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British Journal of Clinical Pharmacology Jul 19801 The pharmacological effects and the pharmacokinetics of betaxolol (SL 75212), a new beta-adrenoceptor blocking agent, were compared with those of propranolol and a... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
1 The pharmacological effects and the pharmacokinetics of betaxolol (SL 75212), a new beta-adrenoceptor blocking agent, were compared with those of propranolol and a placebo in a double-blind trial involving six healthy volunteers. 2 Heart rate (HR), myocardial contractile force (MCF), systolic blood pressure (SBP) and peak expiratory flow rate (PEFR) were measured at rest and during vigorous exercise before and at intervals up to 25 h after oral administration of the drugs. In addition, plasma renin activity (PRA) at rest and blood levels of betaxolol and propranolol were determined. 3. Betaxolol proved to be a potent and long-lasting beta-adrenoceptor blocking drug, devoid of intrinsic beta-sympathomimetic activity. Its beta-adrenoceptor blocking action was shown to four-fold that of propranolol at the cardiac and renal levels and to last at least 25 h after drug intake. 4 The peak blood level of betaxolol was reached 2 to 4 hr after its administration, the first-pass loss is likely to be low and the half-life is 12.3 h. These pharmacokinetic data are perfectly consistent with the long duration of the pharmacological effects of betaxolol in man.
Topics: Adrenergic beta-Antagonists; Adult; Betaxolol; Blood Pressure; Double-Blind Method; Female; Heart Rate; Hemodynamics; Humans; Kinetics; Male; Myocardial Contraction; Peak Expiratory Flow Rate; Propanolamines; Propranolol; Renin
PubMed: 6104973
DOI: 10.1111/j.1365-2125.1980.tb00500.x -
International Journal of Ophthalmology 2014To demonstrate the cytotoxic effect of betaxolol and its underlying mechanism on human corneal endothelial cells (HCE cells) in vitro and cat corneal endothelial cells...
AIM
To demonstrate the cytotoxic effect of betaxolol and its underlying mechanism on human corneal endothelial cells (HCE cells) in vitro and cat corneal endothelial cells (CCE cells) in vivo, providing experimental basis for safety anti-glaucoma drug usage in clinic of ophthalmology.
METHODS
In vivo and in vitro experiments were conducted to explore whether and how betaxolol participates in corneal endothelial cell injury. The in vitro morphology, growth status, plasma membrane permeability, DNA fragmentation, and ultrastructure of HCE cells treated with 0.021875-0.28g/L betaxolol were examined by light microscope, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, acridine orange (AO)/ethidium bromide (EB) double-fluorescent staining, DNA agarose gel electrophoresis, and transmission electron microscope (TEM). The in vivo density, morphology, and ultrastructure of CCE cells, corneal thickness, and eye pressure of cat eyes treated with 0.28g/L betaxolol were investigated by specular microscopy, applanation tonometer, alizarin red staining, scanning electron microscope (SEM), and TEM.
RESULTS
Exposure to betaxolol at doses from 0.0875g/L to 2.8g/L induced morphological and ultrastructural changes of in vitro cultured HCE cells such as cytoplasmic vacuolation, cellular shrinkage, structural disorganization, chromatin condensation, and apoptotic body appearance. Simultaneously, betaxolol elevated plasma membrane permeability and induced DNA fragmentation of these cells in a dose-dependent manner in AO/EB staining. Furthermore, betaxolol at a dose of 2.8g/L also induced decrease of density of CCE cells in vivo, and non-hexagonal and shrunk apoptotic cells were also found in betaxolol-treated cat corneal endothelia.
CONCLUSION
Betaxolol has significant cytotoxicity on HCE cells in vitro by inducing apoptosis of these cells, and induced apoptosis of CCE cells in vivo as well. The findings help provide new insight into the apoptosis-inducing effect of anti-glaucoma drugs in eye clinic.
PubMed: 24634857
DOI: 10.3980/j.issn.2222-3959.2014.01.03 -
Circulation Journal : Official Journal... May 2008The aim of the study was to evaluate whether the combined treatment of calcium channel blocker, amlodipine and beta-blocker, betaxolol, favorably affects cardiac... (Comparative Study)
Comparative Study Randomized Controlled Trial
Comparative effects of amlodipine monotherapy and combination therapy with betaxolol on cardiac autonomic nervous activity and health-related quality of life in patients with poorly controlled hypertension.
BACKGROUND
The aim of the study was to evaluate whether the combined treatment of calcium channel blocker, amlodipine and beta-blocker, betaxolol, favorably affects cardiac autonomic nervous activity (CANA) and health-related quality of life (HRQL).
METHODS AND RESULTS
A total of 65 patients with a poor blood pressure (BP) control with a low dose amlodipine therapy were randomly assigned to the amlodipine dose-up group (n=21) and betaxolol adding group (n=44). Before and after a 6-month treatment, BP, heart rate variability (HRV), HRQL and blood chemistries were evaluated. Low frequency (LF) spectra/high frequency (HF) spectra and HF/total power spectra (TP) were calculated as indexes of CANA, and HRQL was assessed by the questionnaire sheets. BP was well controlled in all patients of the present study. In the betaxolol adding group, LF/HF decreased (2.1+/-1.9 to 1.3+/-0.9, p<0.05) and HF/TP reciprocally increased (0.41+/-0.17 to 0.52+/-0.18, p<0.05), whereas the amlodipine dose-up group showed no significant changes in the HRV. HRQL was significantly improved in the betaxolol adding group, whereas it remained unchanged in the amlodipine dose-up group. Blood chemistries remained unchanged except for the slightly increased plasma brain natriuretic peptide concentrations in the betaxolol adding group (36+/-47 to 62+/-62 pg/ml, p<0.05).
CONCLUSIONS
Combined treatment of amlodipine and betaxolol appears to be more useful than amlodipine dose-up therapy, because combined treatment improves CANA and HRQL.
Topics: Aged; Amlodipine; Antihypertensive Agents; Autonomic Nervous System; Betaxolol; Blood Pressure; Calcium Channel Blockers; Drug Therapy, Combination; Female; Heart; Heart Rate; Humans; Hypertension; Male; Middle Aged; Patient Satisfaction; Prospective Studies; Quality of Life; Surveys and Questionnaires
PubMed: 18441457
DOI: 10.1253/circj.72.764 -
Japanese Journal of Pharmacology Oct 1990Effects of betaxolol, a cardioselective beta-adrenoceptor antagonist, on cardiohemodynamics and coronary circulation were investigated in two kinds of anesthetized... (Comparative Study)
Comparative Study
Effects of betaxolol, a cardioselective beta-adrenoceptor antagonist, on cardiohemodynamics and coronary circulation were investigated in two kinds of anesthetized open-chest dog preparations in comparison with those of atenolol and propranolol. When administered intravenously, betaxolol, atenolol and propranolol produced dose-dependent decreases in the heart rate (HR), maximum left ventricular dP/dt [+)dP/dt), cardiac output (CO) and mean arterial pressure (MAP). Although all three drugs were almost equipotent in decreasing HR, betaxolol was much less potent than atenolol and propranolol in decreasing (+)dP/dt. Betaxolol decreased the total peripheral resistance (TPR), whereas atenolol and propranolol increased it. In another series of experiments, when administered intravenously, betaxolol, atenolol and propranolol all produced a decrease in the myocardial oxygen consumption (MVO2) and an increase in the atrioventricular conduction time (AVCT). All three drugs were nearly equipotent in decreasing MVO2, although betaxolol was less potent than the other two drugs at higher doses (greater than 300 micrograms/kg). Prolongation of AVCT with propranolol was stronger than those with betaxolol and atenolol. These results suggest that, unlike atenolol and propranolol, the decrease in TPR as well as beta 1-adrenoceptor blockade may be responsible for both the hypotensive effect of betaxolol and the decrease in MVO2 with betaxolol. The result that the cardiodepressant effect of betaxolol was much less potent than those of atenolol and propranolol suggests that betaxolol would be more beneficial than the others in the treatment of ischemic heart disease.
Topics: Animals; Atenolol; Betaxolol; Blood Pressure; Cardiac Output; Coronary Circulation; Dogs; Female; Heart; Heart Rate; Hemodynamics; Male; Propranolol
PubMed: 2077180
DOI: 10.1254/jjp.54.113 -
Asian Journal of Pharmaceutical Sciences Mar 2019Low drug loading efficiency is one of the main obstacles hindering the application of contact lenses (CLs) as the carrier for extended ocular drug delivery. Here in this...
Low drug loading efficiency is one of the main obstacles hindering the application of contact lenses (CLs) as the carrier for extended ocular drug delivery. Here in this study, a simple and effective drug loading method based on salt induced modulation was proposed and demonstrated with mechanism elucidation. First of all, using poly (2-hydroxyethyl methacrylate) (p-HEMA) as the contact lens material, betaxolol hydrochloride, Diclofenac Sodium and Betaxolol Base as the model drugs with different solubility, influence of salt concentration, salt type (sodium salts of sulfate, chloride, and sulfocyanate) and drug properties in the loading solution on drug loading efficiency was investigated. Mechanism of enhanced drug loading in contact lens was further explored via studying the influence of salt on the absorption isotherm, drug solubility and water content of CLs. Applicability of this method to other CLs materials was also investigated. It was demonstrated that adjusting the ionic strength of loading solutions resulted in significant increase of drug loading in CLs. Type and concentration of the salts and solubility of the drug were the main factors influencing enhancement ratio of drug loading. The mechanism for improved drug loading was related to the reduced drug solubility in loading solutions and the reduced bound water content in contact lenses. Modulation of drug loading by adjusting ionic strength was also applicable to other CLs and the light transmittance was not affected. This method was more suitable for salt-form drugs with high solubility. In summary, adjusting ionic strength of loading solution is an economical and effective way to improve drug loading in CLs, and this simple method may also find application in other hydrogel based drug delivery systems.
PubMed: 32104452
DOI: 10.1016/j.ajps.2018.05.002 -
Journal of Personalized Medicine Oct 2022Alzheimer's disease (AD) is a neurologic disorder causing brain atrophy and the death of brain cells. It is a progressive condition marked by cognitive and behavioral...
Alzheimer's disease (AD) is a neurologic disorder causing brain atrophy and the death of brain cells. It is a progressive condition marked by cognitive and behavioral impairment that significantly interferes with daily activities. AD symptoms develop gradually over many years and eventually become more severe, and no cure has been found yet to arrest this process. The present study is directed towards suggesting putative novel solutions and paradigms for fighting AD pathogenesis by exploiting new insights from network medicine and drug repurposing strategies. To identify new drug-AD associations, we exploited SAveRUNNER, a recently developed network-based algorithm for drug repurposing, which quantifies the vicinity of disease-associated genes to drug targets in the human interactome. We complemented the analysis with an in silico validation of the candidate compounds through a gene set enrichment analysis, aiming to determine if the modulation of the gene expression induced by the predicted drugs could be counteracted by the modulation elicited by the disease. We identified some interesting compounds belonging to the beta-blocker family, originally approved for treating hypertension, such as betaxolol, bisoprolol, and metoprolol, whose connection with a lower risk to develop Alzheimer's disease has already been observed. Moreover, our algorithm predicted multi-kinase inhibitors such as regorafenib, whose beneficial effects were recently investigated for neuroinflammation and AD pathology, and mTOR inhibitors such as sirolimus, whose modulation has been associated with AD.
PubMed: 36294870
DOI: 10.3390/jpm12101731 -
International Journal of Nanomedicine 2022Glaucoma is a chronic disease that requires long-term adherence to treatment. Topical application of conventional eye drops results in substantial drug loss due to rapid...
INTRODUCTION
Glaucoma is a chronic disease that requires long-term adherence to treatment. Topical application of conventional eye drops results in substantial drug loss due to rapid tear turnover, with poor drug bioavailability being a major challenge for efficient glaucoma treatment. We aimed to prepare the anti-glaucoma drug betaxolol hydrochloride (BH) as a novel nano-delivery system that prolonged the retention time at the ocular surface and improved bioavailability.
METHODS
We constructed multifunctional nanoparticles (MMt-BH-HA/CS-ED NPs) by ion cross-linking-solvent evaporation method. The particle size, zeta potential, encapsulation efficiency and drug loading of MMt-BH-HA/CS-ED NPs were physicochemically characterized. The structure of the preparations was characterized by microscopic techniques of SEM, TEM, XPS, XRD, FTIR and TGA, and evaluated for their in vitro release performance as well as adhesion properties. Its safety was investigated using irritation assays of hemolysis experiment, Draize test and histopathology examination. Precorneal retention was examined by in vivo fluorescence tracer method and pharmacokinetics in tear fluid was studied. A model of high IOP successfully induced by injection of compound carbomer solution was used to assess the IOP-lowering efficacy of the formulation, and it was proposed that micro-interactions between the formulation and the tear film would be used to analyze the behavior at the ocular surface.
RESULTS
The positively charged MMt-BH-HA/CS-ED NPs were successfully prepared with good two-step release properties, higher viscosity, and slower pre-corneal diffusion rate along with longer precorneal retention time compared to BH solution. The micro-interactions between nanoparticles and tear film converted the drug clearance from being controlled by fast aqueous layer turnover to slow mucin layer turnover, resulting in higher drug concentration on the ocular surface, providing more durable and stable IOP-lowering efficacy.
CONCLUSION
The novel multifunctional MMt-BH-HA/CS-ED NPs can effectively reduce IOP and are suitable for the treatment of chronic disease glaucoma.
Topics: Humans; Betaxolol; Intraocular Pressure; Nanoparticles; Glaucoma; Cornea; Particle Size; Drug Carriers
PubMed: 36506343
DOI: 10.2147/IJN.S382968 -
Transactions of the American... 1996To evaluate the ocular hypotensive efficacy and safety of a fixed combination of betaxolol (0.25%) and pilocarpine (1.75%). (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
PURPOSE
To evaluate the ocular hypotensive efficacy and safety of a fixed combination of betaxolol (0.25%) and pilocarpine (1.75%).
METHODS
Three multicenter, double-masked, parallel trials were completed in patients with primary open-angle glaucoma or ocular hypertension of 3 months' treatment duration. Studies 1 and 2 were three-arm comparisons of betaxolol, pilocarpine, and a fixed combination, each used 3 times daily. Study 3 was a two-arm study of the fixed combination with and without a surfactant, used twice daily. In all studies, there was a 1-month runin period with betaxolol 0.25% suspension given twice daily. There were 182 patients in Study 1, 186 patients in Study 2, and 166 patients in Study 3.
RESULTS
In all 3 studies, approximately 10% to 15% of patients treated with pilocarpine or the combination therapy were terminated from further participation because of typical pilocarpine side effects (eg, blurred vision, headache). In studies 1 and 2, there was a mean reduction in intraocular pressure from a betaxolol baseline of approximately 3 to 4 mmHg. Patients continuing on betaxolol alone or randomly assigned to pilocarpine alone experienced a mean reduction of 1 to 2 mm Hg. Overall, the combination was approximately 2 mmHg more effective than either betaxolol or pilocarpine alone. In Study 3, the two betaxolol combinations had equivalent efficacy.
CONCLUSION
In patients requiring more than one ocular hypotensive agent, the combination of betaxolol and pilocarpine in a single formulation appears to be an effective and relatively safe agent. The use of this combination agent promises the potential for enhanced patient convenience.
Topics: Adrenergic beta-Antagonists; Aged; Betaxolol; Double-Blind Method; Drug Therapy, Combination; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Ocular Hypertension; Ophthalmic Solutions; Parasympathomimetics; Pilocarpine; Safety; Treatment Outcome
PubMed: 8981691
DOI: No ID Found -
Journal of Pharmacological Sciences Mar 2008In the present study, we investigated the direct effects of antiglaucoma drugs (timolol, betaxolol, pilocarpine, and latanoprost) on N-methyl-D-aspartate (NMDA)-receptor...
In the present study, we investigated the direct effects of antiglaucoma drugs (timolol, betaxolol, pilocarpine, and latanoprost) on N-methyl-D-aspartate (NMDA)-receptor function using a Xenopus oocytes expression system and electrophysiological techniques. In oocytes expressing wild-type NMDA (NR1a/NR2A) receptors, timolol and betaxolol significantly inhibited glutamate-evoked currents, whereas less inhibition was obtained with pilocarpine, and latanoprost had few effects. Moreover, the effect of timolol and betaxolol was noncompetitive with respect to glutamate. Mutations that changed Asn616 of the NR1a subunit, a critical residue for Mg(2+) blocking of NMDA receptors, to Arg (N616R) or Gln (N616Q) almost eliminated the inhibitory effects of timolol and betaxolol, as well as the blocking effect of Mg(2+). Experiments were also carried out to examine the protective effects of timolol and betaxolol against death of oocytes expressing NMDA receptors. During incubation of oocytes, especially in Mg(2+)-free medium, cell death was induced by addition of glutamate because of the continuous activation of the NMDA receptors expressed. Timolol and betaxolol significantly improved oocyte viability when they were added during the incubation period. These results suggest that timolol and betaxolol may have an additional role that they directly inhibit NMDA-receptor function, possibly via N616 of the NR1a subunit.
Topics: Adrenergic beta-Antagonists; Animals; Betaxolol; Calcium; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists; Female; Glaucoma; Magnesium; Receptors, N-Methyl-D-Aspartate; Timolol; Xenopus laevis
PubMed: 18319565
DOI: 10.1254/jphs.fp0071776 -
Molecules (Basel, Switzerland) Mar 2022Beta adrenoblockers are a large class of drugs used to treat cardiovascular diseases, migraines, glaucoma and hyperthyroidism. Over the last couple of decades, the...
Beta adrenoblockers are a large class of drugs used to treat cardiovascular diseases, migraines, glaucoma and hyperthyroidism. Over the last couple of decades, the anticancer effects of these compounds have been extensively studied. However, the exact mechanism is still not known, and more detailed studies are required. The aim of our study was to evaluate the anticancer activity of beta adrenoblockers in non-small cell lung cancer cell lines A549 and H1299. In order to find the relationship with their selectivity to beta adrenoreceptors, selective (atenolol, betaxolol, esmolol, metoprolol) and non-selective (pindolol, propranolol and timolol) beta blockers were tested. The effect on cell viability was evaluated by MTT assay, and the activity on cell ability to form colonies was tested by clonogenic assay. The type of cell death was evaluated by cell double staining with Hoechst 33342 and Propidium iodide. The most active adrenoblockers against both tested cancer cell lines were propranolol and betaxolol. They completely inhibited lung cancer cell colony formation at 90% of the EC (half-maximal effective concentration) value. Most tested compounds induced cell death through apoptosis and necrosis. There was no correlation established between beta adrenoblocker anticancer activity and their selectivity to beta adrenoreceptors.
Topics: Adrenergic beta-Antagonists; Carcinoma, Non-Small-Cell Lung; Cell Line; Humans; Lung Neoplasms; Propranolol
PubMed: 35335303
DOI: 10.3390/molecules27061938