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Spectrochimica Acta. Part A, Molecular... Jul 2023In this work, a label-free, rapid, and sensitive synchronous spectrofluorometric method was implemented to assay atenolol (ATL) and ivabradine hydrochloride (IVB) in...
In this work, a label-free, rapid, and sensitive synchronous spectrofluorometric method was implemented to assay atenolol (ATL) and ivabradine hydrochloride (IVB) in pharmaceutical and biological matrices. Simultaneous determination of ATL and IVB by conventional spectrofluorometry cannot be implemented because of the clear overlap of the emmision spectra of ATL and IVB. To overcome this problem, synchronous fluorescence measurements at a constant wavelength difference (Δλ) combined with mathematical derivatization of the zero order spectra were perforemed. The results indicated a good resolution between emission spectra of the studied drugs when the first-order derivative of the synchronous fluorescence scans at Δλ = 40 nm was conducted using ethanol as the optimum solvent which is less hazardous than other organic solvents such as methanol and acetonitrile, keeping the method safe and green. The amplitudes of the first derivative synchronous fluorescent scans of ATL and IVB in ethanol were monitored at 286 and 270 nm to simultaneously estimate ATL and IVB, respectively. Method optimisation was conducted by assessing different solvents, buffer pHs, and surfactants. The optimum results were obtained when ethanol was utilized as a solvent without using any other additives. The developed method was linear over concentration ranges of 10.0-250.0 ng mL for IVB and 100.0-800.0 ng mL for ATL with detection limits of 3.07 and 26.49 ng mL for IVB and ATL, respectively. The method was utilized to assay the studied drugs in their dosages and in human urine samples with acceptable % recoveries and RSD values. The greenness of the method was implemented by three approaches involving the recently reported metric (AGREE) which ensured the eco-freindship and safety of the method.
Topics: Humans; Atenolol; Ivabradine; Solvents; Ethanol; Spectrometry, Fluorescence; Pharmaceutical Preparations
PubMed: 36940537
DOI: 10.1016/j.saa.2023.122626 -
Annals of Translational Medicine Jan 2021Infantile hemangiomas (IHs) are the most frequently occurring pediatric lesions. Oral propranolol has been shown to be safe and effective in infants with IHs. Side...
BACKGROUND
Infantile hemangiomas (IHs) are the most frequently occurring pediatric lesions. Oral propranolol has been shown to be safe and effective in infants with IHs. Side effects such as sleep disturbances have been associated with propranolol. Atenolol is a hydrophilic, selective β1-blocker and therefore may be not associated with side effects attributable to β2-adrenergic receptor blockade and lipophilicity. However, the efficacy of atenolol in the treatment of IHs is poorly understood. The aim of this study was to evaluate the efficacy of atenolol in the treatment of proliferating IHs in a clinical cohort including 133 consecutive patients.
METHODS
In this study, we enrolled 133 patients diagnosed as proliferating IHs from the routine clinical and referral practices of the authors. The procedures followed were in accordance with the ethical standards of the Institute Review Board of Shanghai Ninth People's Hospital and Helsinki Declaration. Clinical characteristics, including demographic data and clinical morphology, were collated. Responses to oral atenolol therapy were graded as: excellent, good, fair and poor. According to the reaction to atenolol treatment, additional medications or therapy were used for IH patients to achieve satisfactory clinical results.
RESULTS
In this study, 128 (96.2%) of 133 IH patients responded to oral atenolol, and the response rate (RR) was significantly different for different ages of patients (P<0.05), with the youngest patients having the highest RR. The mean time of treatment was 4.9 months. Forty-one patients who exhibited residual hyperpigmentation or telangiectasia were further treated with timolol maleate cream (n=32) or pulsed dye laser (n=9). All the 41 patients showed positive response. No life-threatening complications were noted during and after oral atenolol. Only 4 (3.0%) of 133 patients developed minor complications including diarrhea. No agitation and bronchospasm were noted in our study.
CONCLUSIONS
This study demonstrated that atenolol was effective in the treatment of IHs. Compared to propranolol, atenolol seems to have a similar effect on IHs. Furthermore, atenolol seems to be less frequently associated with potentially life-threatening side effects.
PubMed: 33569418
DOI: 10.21037/atm-20-5359 -
Drug Research Apr 2020Propranolol and atenolol are known as β receptor blocker drugs. These drugs are used to treat some heart diseases. There are controversies in the relationship between...
Propranolol and atenolol are known as β receptor blocker drugs. These drugs are used to treat some heart diseases. There are controversies in the relationship between the use of beta-blocker drugs and the level of reactive oxygen species (ROS). Mitochondria as one of the most important sources of ROS are considered as one of the targets of drug-induced cardiotoxicity. The aim of this study was to evaluate the effects of propranolol and atenolol on mitochondria isolated from the heart. To achieve this aim, several markers of mitochondrial and cellular toxicity were evaluated. The key results of this study are the increased ROS level, collapse in mitochondrial membrane potential (MMP), mitochondrial swelling and cytochrome c release as well as disruption of respiratory chain complex II in mitochondria in isolated heart mitochondria after exposure to propranolol and atenolol. The results indicate an increase in caspase-3 activity and a decrease in the ATP level in cardiomyocytes after exposure to propranolol and atenolol. The underlying mechanisms of propranolol and atenolol induced cardiotoxicity may be associated with alterations in mitochondrial function, oxidative stress, and changes in the mitochondrial membrane.
Topics: Adrenergic beta-Antagonists; Animals; Apoptosis; Atenolol; Cytochromes c; Electron Transport Complex II; Male; Membrane Potential, Mitochondrial; Mitochondria, Heart; Mitochondrial Membranes; Mitochondrial Swelling; Oxidative Stress; Propranolol; Rats; Reactive Oxygen Species; Toxicity Tests, Acute
PubMed: 32120430
DOI: 10.1055/a-1112-7032 -
AAPS PharmSciTech Nov 2021An important challenge to overcome in the solid dosage forms technology is the selection of the most biopharmaceutically efficient polymeric excipients. The excipients...
An important challenge to overcome in the solid dosage forms technology is the selection of the most biopharmaceutically efficient polymeric excipients. The excipients can be selected, among others, by compatibility studies since incompatibilities between ingredients of the drug formulations adversely affect their bioavailability, stability, efficacy, and safety. Therefore, new, fast, and reliable methods for detecting incompatibility are constantly being sought. Hence, the purpose of this work was to assess the usefulness of a heating, cooling, and reheating differential scanning calorimetry (DSC) program for detecting potential incompatibilities between atenolol, an active pharmaceutical ingredient (API), and polymeric excipients. Hot-stage microscopy (HSM), Fourier transform infrared (FTIR) spectroscopy, and powder X-ray diffraction (PXRD) were used as supporting techniques. Additionally, principal component analysis (PCA) and hierarchical cluster analysis (HCA) served as tools to support the interpretation of the data acquired from the DSC curves and FTIR spectra. As the alterations in the shape of the DSC peak of atenolol which are indicative of incompatibility are visible only on the cooling and reheating curves of the mixtures, the DSC heating-cooling-reheating program was found to be very useful for identifying potential incompatibilities in the binary mixtures of atenolol and polymeric excipients. The melting and recrystallization of atenolol alone and in its mixtures were also confirmed by HSM, while FTIR displayed changes in the spectra of mixtures due to incompatibility. These studies revealed that atenolol is incompatible with hydroxyethylcellulose, hypromellose, and methylcellulose. PXRD measurements at room temperature revealed that the crystallinity of atenolol did not change in these mixtures. However, its crystallinity was reduced in the mixtures previously heated up to 155 °C and then cooled to 25 °C.
Topics: Atenolol; Calorimetry, Differential Scanning; Cluster Analysis; Excipients; Principal Component Analysis; Spectroscopy, Fourier Transform Infrared
PubMed: 34799781
DOI: 10.1208/s12249-021-02143-2 -
Environmental Research Nov 2022β-blockers are widely used chiral pharmaceuticals to treat hypertension and cardiovascular diseases, which are ubiquitously detected in the water-soil environment....
β-blockers are widely used chiral pharmaceuticals to treat hypertension and cardiovascular diseases, which are ubiquitously detected in the water-soil environment. However, little is known about their biogeochemical behaviors and enantiomer selectivity during soil migration and transformation. In this study, the adsorption and leaching behaviors of β-blockers in fluvo-aquic soil and black soil were investigated. The adsorption of β-blockers was fit well by the Freundlich adsorption isotherm (R > 0.913) and the adsorption affinity of β-blockers decreased in the following order: propranolol (logarithm of Freundlich adsorption coefficient log K = 1.46-2.55) > atenolol (log K = 0.53-1.04) > sotalol (log K = 0.32-1.01). An increase in ionic strength and dissolved organic matter (DOM) inhibited their soil adsorption. Ionic change is the main driving force for adsorption. Besides, hydrophobic partitioning and hydrogen bonding played key roles in the adsorption of propranolol and atenolol, respectively. The leaching behaviors of β-blockers are related to their hydrophobicity. An increase in ionic strength enhanced the migration of β-blockers to deeper soil layers, and the presence of DOM accelerated the migration of sotalol and propranolol. The migration potential of β-blockers in black soil is lower than that in fluvo-aquic soil, which could be ascribed to the higher organic matter content and strong ion exchange ability of black soil. Further, more significant enantiomer selectivity of β-blockers was found in black soil (e.g. enantiomer fraction of atenolol = 0.61) than in fluvo-aquic soil (e.g. enantiomer fraction of atenolol = 0.53) during the leaching process. The microbial activity might influence the enantiomer selectivity of studied β-blockers during soil leaching.
Topics: Adsorption; Atenolol; Propranolol; Soil; Soil Pollutants; Sotalol
PubMed: 35961549
DOI: 10.1016/j.envres.2022.114062 -
Spectrochimica Acta. Part A, Molecular... Nov 2019Geometry optimization of atenolol (ATN) in the gas phase was carried out using B3LYP-D3BJ/6-31++G(d,p), CAM-B3LYP/6-31++G(d,p) and M06-2X/6-31++G(d,p) levels of DFT. The...
Geometry optimization of atenolol (ATN) in the gas phase was carried out using B3LYP-D3BJ/6-31++G(d,p), CAM-B3LYP/6-31++G(d,p) and M06-2X/6-31++G(d,p) levels of DFT. The computed structural parameters were compared with the data obtained by single crystal X-ray diffraction experiment. Chemical reactivity (electronegativity, electrophilicity, hardness, chemical softness and chemical potential) was predicted with the help of HOMO- LUMO energy values. Experimental FT-IR was recorded and the calculated values were also analyzed using the same level of DFT. A complete vibrational spectrum was made to analyze the potential energy distribution (PED). Stability of the molecule arising from hyperconjugative interaction was analyzed by the natural bond orbital (NBO) analysis. The molecular electrostatic potential map was used to detect the possible electrophilic and nucleophilic sites in ATN molecule. Cocrystallization of atenolol-hydrochlorothiazide (ATN-HCTZ) was performed and the structure was analyzed by powder X-ray diffraction. NBO analysis was carried out on the ATN-HCTZ cocrystal for the elucidation of inter and intra-molecular hydrogen bonding interactions in the structure. Atenolol interaction with human serum albumin (HSA) was investigated by a molecular docking study.
Topics: Adrenergic beta-1 Receptor Antagonists; Antihypertensive Agents; Atenolol; Crystallization; Crystallography, X-Ray; Density Functional Theory; Hydrochlorothiazide; Models, Molecular; Molecular Conformation; Static Electricity
PubMed: 31176161
DOI: 10.1016/j.saa.2019.117200 -
The New England Journal of Medicine Nov 2014
Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Aorta; Aortic Aneurysm; Atenolol; Female; Humans; Losartan; Male; Marfan Syndrome
PubMed: 25405389
DOI: 10.1056/NEJMe1412950 -
The Journal of Clinical Investigation Feb 2022Propranolol and atenolol, current therapies for problematic infantile hemangioma (IH), are composed of R(+) and S(-) enantiomers: the R(+) enantiomer is largely devoid...
Propranolol and atenolol, current therapies for problematic infantile hemangioma (IH), are composed of R(+) and S(-) enantiomers: the R(+) enantiomer is largely devoid of beta blocker activity. We investigated the effect of R(+) enantiomers of propranolol and atenolol on the formation of IH-like blood vessels from hemangioma stem cells (HemSCs) in a murine xenograft model. Both R(+) enantiomers inhibited HemSC vessel formation in vivo. In vitro, similar to R(+) propranolol, both atenolol and its R(+) enantiomer inhibited HemSC to endothelial cell differentiation. As our previous work implicated the transcription factor sex-determining region Y (SRY) box transcription factor 18 (SOX18) in propranolol-mediated inhibition of HemSC to endothelial differentiation, we tested in parallel a known SOX18 small-molecule inhibitor (Sm4) and show that this compound inhibited HemSC vessel formation in vivo with efficacy similar to that seen with the R(+) enantiomers. We next examined how R(+) propranolol alters SOX18 transcriptional activity. Using a suite of biochemical, biophysical, and quantitative molecular imaging assays, we show that R(+) propranolol directly interfered with SOX18 target gene trans-activation, disrupted SOX18-chromatin binding dynamics, and reduced SOX18 dimer formation. We propose that the R(+) enantiomers of widely used beta blockers could be repurposed to increase the efficiency of current IH treatment and lower adverse associated side effects.
Topics: Animals; Atenolol; Hemangioma; Humans; Mice; Neoplastic Stem Cells; Neovascularization, Pathologic; Propranolol; Xenograft Model Antitumor Assays
PubMed: 34874911
DOI: 10.1172/JCI151109 -
Journal of Cardiothoracic and Vascular... Aug 2016To evaluate the protective effects of preinjury atenolol (acute v chronic) on apoptosis, contractility, oxidative stress, and inflammatory markers in...
OBJECTIVE
To evaluate the protective effects of preinjury atenolol (acute v chronic) on apoptosis, contractility, oxidative stress, and inflammatory markers in hypercholesterolemic rats undergoing intestinal ischemia-reperfusion (I/R) injury.
DESIGN
Prospective, experimental animal study.
SETTING
University laboratory.
PARTICIPANTS
Male Wistar rats (n = 32).
INTERVENTIONS
Rats were divided into the following 4 groups: 1 group was fed a normal diet (ND) (group ND+NoAT [no atenolol]), and the other 3 groups were fed a high-cholesterol diet (HCD)-group HCD+NoAT, group HCD+ChAT (chronic atenolol, 3 mg/kg/day for 8 weeks), and group HCD+AcAT (acute atenolol, 1.5 mg/kg, given 5 minutes before intestinal clamping). All rats underwent I/R injury. The superior mesenteric artery was clamped for 60 minutes, then opened for 120 minutes (reperfusion). Apoptotic cells and stimulated contractions of ileal segments were examined. Tissue markers of intestinal I/R injury were examined. Intestinal malondialdehyde, superoxide dismutase, and nitrate/nitrite levels were measured.
MEASUREMENTS AND MAIN RESULTS
The chronic atenolol group had fewer apoptotic cells and higher superoxide dismutase activity compared with the other groups. Intestinal contraction was higher in both atenolol pretreatment groups compared with the NoAT groups. Chronic and acute atenolol resulted in lower ileal levels of malondialdehyde and immunolabeling-positive cells (intestinal inducible nitric oxide synthase, endothelial nitric oxide synthase, interleukin-1, and interleukin-8) after I/R injury compared with the no atenolol groups.
CONCLUSIONS
Both chronic and acute pre-I/R injury treatment with atenolol attenuated I/R injury in this hypercholesterolemic rat model. These findings should encourage future studies of atenolol in hypercholesterolemic patients undergoing procedures with a high risk of intestinal ischemia.
Topics: Adrenergic beta-1 Receptor Antagonists; Animals; Apoptosis; Atenolol; Disease Models, Animal; Hypercholesterolemia; Inflammation; Intestines; Male; Oxidative Stress; Rats; Rats, Wistar; Reperfusion Injury
PubMed: 27521968
DOI: 10.1053/j.jvca.2016.03.140 -
Scientific Reports Jan 2016Metformin can induce breast cancer (BC) cell apoptosis and reduce BC local and metastatic growth in preclinical models. Since Metformin is frequently used along with...
Metformin can induce breast cancer (BC) cell apoptosis and reduce BC local and metastatic growth in preclinical models. Since Metformin is frequently used along with Aspirin or beta-blockers, we investigated the effect of Metformin, Aspirin and the beta-blocker Atenolol in several BC models. In vitro, Aspirin synergized with Metformin in inducing apoptosis of triple negative and endocrine-sensitive BC cells, and in activating AMPK in BC and in white adipose tissue (WAT) progenitors known to cooperate to BC progression. Both Aspirin and Atenolol added to the inhibitory effect of Metformin against complex I of the respiratory chain. In both immune-deficient and immune-competent preclinical models, Atenolol increased Metformin activity against angiogenesis, local and metastatic growth of HER2+ and triple negative BC. Aspirin increased the activity of Metformin only in immune-competent HER2+ BC models. Both Aspirin and Atenolol, when added to Metformin, significantly reduced the endothelial cell component of tumor vessels, whereas pericytes were reduced by the addition of Atenolol but not by the addition of Aspirin. Our data indicate that the addition of Aspirin or of Atenolol to Metformin might be beneficial for BC control, and that this activity is likely due to effects on both BC and microenvironment cells.
Topics: AMP-Activated Protein Kinases; Adipose Tissue, White; Animals; Antineoplastic Agents; Apoptosis; Aspirin; Atenolol; Biomarkers, Tumor; Breast Neoplasms; Cell Line, Tumor; Disease Models, Animal; Drug Synergism; Electron Transport Complex I; Female; Humans; Metformin; NAD; Neoplasm Metastasis; Stem Cells; Triple Negative Breast Neoplasms; Tumor Burden; Tumor Microenvironment; Xenograft Model Antitumor Assays
PubMed: 26728433
DOI: 10.1038/srep18673