphorylation and elevation of glucose uptake in diabetic models of adipocyte and liver cell. Structural computation showed that the binding affinity of Acebutolol on the JNK-JIP1 interaction site was comparable to the known inhibitor, BI-78D3. Our results suggest that Acebutolol, an FDA-approved beta blocker for hypertension therapy, could have a new repurposed effect on type 2 diabetes elevating glucose uptake process by inhibiting JNK-JIP1 interaction.
- Discovery of Potent Neuraminidase Inhibitors Using a Combination of Pharmacophore-Based Virtual Screening and Molecular Simulation Approach. [Journal Article]
- ABAppl Biochem Biotechnol 2018; 184(4):1421-1440
- Neuraminidase (NA), a surface protein, facilitates the release of nascent virus and thus spreads infection. It has been renowned as a potential drug target for influenza A virus infection. The drugs ...
Neuraminidase (NA), a surface protein, facilitates the release of nascent virus and thus spreads infection. It has been renowned as a potential drug target for influenza A virus infection. The drugs such as oseltamivir, zanamivir, peramivir, and laninamivir are approved for the treatment of influenza infection. Additionally, investigational drugs namely MK2206, tamiphosphor, crenatoside, and dehydroepiandrosterone (DHEA) are also available for the treatment. However, recent outbreaks of highly pathogenic and drug-resistant influenza A strains highlighted the need to discover novel NA inhibitor. Keeping this in mind, in the current investigation, an effort was made to ascertain potent inhibitors using pharmacophore-based virtual screening and docking approach. A 3D pharmacophore model was generated based on the chemical features of approved and investigational NA inhibitors using PHASE module of Schrödinger suite. The model consists of two hydrogen bond acceptors (A), one hydrogen bond donor (D), and one positively charged group (P), AADP. Subsequently, molecules with same pharmacophoric features were screened from among the two million compounds available in the ZINC database using the generated pharmacophore hypothesis. Ligand filtration was also done to obtain an efficient collection of hit molecules by employing Lipinski "rule of five" using Qikprop module. Finally, the screened molecule was subjected to docking and molecular dynamic simulations to examine the inhibiting activity of the compounds. The results of our analysis suggest that "acebutolol hydrochloride" (156792) could be the promising candidates for the treatment of influenza A virus infection.
- Whole body physiologically based modelling of β-blockers in the rat: events in tissues and plasma following an i.v. bolus dose. [Journal Article]
- BJBr J Pharmacol 2018; 175(1):67-83
- CONCLUSIONS: PBPK modelling is a very powerful tool to aid drug discovery and development of therapeutic agents in animals and humans. However, careful consideration of the assumptions made during the modelling exercise is essential.
- Structural characterization of electrochemically and in vivo generated potential metabolites of selected cardiovascular drugs by EC-UHPLC/ESI-MS using an experimental design approach. [Journal Article]
- TTalanta 2018 Jan 01; 176:262-276
- In the last few years, a number of studies were conducted which aimed at understanding the mechanisms of cardiovascular drug, metabolism, and there is still the need to determine the metabolites of c...
In the last few years, a number of studies were conducted which aimed at understanding the mechanisms of cardiovascular drug, metabolism, and there is still the need to determine the metabolites of cardiac drugs for the purpose of metabolism control. In this study, we employ a direct combination of electrochemical oxidation and mass spectrometric (EC-MS) identification for monitoring the oxidation pathway of ten cardiovascular drugs (metoprolol, propranolol, propafenone, mexiletine, oxprenolol, pirbuterol, pindolol, cicloprolol, acebutolol and atenolol). Oxidation was accomplished in an electrochemical thin-layer cell coupled on-line to electrospray ionization mass spectrometry (EC/ESI-MS). For further characterization of electrochemical products, the approach involving liquid chromatography linked to tandem mass spectrometry was used. Appropriate conditions for oxidation and identification processes with such parameters as the potential value, mobile phase (type and pH) and working electrode were optimized. Optimization was performed with the use of central composite design (CCD). Besides electrochemical oxidation of analytes (phase I of metabolic transformation), addition of glutathione (GSH) for follow-up reactions (phase II conjunction) was also investigated. The electrochemical results were compared to in-vivo experiments by analyzing plasma and urine samples from patients who had been administered selected cardiovascular drugs. These results show that electrochemistry coupled to mass spectrometry turned out to be an analytical tool suitable to procure a feasible analytical base for the envisioned in vivo experiments.
- Experimental evidence of high pressure decoupling between charge transport and structural dynamics in a protic ionic glass-former. [Journal Article]
- SRSci Rep 2017 Aug 01; 7(1):7084
- In this paper the relaxation dynamics of ionic glass-former acebutolol hydrochloride (ACB-HCl) is studied as a function of temperature and pressure by using dynamic light scattering and broadband die...
In this paper the relaxation dynamics of ionic glass-former acebutolol hydrochloride (ACB-HCl) is studied as a function of temperature and pressure by using dynamic light scattering and broadband dielectric spectroscopy. These unique experimental data provide the first direct evidence that the decoupling between the charge transport and structural relaxation exists in proton conductors over a wide T-P thermodynamic space, with the time scale of structural relaxation being constant at the liquid-glass transition (τα = 1000 s). We demonstrate that the enhanced proton transport, being a combination of intermolecular H+ hopping between cation and anion as well as tautomerization process within amide moiety of ACB molecule, results in a breakdown of the Stokes-Einstein relation at ambient and elevated pressure with the fractional exponent k being pressure dependent. The dT g /dP coefficient, stretching exponent βKWW and dynamic modulus E a /ΔV # were found to be the same regardless of the relaxation processes studied. This is in contrast to the apparent activation volume parameter that is different when charge transport and structural dynamics are considered. These experimental results together with theoretical considerations create new ideas to design efficient proton conductors for potential electrochemical applications.
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- Determination of Some β-Blockers and β2-Agonists in Plasma and Urine Using Liquid Chromatography-tandem Mass Spectrometry and Solid Phase Extraction. [Journal Article]
- JCJ Chromatogr Sci 2017 Sep 01; 55(8):846-856
- A highly sensitive method for the determinations of acebutolol, clenbuterol, nadolol, oxprenolol, propranolol, terbutaline and timolol β-blockers and β2-agonists in plasma and urine was developed. Th...
A highly sensitive method for the determinations of acebutolol, clenbuterol, nadolol, oxprenolol, propranolol, terbutaline and timolol β-blockers and β2-agonists in plasma and urine was developed. The method was optimized using electrospray ionization liquid chromatography-tandem mass spectrometry (LC-ESI-MS-MS) and clean screen solid phase extraction cartridges. Matrix effect was reduced by removing co-extractives from the SPE cartridges using methanol prior to drugs' elution. Using blood and serum matrices for calibration and applying the internal standard method has also contributed to the reduction of matrix effect. Method's validation yielded linear dynamic ranges of 5.0-50.0 and 50.0-1000.0 ng/ml for drugs spiked in plasma and urine respectively. It also gave correlation coefficients of 0.94-0.99, detection limits ranged in 0.06-5.04 pg/ml and quantification limits ranged in 0.14-22.88 pg/ml for the target drugs. Developed method was successfully applied to the analysis of β-blockers and β2-agonists in plasma and urine samples. Plasma samples fortified with drugs at 7.5, 40.0 and 75.0 ng/ml gave percentage recoveries ranged in 78.66-118.10, 67.02-83.97 and 74.77-93.80, respectively. Urine samples fortified with drugs at 80.0, 400.0 and 800.0 ng/ml gave percentage recoveries ranged in 104.68-130.18, 110.23-125.16 and 109.46-116.89, respectively. Variance coefficients ranged in 0.05-0.35 and 0.04-0.12 were, respectively, obtained for the analyses of drugs in plasma and urine samples. Results suggest that developed method is well suited for the analysis of investigated drugs in biological fluids.