Urology reports (St. - Petersburg)Urology reports (St. - Petersburg)Урологические ведомостиUrology reports (St. - Petersburg)2225-90742687-1416Eco-Vector66089210.17816/uroved660892ReviewsНаучные обзорыReviewsReview ArticleMirabegron in the treatment of neurogenic detrusor overactivity: pharmacological and clinical aspectsМирабегрон в лечении нейрогенной детрузорной гиперактивности: фармакологические и клинические аспектыhttps://orcid.org/0000-0002-7724-78322684-4070KuzminIgor V.КузьминИгорь Валентинович
Russian Federation

Dr. Sci. (Medicine), Professor

д-р мед. наук, профессор

kuzminigor@mail.ruAcademician I.P. Pavlov First St. Petersburg State Medical UniversityПервый Санкт-Петербургский государственный медицинский университет им. И.П. Павлова050320250705202515151622402202505032025Copyright ©; 2025, Eco-VectorCopyright ©; 2025, Эко-ВекторCopyright ©; 2025,2025Eco-VectorЭко-Векторhttps://creativecommons.org/licenses/by-nc-nd/4.0/https://journals.eco-vector.com/uroved/article/view/660892

The main cause of the impaired storage function of the bladder in patients with neurogenic dysfunctions of the lower urinary tract is detrusor overactivity, clinically manifested by symptoms of an overactive bladder. The article presents data on the epidemiology, pathogenesis, clinical course and modern approaches to the treatment of detrusor overactivity in neurological patients. It is emphasized that the most important aspect of the clinical course of neurogenic detrusor overactivity is the high risk of upper urinary tract dysfunction, and reducing the threat of kidney damage is the main goal of treating such patients. Pharmacological and clinical aspects of the use of the β3-adrenoreceptor agonist mirabegron in patients with neurogenic bladder dysfunctions are presented. The results of experimental and clinical studies of its use in the treatment of neurogenic detrusor overactivity are presented. A high safety profile of the drug is noted. It is shown that the mechanisms of the therapeutic effect of mirabegron in neurogenic detrusor overactivity include a decrease in detrusor tone, inhibition of spontaneous myocyte contractions, and a decrease in myogenic and urotheliogenic mechanosensory afferent activity. The features of the clinical and urodynamic effects of mirabegron in patients with neurogenic detrusor overactivity in various neurological diseases — multiple sclerosis, Parkinson’s disease, spinal cord injury — are highlighted. The leading role of the results of urodynamic research in choosing the treatment tactics for patients with neurogenic detrusor overactivity is emphasized.

Основной причиной нарушения накопительной функции мочевого пузыря у пациентов с нейрогенными дисфункциями нижних мочевыводящих путей является детрузорная гиперактивность, клинически проявляющаяся симптомами гиперактивного мочевого пузыря. В статье приведены данные относительно эпидемиологии, патогенеза, клинического течения и современных подходов к лечению детрузорной гиперактивности у больных неврологического профиля. Подчеркнуто, что важнейшим аспектом клинического течения нейрогенной детрузорной гиперактивности является высокий риск нарушения функции верхних мочевыводящих путей, а снижение угрозы поражения почек — основная задача лечения таких пациентов. Представлены фармакологические и клинические аспекты применения агониста β3-адренорецепторов мирабегрона у пациентов с нейрогенными дисфункциями мочевого пузыря. Приведены результаты экспериментальных и клинических исследований его использования при лечении нейрогенной детрузорной гиперактивности. Отмечен высокий профиль безопасности препарата. Показано, что механизмы лечебного эффекта мирабегрона при нейрогенной детрузорной гиперактивностью включают снижение тонуса детрузора, торможение спонтанных сокращений миоцитов и уменьшение миогенной и уротелиогенной механосенсорной афферентной активности. Выделены особенности клинического и уродинамического эффектов мирабегрона у пациентов с нейрогенной детрузорной гиперактивностью при разных неврологических заболеваниях — рассеянном склерозе, болезни Паркинсона, травме спинного мозга. Подчеркнута ведущая роль результатов уродинамического исследования при выборе тактики лечения таких пациентов.

overactive bladderneurogenic detrusor overactivityneurogenic bladdermirabegronβ3-adrenoceptor agonistsгиперактивный мочевой пузырьнейрогенная детрузорная гиперактивностьнейрогенный мочевой пузырьмирабегронагонист β3-адренорецепторовAll-Russian public organization “Russian Society of Urologists”. Neurogenic dysfunction of the lower urinary tract. Clinical recommendations of the Ministry of Health of the Russian Federation. 2020. 48 p. (In Russ.)Nikolaev AM, Protoshchak VV, Paronnikov MV, et al. Principles of diagnosis and treatment of post-traumatic neurogenic lower urinary tract dysfunction. Urology reports (St. Petersburg). 2024;14(4): 435–447. doi: 10.17816/uroved630073Kuzmin IV. Dysfunctions of the lower urinary tract in patients with multiple sclerosis. Pathogenesis, symptomatics, diagnosis. Urology reports (St. Petersburg). 2023;13(2):145–156. doi: 10.17816/uroved529654 EDN: GMRFMIMcDonald C, Winge K, Burn DJ. Lower urinary tract symptoms in Parkinson’s disease: Prevalence, aetiology and management. Parkinsonism Relat Disord. 2017;35:8–16. doi: 10.1016/j.parkreldis.2016.10.024Kasyan GR, Dreval RO, Krivoborodov GG, et al. Socio-economic aspects of neurogenic dysfunctions in urology. Urologiia. 2020;(5): 127–132. doi: 10.18565/urology.2020.5.127-132 EDN: LKMZZHBlok B, Castro-Diaz D, Del Popolo G, et al. Guideline of European Urological Association. 2024. Available from: https://uroweb.org/guideline/neuro-urologyGajewski JB, Schurch B, Hamid R, et al. An International Continence Society (ICS) report on the terminology for adult neurogenic lower urinary tract dysfunction (ANLUTD). Neurourol Urodyn. 2018;37(3):1152–1161. doi: 10.1002/nau.23397Ruffion A, Castro-Diaz D, Patel H, et al. Systematic review of the epidemiology of urinary incontinence and detrusor overactivity among patients with neurogenic overactive bladder. Neuroepidemiology. 2013;41(3–4):146–155. doi: 10.1159/000353274Kuzmin IV. Pathogenesis, clinical course and treatment of overactive bladder [dissertation]. Saint Petersburg; 2007. EDN: QECRJB (In Russ.)Quarto G, Autorino R, Gallo A, et al. Quality of life in women with multiple sclerosis and overactive bladder syndrome. Int Urogynecol J Pelvic Floor Dysfunct. 2007;18(2):189–194. doi: 10.1007/s00192-006-0131-9Mehnert U, Chartier-Kastler E, de Wachter S, et al. The management of urine storage dysfunction in the neurological patient. SN Compr Clin Med. 2019;(1):160–182. doi: 10.1007/s42399-018-0005-8Averbeck MA, Madersbacher H. Follow-up of the neuro-urological patient: a systematic review. BJU Int. 2015;115(S6):39–46. doi: 10.1111/bju.13084Kavanagh A, Baverstock R, Campeau L, et al. Canadian Urological Association guideline: Diagnosis, management, and surveillance of neurogenic lower urinary tract dysfunction — Full text. Can Urol Assoc J. 2019;13(6):E157–E176. doi: 10.5489/cuaj.5912Medina-Polo J, Adot JM, Allué M, et al. Consensus document on the multidisciplinary management of neurogenic lower urinary tract dysfunction in patients with multiple sclerosis. Neurourol Urodyn. 2020;39(2):762–770. doi: 10.1002/nau.24276Madersbacher H, Mürtz G, Stöhrer M. Neurogenic detrusor overactivity in adults: a review on efficacy, tolerability and safety of oral antimuscarinics. Spinal Cord. 2013;51(6):432–441. doi: 10.1038/sc.2013.19Kuzmin IV, Kuzmina SV. Anticholinergic therapy of an overactive bladder: clinical practice aspects. Russian Medical Inquiry. 2021;5(5):273–279. doi: 10.32364/2587-6821-2021-5-5-273-279 EDN: WABDWMKulchavenya EV, Kholtobin DP. Overactive bladder in a complicated patient: which drug to choose? Urologiia. 2021;(1):120–125. doi: 10.18565/urology.2021.1.120-12 EDN: XCGKDUKuzmin IV, Kuzmina SV. Treatment of urinary disorders in patients with multiple sclerosis: A review. Consilium Medicum. 2024;26(7):445–451. doi: 10.26442/20751753.2024.7.202887 EDN: AEIISSHegde SS. Muscarinic receptors in the bladder: from basic research to therapeutics. Br J Pharmacol. 2006;147(S2):S80–87. doi: 10.1038/sj.bjp.0706560Pontari MA, Braverman AS, Ruggieri MR Sr. The M2 muscarinic receptor mediates in vitro bladder contractions from patients with neurogenic bladder dysfunction. Am J Physiol Regul Integr Comp Physiol. 2004;286(5):R874–880. doi:10.1152/ajpregu.00391.2003Chancellor M, Boone T. Anticholinergics for overactive bladder therapy: central nervous system effects. CNS Neurosci Ther. 2012;18(2):167–174. doi: 10.1111/j.1755-5949.2011.00248.xKuzmin IV, Slesarevskaya MN. Anticholinergic bladder therapy: geriatric aspects. Clinical Gerontology. 2021;27(11–12):21–34. doi: 10.26347/1607-2499202111-12021-034 EDN: ZHMMTRAndretta E, Finazzi Agrò E, Calabrese M, et al. Antimuscarinics for neurogenic overactive bladder in multiple sclerosis: real-life data. Ther Adv Urol. 2022;14:17562872221122484. doi: 10.1177/17562872221122484Kuzmin IV. Personalized approach to pharmacotherapy of overactive bladder. Urology reports (St. Petersburg). 2023;13(3):267–282. doi: 10.17816/uroved569404 EDN: XJVYUGManack A, Motsko SP, Haag-Molkenteller C, et al. Epidemiology and healthcare utilization of neurogenic bladder patients in a US claims database. Neurourol Urodyn. 2011;30(3):395–401. doi: 10.1002/nau.21003Krivoborodov GG, Kuzmin IV, Romikh VV. Аbobotulinum toxin A (Dysport®) for the treatment of neurogenic detrusor overactivity. Urologiia. 2023;(2):122–129. doi: 10.18565/urology.2023.2.122-129 EDN: CBOGMKChapple CR, Dvorak V, Radziszewski P, Van Kerrebroeck P, et al. A phase II dose-ranging study of mirabegron in patients with overactive bladder. Int Urogynecol J. 2013;24(9):1447–1458. doi: 10.1007/s00192-013-2042-xNitti VW, Chapple CR, Walters C, et al. Safety and tolerability of the β3 -adrenoceptor agonist mirabegron, for the treatment of overactive bladder: results of a prospective pooled analysis of three 12-week randomised Phase III trials and of a 1-year randomised Phase III trial. Int J Clin Pract. 2014;68(8):972–985. doi: 10.1111/ijcp.12433Russian Society of Obstetricians and Gynecologists, All-Russian Public Organization “Russian Society of Urologists”, All-Russian Public Organization “Russian Association of Gerontologists and Geriatricians”. Urinary incontinence. clinical recommendations of the Ministry of Health of the Russian Federation. 2024. (In Russ.)Harding CK, Lapitan MC, Arlandis S, et al. Management of non-neurogenic female lower urinary tract symptoms (LUTS). EAU Guideline. European Association of Urology; 2024. Available from: https://uroweb.org/guidelines/non-neurogenic-female-lutsKrauwinkel W, Dickinson J, Schaddelee M, et al. The effect of mirabegron, a potent and selective β3-adrenoceptor agonist, on the pharmacokinetics of CYP2D6 substrates desipramine and metoprolol. Eur J Drug Metab Pharmacokinet. 2014;39(1):43–52. doi: 10.1007/s13318-013-0133-1Liao C-H, Kuo H-C. High satisfaction with direct switching from antimuscarinics to mirabegron in patients receiving stable antimuscarinic treatment. Medicine (Baltimore). 2016;95(45):e4962. doi: 10.1097/MD.000000000000496238Dyakov IN, Kasyan GR. Pharmacoeconomic feasibility of using Mirabegron in patients with overactive bladder. Good Clinical Practice. 2021;(1):35–45. doi: 10.37489/2588-0519-2021-1-35-45 EDN: EESOPZKolbin AS, Vilyum IA, Proskurin MA, Balykina YuE. Pharmacoeconomic analysis of using Mirabegron to treat overactive bladder in the setting of the Russian Federation health care. Urologiia. 2016;(1:)32–39. EDN: VTRFFHFujimura T, Tamura K, Tsutsumi T, et al. Expression and possible functional role of the beta3-adrenoceptor in human and rat detrusor muscle. J Urol. 1999;161(2):680–685. doi: 10.1016/S0022-5347(01)61994-3Takeda M, Obara K, Mizusawa T, et al. Evidence for beta3-adrenoceptor subtypes in relaxation of the human urinary bladder detrusor: analysis by molecular biological and pharmacological methods. J Pharmacol Exp Ther. 1999;288(3):1367–1373. doi: 10.1016/S0022-3565(24)38094-2Andersson K-E, Arner A. Urinary bladder contraction and relaxation: physiology and pathophysiology. Physiol Rev. 2004;84(3):935–986. doi: 10.1152/physrev.00038.2003Aizawa N, Ichihara K, Fukuhara H, et al. Characteristics of the mechanosensitive bladder afferent activities in relation with microcontractions in male rats with bladder outlet obstruction. Sci Rep. 2017;7(1):7646. doi: 10.1038/s41598-017-07898-yIgawa Y, Aizawa N, Michel MC. β3-Adrenoceptors in the normal and diseased urinary bladder — What are the open questions? Br J Pharmacol. 2019;176(14):2525–2538. doi: 10.1111/bph.14658Michel MC, Korstanje C. β3-Adrenoceptor agonists for overactive bladder syndrome: Role of translational pharmacology in a repositioning clinical drug development project. Pharmacol Ther. 2016;159:66–82. doi: 10.1016/j.pharmthera.2016.01.007Okeke K, Angers S, Bouvier M, Michel MC. Agonist-induced desensitisation of β3-adrenoceptors: Where, when, and how? Br J Pharmacol. 2019;176(14):2539–2558. doi: 10.1111/bph.14633D’ Agostino G, Maria Condino A, Calvi P. Involvement of β3-adrenoceptors in the inhibitory control of cholinergic activity in human bladder: Direct evidence by [(3)H]-acetylcholine release experiments in the isolated detrusor. Eur J Pharmacol. 2015;758:115–122. doi: 10.1016/j.ejphar.2015.03.074Coelho A, Antunes-Lopes T, Gillespie J, Cruz F. Beta-3 adrenergic receptor is expressed in acetylcholine-containing nerve fibers of the human urinary bladder: An immunohistochemical study. Neurourol Urodyn. 2017;36(8):1972–1980. doi: 10.1002/nau.23224Kwon J, Kim DY, Cho KJ, et al. Pathophysiology of overactive bladder and pharmacologic treatments including β3-adrenoceptor agonists — basic research perspectives. Int Neurourol J. 2024;28(S1):S2–33. doi: 10.5213/inj.2448002.001Nitti VW, Rosenberg S, Mitcheson DH, et al. Urodynamics and safety of the β3-adrenoceptor agonist Mirabegron in males with lower urinary tract symptoms and bladder outlet obstruction. J Urol. 2013;190(4):1320–1327. doi: 10.1016/j.juro.2013.05.062Kaidoh K, Igawa Y, Takeda H, et al. Effects of selective beta2 and beta3-adrenoceptor agonists on detrusor hyperreflexia in conscious cerebral infarcted rats. J Urol. 2002;168(3):1247–1252. doi: 10.1016/S0022-5347(05)64634-4Beauval JB, Guilloteau V, Cappellini M, et al. Comparison of tht effects of β3-adrenoceptor agonism on urinary bladder function in conscious, anesthetized, and spinal cord injured rats. Neurourol Urodyn. 2015;34(6):578–585. doi: 10.1002/nau.22629Wada N, Shimizu T, Takai S, et al. Combinational effects of muscarinic receptor inhibition and β3-adrenoceptor stimulation on neurogenic bladder dysfunction in rats with spinal cord injury. Neurourol Urodyn. 2017;36(4):1039–1045. doi: 10.1002/nau.23066El Helou E, Labaki C, Chebel R, et al. The use of mirabegron in neurogenic bladder: a systematic review. World J Urol. 2020;38(10):2435–2442. doi: 10.1007/s00345-019-03040-xElkhashab MM, Alqahtani AM, Kim MH, et al. Safety and efficacy of beta-3 adrenergic agonists in treating neurogenic lower urinary tract dysfunction: A systematic review and meta-analysis. Investig Clin Urol. 2024;65(3):217–229. doi: 10.4111/icu.20230271Zhou Z, Wang X, Li X, Liao L. Detrusor relaxing agents for neurogenic detrusor overactivity: a systematic review, meta-analysis and network meta-analysis. BJU Int. 2024;133(1):25–33. doi: 10.1111/bjuBrucker BM, Jericevic D, Rude T, et al. Mirabegron versus solifenacin in multiple sclerosis patients with overactive bladder symptoms: A prospective comparative nonrandomized study. Urology. 2020;145:94–99. doi: 10.1016/j.urology.2020.08.008Glykas I, Fragkoulis C, Mitsikostas DD, et al. B3 agonists or anticholinergics in the treatment of the lower urinary tract dysfunction in patients with multiple sclerosis? — A randomized study. World J Urol. 2021;39(8):3049–3056. doi: 10.1007/s00345-020-03555-8Mut SE, Selcuk F, İncirli SU, Delibas S. Efficacy and safety of mirabegron add-on therapy after failure with solifenacin in multiple sclerosis patients with overactive bladder: A pilot study. Clin Neuropharmacol. 2024;47(4):109–112. doi: 10.1097/WNF.0000000000000596Zachariou A, Filiponi M, Baltogiannis D, et al. Effective treatment of neurogenic detrusor overactivity in multiple sclerosis patients using desmopressin and mirabegron. Can J Urol. 2017;24(6): 9107–9113.Akkoc Y. Efficacy and safety of mirabegron for treatment of neurogenic detrusor overactivity in adults with spinal cord injury or multiple sclerosis: a systematic review. Spinal Cord. 2022;60(10):854–861. doi: 10.1038/s41393-022-00853-3Peyronnet B, Vurture G, Palma J-A, et al. Mirabegron in patients with Parkinson disease and overactive bladder symptoms: A retrospective cohort. Parkinsonism Relat Disord. 2018;57:22–26. doi: 10.1016/j.parkreldis.2018.07.005Gubbiotti M, Conte A, Di Stasi SM, et al. Feasibility of mirabegron in the treatment of overactive bladder in patients affected by Parkinson’s disease: A pilot study. Ther Adv Neurol Disord. 2019;12:1756286419843458. doi: 10.1177/1756286419843458Cho SY, Jeong SJ, Lee S, et al. Mirabegron for treatment of overactive bladder symptoms in patients with Parkinson’s disease: A double-blind, randomized placebo-controlled trial (Parkinson’s Disease Overactive bladder Mirabegron, PaDoMi study). Neurourol Urodyn. 2021;40(1):286–294. doi: 10.1002/nau.24552Moussa M, Chakra MA, Dabboucy B, et al. The safety and effectiveness of Mirabegron in Parkinson’s disease patients with overactive bladder: a randomized controlled trial. Scand J Urol. 2022;56(1):66–72. doi: 10.1080/21681805.2021.1990994Madan A, Brown T, Ray S, et al. A novel trial of Mirabegron and behavioral modification including pelvic floor exercise for overactive bladder in Parkinson’s disease (MAESTRO). Cureus. 2022;14(11): e31818. doi: 10.7759/cureus.31818Cheng B, Huang S, Huang Q, et al. The efficacy and safety of medication for treating overactive bladder in patients with Parkinson’s disease: a meta-analysis and systematic review of randomized double-blind placebo-controlled trials. Int Urogynecol J. 2023;34(9):2207–2216. doi: 10.1007/s00192-023-05528-yWöllner J, Pannek J. Initial experience with the treatment of neurogenic detrusor overactivity with a new β-3 agonist (Mirabegron) in patients with spinal cord injury. Spinal Cord. 2016;54(1):78–82. doi: 10.1038/sc.2015.195Welk B, Hickling D, McKibbon M, et al. A pilot randomized-controlled trial of the urodynamic efficacy of Mirabegron for patients with neurogenic lower urinary tract dysfunction. Neurourol Urodyn. 2018;37(8):2810–2817. doi: 10.1002/nau.23774Krhut J, Borovička V, Bílková K, et al. Efficacy and safety of Mirabegron for the treatment of neurogenic detrusor overactivity — Prospective, randomized, double-blind, placebo-controlled study. Neurourol Urodyn. 2018;37(7):2226–2233. doi: 10.1002/nau.23566Trbovich M, Romo T, Polk M, et al. The treatment of neurogenic lower urinary tract dysfunction in persons with spinal cord injury: An open label, pilot study of anticholinergic agent vs. Mirabegron to evaluate cognitive impact and efficacy. Spinal Cord Ser Cases. 2021;7(1):50. doi: 10.1038/s41394-021-00413-6Vasudeva P, Prasad V, Yadav S, et al. Efficacy and safety of Mirabegron for the treatment of neurogenic detrusor overactivity resulting from traumatic spinal cord injury: A prospective study. Neurourol Urodyn. 2021;40(2):666–671. doi: 10.1002/nau.24604Han S-H, Cho IK, Jung JH, et al. Long-term efficacy of Mirabegron add-on therapy to antimuscarinic agents in patients with spinal cord injury. Ann Rehabil Med. 2019;43(1):54–61. doi: 10.5535/arm.2019.43.1.54Krebs J, Pannek J, Rademacher F, Wöllner J. Real-world effects of Mirabegron in patients with chronic neurogenic detrusor overactivity — A retrospective cohort study. Res Rep Urol. 2020;12:187–192. doi: 10.2147/RRU.S253713Park JS, Lee YS, Lee CN, et al. Efficacy and safety of Mirabegron, a β3-adrenoceptor agonist, for treating neurogenic bladder in pediatric patients with spina bifida: a retrospective pilot study. World J Urol. 2019;37(8):1665–1670. doi: 10.1007/s00345-018-2576-0Sager C, Sanmartino M, Burek C, et al. Efficacy and safety of Mirabegron as adjuvant treatment in children with refractory neurogenic bladder dysfunction. J Pediatr Urol. 2020;16(5):655.e1–655.e6. doi: 10.1016/j.jpurol.2020.07.020Baka-Ostrowska M, Bolong DT, Persu C, et al. Efficacy and safety of Mirabegron in children and adolescents with neurogenic detrusor overactivity: An open-label, phase 3, dose-titration study. Neurourol Urodyn. 2021;40(6):1490–1499. doi: 10.1002/nau.24657van Veen FEE, Schotman M, ‘t Hoen LA, et al. Long-term beneficial effects of Mirabegron in pediatric patients with therapy-refractory neurogenic lower urinary tract dysfunction. J Pediatr Urol. 2023;19(6):753.e1–753.e8. doi: 10.1016/j.jpurol.2023.08.015Przydacz M, Chlosta P, Corcos J. Recommendations for urological follow-up of patients with neurogenic bladder secondary to spinal cord injury. Int Urol Nephrol. 2018;50(6):1005–1016. doi: 10.1007/s11255-018-1852-7de Groat WC. A neurologic basis for the overactive bladder. Urology. 1997;50(6S1):36–52. doi: 10.1016/s0090-4295(97)00587-6Andersson K-E. Antimuscarinic mechanisms and the overactive detrusor: an update. Eur Urol. 2011;59(3):377–386. doi: 10.1016/j.eururo.2010.11.040