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Mirabegron

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https://www.readbyqxmd.com/read/28715189/diamine-tethered-bis-thiourea-organocatalyst-for-asymmetric-henry-reaction
#1
Jan Otevrel, Pavel Bobal
We have developed a novel multifunctional C2-symmetric biphenyl-based diamine-tethered bis(thiourea) organocatalyst, which was tested in the asymmetric Henry reaction. Under thoroughly optimized conditions, the catalyst provided exceptionally high yields and excellent enantioselectivities especially for electron-deficient aromatic and heterocyclic substrates. Due to high affinity of the catalyst to silica gel, a simple chromatography-free nitroaldol isolation procedure was feasible. Preliminary kinetic and spectroscopic experiments were performed in order to complete the mechanistic picture of the organocatalyzed nitroaldolisation process...
July 17, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28705713/sn003-a-crf1-receptor-antagonist-attenuates-depressive-like-behavior-and-detrusor-overactivity-symptoms-induced-by-13-cis-retinoic-acid-in-rats
#2
Andrzej Wróbel, Urszula Doboszewska, Ewa Rechberger, Piotr Wlaź, Tomasz Rechberger
Overactive bladder (OAB) often co-exists with depression in women. The corticotropin-releasing factor (CRF) system participates in the pathophysiology of both disorders. Therefore, we tested the effects of acute treatment with a reversible CRF receptor type-1 (CRF1) antagonist, SN003 (1mg/kg, i.v.), representatives of first (solifenacin, 0.03mg/kg, i.v.) and second (mirabegron, 1mg/kg, i.v.) line treatments for OAB as well as an antidepressant imipramine (30mg/kg, i.p.) on changes in behavior and detrusor overactivity (DO) symptoms induced by a 6-week administration of 13-cis-retinoic acid (13-cis-RA, 1mg/kg/day, i...
July 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28704584/patient-reported-outcomes-from-synergy-a-randomized-double-blind-multicenter-study-evaluating-combinations-of-mirabegron-and-solifenacin-compared-with-monotherapy-and-placebo-in-oab-patients
#3
Dudley Robinson, Con Kelleher, David Staskin, Elizabeth R Mueller, Christian Falconer, Jianye Wang, Arwin Ridder, Matthias Stoelzel, Asha Paireddy, Rob van Maanen, Zalmai Hakimi, Sender Herschorn
AIMS: To evaluate patient-reported outcomes (PROs) of combinations of solifenacin and mirabegron compared with solifenacin and mirabegron monotherapy and with placebo in patients with overactive bladder (OAB) from the SYNERGY trial. METHODS: Following a 4-week placebo run-in, period patients (≥18 years) with OAB were randomized 2:2:1:1:1:1 to receive solifenacin 5 mg + mirabegron 25 mg (combination 5 + 25 mg), solifenacin 5 mg + mirabegron 50 mg, (combination 5 + 50 mg), solifenacin 5 mg, mirabegron 25 mg, mirabegron 50 mg or placebo for 12 weeks, followed by a 2-week washout period...
July 13, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/28695920/pharmacology-cardiovascular-effects-of-mirabegron
#4
Karl-Erik Andersson
No abstract text is available yet for this article.
July 11, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28681036/additional-low-dose-antimuscarinics-can-improve-overactive-bladder-symptoms-in-patients-with-suboptimal-response-to-beta-3-agonist-monotherapy
#5
Jung Hyun Shin, Aram Kim, Myung-Soo Choo
PURPOSE: We aimed to assess the patient-reported outcome (PRO) and efficacy of add-on low-dose antimuscarinic therapy in over-active bladder (OAB) patients with suboptimal response to 4-week treatment with beta 3 agonist monotherapy (mirabegron, 50 mg). MATERIALS AND METHODS: We enrolled OAB patients with 4-week mirabegron (50 mg) treatment if the patients' symptoms improved, but not to a satisfactory extent (patient perception of bladder condition [PPBC] ≥4)...
July 2017: Investigative and Clinical Urology
https://www.readbyqxmd.com/read/28673067/expected-next-generation-drugs-under-development-in-relation-to-voiding-symptoms
#6
REVIEW
Kyung Jin Chung, Benjamin I Chung
New drug development is a high-risk venture, but if successful, will bring great revenues to those willing to accept the risk. In the field of urology, in particular for lower urinary tract symptoms (LUTS), the recent successful landing of drugs (e.g., mirabegron, botulinum toxin A, and tadalafil) has resulted in increased interest in new drug development. Benign prostatic hyperplasia and overactive bladder syndrome, representative LUTS diseases, are attractive targets because of their prevalence and market size in the field of urology...
June 2017: International Neurourology Journal
https://www.readbyqxmd.com/read/28670786/comparative-assessment-of-efficacy-of-onabotulinumtoxina-and-oral-therapies-anticholinergics-and-mirabegron-for-overactive-bladder-a-systematic-review-and-network-meta-analysis
#7
REVIEW
Marcus J Drake, Victor W Nitti, David A Ginsberg, Benjamin M Brucker, Zsolt Hepp, Rachael McCool, Julie M Glanville, Kelly Fleetwood, Daniel James, Christopher R Chapple
OBJECTIVES: To compare the efficacy of onabotulinumtoxinA, mirabegron, and anticholinergics in adults with idiopathic overactive bladder (OAB) using network meta-analysis (NMA). SUBJECTS AND METHODS: Information sources were searched for randomized blinded controlled trials, of at least 2 weeks duration, comparing any dose of onabotulinumtoxinA, eligible oral/transdermal anticholinergics, or mirabegron, with each other or placebo, in adults with OAB. Bayesian random-effects models were used to synthesize the results at week 12: NMA for responder analyses and network meta-regression (NMR) for change from baseline analyses...
July 3, 2017: BJU International
https://www.readbyqxmd.com/read/28646416/assessing-preference-based-outcome-measures-for-overactive-bladder-an-evaluation-of-patient-reported-outcome-data-from-the-beside-clinical-trial
#8
REVIEW
Mike Herdman, Jameel Nazir, Zalmai Hakimi, Emad Siddiqui, Moses Huang, Marco Pavesi, Scott MacDiarmid, Marcus J Drake, Nancy Devlin
OBJECTIVES: The aim of this study was to compare outcomes using two preference-based measures of health status (EQ-5D-5L and OAB-5D) in patients with overactive bladder (OAB) treated with solifenacin plus mirabegron or solifenacin monotherapy in the BESIDE trial. METHODS: Patients with OAB who remained incontinent after 4 weeks' treatment with solifenacin 5 mg were randomized 1:1:1 to combination treatment (solifenacin 5 mg plus mirabegron [25 mg for the first 4 weeks/50 mg for the last 8 weeks]), solifenacin 5 mg, or solifenacin 10 mg...
June 23, 2017: Patient
https://www.readbyqxmd.com/read/28621388/first-direct-isolation-of-stable-%C3%AE-form-crystals-of-mirabegron-a-selective-%C3%AE-3-adrenoceptor-agonist
#9
G Dattatray Deshmukh, N Mukund Bangal, C Anil Mali, J Vijay Medhane, T Vijayavitthal Mathad
An efficient and scalable method for the direct isolation of stable α-form crystals of Mirabegron (1) is developed. The developed method negates transformation of metastable β-form crystals into α-form crystals thereby overcoming the limitations of reported methods and avoids additional processing steps during its manufacture. The developed method directly provides stable α-form crystals of Mirabegron (1) with yield of around 84% and purity of >99.77% by HPLC in a single step.
June 2017: Acta Chimica Slovenica
https://www.readbyqxmd.com/read/28620791/a-prospective-double-blind-randomized-two-period-crossover-multicenter-study-to-evaluate-tolerability-and-patient-preference-between-mirabegron-and-tolterodine-in-patients-with-overactive-bladder-prefer-study
#10
David Staskin, Sender Herschorn, Jonathan Fialkov, Le Mai Tu, Terry Walsh, Carol R Schermer
INTRODUCTION AND HYPOTHESIS: The objective of this study was to assess the tolerability and treatment preference in patients with overactive bladder (OAB) treated with mirabegron or tolterodine. METHODS: This was a two-period, 8-week crossover, double-blind, phase IV study (PREFER; NCT02138747) in treatment-naive adults with OAB for 3 months or longer randomized to one of four treatment sequences in a 5:5:1:1 ratio (mirabegron/tolterodine, tolterodine/mirabegron, mirabegron/mirabegron, or tolterodine/tolterodine), separated by a washout period of 2 weeks...
June 15, 2017: International Urogynecology Journal
https://www.readbyqxmd.com/read/28618007/an-exploratory-study-in-healthy-male-subjects-of-the-mechanism-of-mirabegron-induced-cardiovascular-effects
#11
Marcel van Gelderen, Matthias Stölzel, John Meijer, Virginie Kerbusch, Christiane Collins, Cees Korstanje
To explore the role of β1 -adrenoceptors (ARs) in the heart rate response to the selective β3 -adrenoceptor agonist mirabegron, 12 young male volunteers received single oral doses of the nonselective β1/2 -AR antagonist propranolol (160 mg), the selective β1 -AR antagonist bisoprolol (10 mg), or placebo on days 1 and 5 of each period in a 3-period crossover study. On day 5, dosing was followed by a supratherapeutic dose of mirabegron (200 mg). Vital signs, impedance cardiography, and plasma renin activity were collected...
June 15, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28588652/efficacy-and-safety-of-daily-mirabegron-50-mg-in-male-patients-with-overactive-bladder-a-critical-analysis-of-five-phase-iii-studies
#12
Andrea Tubaro, José E Batista, Victor W Nitti, Sender Herschorn, Christopher R Chapple, Mary Beth Blauwet, Emad Siddiqui, Moses Huang, Matthias Oelke
BACKGROUND: Oral pharmacotherapies to treat overactive bladder (OAB) are used less in men despite a similar prevalence of storage symptoms as women. The efficacy and safety of once-daily mirabegron 50 mg was evaluated in male OAB patients from five phase III studies that included placebo or antimuscarinic (tolterodine ER 4 mg or solifenacin 5 mg) as a comparator. METHODS: Three pooled 12-week placebo-controlled studies (mirabegron 50 mg versus placebo) and one 12-week non-inferiority phase IIIb study (BEYOND; mirabegron 50 mg versus solifenacin 5 mg) were used for efficacy (daily micturition frequency, urgency and incontinence episodes) and safety analyses...
December 2017: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/28574581/the-%C3%AE-3-adrenoceptor-agonist-mirabegron-increases-human-atrial-force-through-%C3%AE-1-adrenoceptors-an-indirect-mechanism
#13
Weilan Mo, Martin C Michel, Xiang Wen Lee, Alberto J Kaumann, Peter Molenaar
BACKGROUND AND PURPOSE: Mirabegron has been classified as a β3 -adrenoceptor agonist approved for overactive bladder syndrome. We investigated possible cardiac effects of mirabegron in the absence or presence of β-adrenoceptor subtype antagonists. In view of its phenylethanolamine structure we investigated whether mirabegron has indirect sympathomimetic activity by using neuronal uptake blockers. EXPERIMENTAL APPROACH: Right atrial trabeculae, from non-failing hearts, were paced and contractile force measured at 37°C...
June 2, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28515812/cost-effectiveness-of-mirabegron-compared-to-tolterodine-er-4-mg-for-overactive-bladder-in-canada
#14
Sender Herschorn, Jameel Nazir, Barbara Ramos, Zalmai Hakimi
INTRODUCTION: This analysis compared the cost-effectiveness of once-daily regimens of mirabegron 50 mg and generic tolterodine ER 4 mg in a hypothetical cohort of previously treated patients with overactive bladder (OAB) in Canada. METHODS: A Markov model was developed to represent different health states according to OAB symptoms (frequency, incontinence), presence/absence of adverse events (AEs; dry mouth, constipation, blurred vision), and treatment status (on-treatment, discontinue treatment, restart previous treatment)...
March 2017: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/28487215/micturition-dysfunction-in-four-month-old-ovariectomized-rats-effects-of-testosterone-replacement
#15
Sandra M Bonilla-Becerra, Mariana G de Oliveira, Fabiano B Calmasini, Julio A Rojas-Moscoso, Angelina Zanesco, Edson Antunes
AIMS: Androgen deficiency has been implicated in urological complications of postmenopausal women. This study examined the effects of testosterone replacements on the lower urinary tract dysfunction in 4-month old ovariectomized (OVX) rats. MAIN METHODS: Sprague-Dawley female rats were OVX bilaterally. Three months later, rats received single intramuscular injections of testosterone undecanoate. Cystometric study, and bladder and urethra smooth muscle reactivities were evaluated...
June 15, 2017: Life Sciences
https://www.readbyqxmd.com/read/28478755/-mirabegron-a-breakthrough-in-overactive-bladder-syndrome
#16
Almudena Maestro Nombela, María José Almodóvar Carretón, Virginia Saavedra Quirós, Carlos Barreda Velázquez, Lucía Jamart Sánchez
Overactive bladder syndrome is a condition with high prevalence, which has a negative impact on patients' quality of life. A drug with a novel mechanism of action has been recently approved: mirabegron. The objective of this study is to review the scientific evidence available on mirabegron, with the aim to analyze its efficacy, safety and cost, and thus estimate its role within current pharmacotherapy. Methods: The effectiveness and safety of mirabegron were analyzed through an evaluation of scientific evidence...
May 1, 2017: Farmacia Hospitalaria
https://www.readbyqxmd.com/read/28458369/evaluation-of-maltose-induced-chemical-degradation-at-the-interface-of-bilayer-tablets
#17
Naoya Matsuzaki, Yousuke Yamamoto, Daisuke Murayama, Yoshifumi Katakawa, Hisashi Mimura, Shin-Ichiro Kimura, Yasunori Iwao, Shigeru Itai
Fixed dose combination tablets consisting of mirabegron (MB) and solifenacin succinate (SS) were developed and formulated into bilayer tablets in the current study. The results of a chemical stability study showed that the original formulation for the tablets led to a significant increase of unknown degradants in the SS layer. Two compatibility studies were conducted to simulate the interface between the MB and SS layers, and the results revealed that the degradants only formed in the presence of both active pharmaceutical ingredients (APIs), and that the presence of maltose in the SS layer was critical to inducing degradation...
2017: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28446460/inhibition-of-cholinergic-neurotransmission-by-%C3%AE-3-adrenoceptors-depends-on-adenosine-release-and-a1-receptors-activation-in-human-and-rat-urinary-bladders
#18
Isabel Silva, Ana Filipa Costa, Sílvia Moreira, Fátima Ferreirinha, Maria Teresa Magalhães-Cardoso, Isabel Calejo, Miguel Silva-Ramos, Paulo Correia-de-Sá
The direct detrusor relaxant effect of β3-adrenoceptor agonists as a primary mechanism to improve overactive bladder symptoms has been questioned. Among other targets, activation of β3-adrenoceptors down-modulate nerve-evoked acetylcholine (ACh) release, but there is insufficient evidence for the presence of these receptors on bladder cholinergic nerve terminals. Our hypothesis is that adenosine formed from the catabolism of cyclic AMP in the detrusor may act as a retrograde messenger via prejunctional A1 receptors to explain inhibition of cholinergic activity by β3-adrenoceptors...
April 26, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28436145/comparisons-of-the-clinical-outcomes-and-urodynamic-effects-of-mirabegron-versus-tolterodine-treatment-for-female-overactive-bladder-syndrome-a-subgroup-analysis-of-a-controlled-randomised-prospective-study
#19
Sheng-Mou Hsiao, Ting-Chen Chang, Chi-Hau Chen, Wen-Yih Wu, Ho-Hsiung Lin
OBJECTIVES: The impact of mirabegron on clinical outcome and urodynamic parameters may be important for clinical practice. Thus, the aim of this study was to compare the clinical outcomes and urodynamic effects of mirabegron (Betmiga 50 mg) versus tolterodine (Detrusitol ER 4 mg) treatment for women with overactive bladder syndrome (OAB). METHODS: Women with OAB were randomized to receive 12 weeks of mirabegron 50 mg, tolterodine extended-release 4 mg or placebo treatment...
April 23, 2017: Lower Urinary Tract Symptoms
https://www.readbyqxmd.com/read/28434969/translational-science-approach-for-assessment-of-cardiovascular-effects-and-proarrhythmogenic-potential-of-the-beta-3-adrenergic-agonist-mirabegron
#20
Cees Korstanje, Masanori Suzuki, Koichiro Yuno, Shuichi Sato, Masashi Ukai, Marlowe J Schneidkraut, Gan X Yan
INTRODUCTION: Translational assessment of cardiac safety parameters is a challenge in clinical development of beta-3 adrenoceptor agonists. The preclinical tools are presented that were used for assessing human safety for mirabegron. METHODS: Studies were performed on electrical conductance at ion channels responsible for cardiac repolarization (IKr, IKs, Ito, INa, and ICa,L), on QT-interval, subendocardial APD90, Tpeak-end interval, and arrhythmia's in ventricular dog wedge tissue in vitro and on cardiovascular function (BP, HR, and QTc) in conscious dogs...
April 20, 2017: Journal of Pharmacological and Toxicological Methods
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