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Drug Treatment

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Handbook of Neurourology

Abstract

A short review is given of current literature on medical alternatives for managing neurogenic bladder (NGB) by treating detrusor overactivity (NDO) and improving bladder compliance and urinary incontinence. The first goal of treatment of NGB is to protect the upper tract from damage, and the second is to maintain urinary continence, but all the while maintaining the patient’s quality of life. The use of antimuscarinics, α-adrenoceptor antagonists, β-adrenoceptor agonists, baclofen, and cannabinoids will be discussed.

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References

  1. M.J. Drake, A. Apostolidis, A. Cocci, et al., Neurogenic lower urinary tract dysfunction: Clinical management recommendations of the neurologic incontinence committee of the fifth international consultation on incontinence 2013. Neurourol. Urodyn. 35, 657–665 (2016)

    Article  PubMed  Google Scholar 

  2. R.M. Sturm, E.Y. Cheng, The management of the pediatric neurogenic bladder. Curr Bladder Dysfunct Rep. 11, 225–233 (2016)

    Article  PubMed  PubMed Central  Google Scholar 

  3. K.I. Tudor, R. Sakakibara, J.N. Panicker, Neurogenic lower urinary tract dysfunction: Evaluation and management. J. Neurol. 263, 2555–2564 (2016)

    Article  PubMed  Google Scholar 

  4. J.J. Wyndaele, The management of neurogenic lower urinary tract dysfunction after spinal cord injury. Nat. Rev. Urol. 13, 705–714 (2016)

    Article  PubMed  Google Scholar 

  5. P. Abrams, L. Cardozo, M. Fall, et al., Standardisation sub-committee of the international continence society. The standardisation of terminology of lower urinary tract function: Report from the standardisation sub-committee of the international continence society. Neurourol. Urodyn. 21, 167–178 (2002)

    Article  PubMed  Google Scholar 

  6. M. Stöhrer, B. Blok, D. Castro-Diaz, et al., EAU guidelines on neurogenic lower urinary tract dysfunction. Eur. Urol. 56, 81–88 (2009)

    Article  PubMed  Google Scholar 

  7. A.P. Cameron, L.P. Wallner, D.G. Tate, et al., Bladder management after spinal cord injury in the United States 1972 to 2005. J. Urol. 184, 213–217 (2010)

    Article  PubMed  Google Scholar 

  8. A. Borau, J.M. Adot, M. Allué, et al., A systematic review of the diagnosis and treatment of patients with neurogenic hyperactivity of the detrusor muscle. Actas Urol. Esp. 42, 5–16 (2017)

    Article  PubMed  Google Scholar 

  9. P. Abrams, K.E. Andersson, J.J. Buccafusco, et al., Muscarinic receptors: Their distribution and function in body systems, and the implications for treating overactive bladder. Br. J. Pharmacol. 148, 565–578 (2006)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. K.E. Andersson, Muscarinic acetylcholine receptors in the urinary tract. Handb. Exp. Pharmacol. 202, 319–344 (2011)

    Article  CAS  Google Scholar 

  11. A.S. Braverman, G.R. Luthin, M.R. Ruggieri, M2 muscarinic receptor contributes to contraction of the denervated rat urinary bladder. Am. J. Phys. 275, 1654–1660 (1998)

    Google Scholar 

  12. M.A. Pontari, A.S. Braverman, M.R. Ruggieri Sr., The M2 muscarinic receptor mediates in vitro bladder contractions from patients with neurogenic bladder dysfunction. Am. J. Phys. 286, 874–880 (2004)

    Google Scholar 

  13. T. Schneider, P. Hein, M. Michel-Reher, et al., Effects of ageing on muscarinic receptor subtypes and function in rat urinary bladder. Naunyn Schmiedeberg's Arch. Pharmacol. 372, 71–78 (2005a)

    Article  CAS  Google Scholar 

  14. T. Schneider, P. Hein, J. Bai, et al., A role for muscarinic receptors or rho-kinase in hypertension associated rat bladder dysfunction? J. Urol. 173, 2178–2181 (2005b)

    Article  CAS  PubMed  Google Scholar 

  15. M. Yoshida, Y. Homma, A. Inadome, et al., Age-related changes in cholinergic and purinergic neurotransmission in human isolated bladder smooth muscles. Exp. Gerontol. 3, 99–109 (2001)

    Article  Google Scholar 

  16. M. Yoshida, K. Masunaga, Y. Satoji, et al., Basic and clinical aspects of non-neuronal acetylcholine: Expression of non-neuronal acetylcholine in urothelium and its clinical significance. J. Pharmacol. Sci. 106, 193–198 (2008)

    Article  CAS  PubMed  Google Scholar 

  17. D.E. Rapp, M.B. Lyon, G.T. Bales, et al., A role for the P2X receptor in urinary tract physiology and in the pathophysiology of urinary dysfunction. Eur. Urol. 48, 303–308 (2005)

    Article  CAS  PubMed  Google Scholar 

  18. S.N. Datta, A. Roosen, A. Pullen, et al., Immunohistochemical expression of muscarinic receptors in the urothelium and suburothelium of neurogenic and idiopathic overactive human bladders, and changes with botulinum neurotoxin administration. J. Urol. 184, 2578–2585 (2010)

    Article  CAS  PubMed  Google Scholar 

  19. K.E. Andersson, L. Cardozo, F. Cruz, et al. Pharmacological treatment of urinary incontinence. In: Abrams P, Cardozo L, Wagg A, et al, editors. 6th International Consultation on Incontinence, Tokyo, September 2016, The International Continence Society (ICS) and the International Consultation on Urological Diseases (ICUD) (2017)

    Google Scholar 

  20. P. Madhuvrata, M. Singh, Z. Hasafa, et al., Anticholinergic drugs for adult neurogenic detrusor overactivity: A systematic review and meta-analysis. Eur. Urol. 62, 816–830 (2012)

    Article  CAS  PubMed  Google Scholar 

  21. S.L. Gray, M.L. Anderson, S. Dublin, et al., Cumulative use of strong anticholinergics and incident dementia: A prospective cohort study. JAMA Intern. Med. 175, 401–407 (2015)

    Article  PubMed  PubMed Central  Google Scholar 

  22. M. Naja, J. Zmudka, S. Hannat, et al., In geriatric patients, delirium symptoms are related to the anticholinergic burden. Geriatr. Gerontol. Int. 16, 424–431 (2016)

    Article  PubMed  Google Scholar 

  23. D.C. Moga, E.L. Abner, Q. Wu, et al., Bladder antimuscarinics and cognitive decline in elderly patients. Alzheimers Dement (NY) 3, 139–148 (2017)

    Article  Google Scholar 

  24. E. Esin, A. Ergen, M. Cankurtaran, et al., Influence of antimuscarinic therapy on cognitive functions and quality of life in geriatric patients treated for overactive bladder. Aging Ment. Health 19, 217–223 (2015)

    Article  PubMed  Google Scholar 

  25. S. Swami, R.A. Cohen, J.A. Kairalla, et al., Anticholinergic drug use and risk to cognitive performance in older adults with questionable cognitive impairment: A cross-sectional analysis. Drugs Aging 33, 809–818 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. H. Madersbacher, G. Mürtz, M. Stöhrer, Neurogenic detrusor overactivity in adults: A review on efficacy, tolerability and safety of oral antimuscarinics. Spinal Cord 51, 432–441 (2013)

    Article  CAS  PubMed  Google Scholar 

  27. M. Horstmann, T. Schaefer, Y. Aguilar, et al., Neurogenic bladder treatment by doubling the recommended antimuscarinic dosage. Neurourol. Urodyn. 25, 441–445 (2006)

    Article  CAS  PubMed  Google Scholar 

  28. B. Amend, J. Hennenlotter, T. Schäfer, et al., Effective treatment of neurogenic detrusor dysfunction by combined high-dosed antimuscarinics without increased side-effects. Eur. Urol. 53, 1021–1028 (2008)

    Article  CAS  PubMed  Google Scholar 

  29. K. Waldeck, B. Larsson, K.E. Andersson, Comparison of oxybutynin and its active metabolite, N-desethyl-oxybutynin, in the human detrusor and parotid gland. J. Urol. 157, 1093–1097 (1997)

    Article  CAS  PubMed  Google Scholar 

  30. J.G. Ouslander, J. Blaustein, A. Connor, et al., Pharmacokinetics and clinical effects of oxybutynin in geriatric patients. J. Urol. 140, 47–50 (1988)

    Article  CAS  PubMed  Google Scholar 

  31. M.J. Kennelly, A comparative review of oxybutynin chloride formulations: Pharmacokinetics and therapeutic efficacy in overactive bladder. Rev. Urol. 12, 12–19 (2010)

    PubMed  PubMed Central  Google Scholar 

  32. K. Jirschele, P.K. Sand, Oxybutynin: Past, present, and future. Int. Urogynecol. J. 24, 595–604 (2013)

    Article  PubMed  Google Scholar 

  33. Y.E. Yarker, K.L. Goa, A. Fitton, Oxybutynin. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic use in detrusor instability. Drugs Aging 6, 243–262 (1995)

    Article  CAS  PubMed  Google Scholar 

  34. J.W. Thüroff, E. Chartier-Kastler, J. Corcus, et al., Medical treatment and medical side effects in urinary incontinence in the elderly. World J. Urol. 16, S48–S61 (1998)

    Article  PubMed  Google Scholar 

  35. R.M. Hussain, K. Hartigan-Go, S.H.L. Thomas, et al., Effect of oxybutynin on the QTc interval in elderly patients with urinary incontinence. Br. J. Clin. Pharmacol. 37, 485 (1994)

    Google Scholar 

  36. A.M. Arisco, E.K. Brantly, S.R. Kraus, Oxybutynin extended release for the management of overactive bladder: A clinical review. Drug Des. Devel. Ther. 3, 151–161 (2009)

    CAS  PubMed  PubMed Central  Google Scholar 

  37. R.A. Appell, M.B. Chancellor, R.H. Zobrist, et al., Pharmacokinetics, metabolism, and saliva output during transdermal and extended-release oral oxybutynin administration in healthy subjects. Mayo Clin. Proc. 78, 696 (2003)

    Article  CAS  PubMed  Google Scholar 

  38. M.A. Siddiqui, C.M. Perry, L.J. Scott, Oxybutynin extended- release: A review of its use in the management of overactive bladder. Drugs 64, 885 (2004)

    Article  CAS  PubMed  Google Scholar 

  39. G.G. Kay, U. Ebinger, Preserving cognitive function for patients with overactive bladder: Evidence for a differential effect with darifenacin. Int. J. Clin. Pract. 62, 1792–1800 (2008)

    Article  CAS  PubMed  Google Scholar 

  40. D. Pagoria, R.C. O’Connor, M.L. Guralnick, Antimuscarinic drugs: Review of the cognitive impact when used to treat overactive bladder in elderly patients. Curr. Urol. Rep. 12, 351–357 (2011)

    Article  PubMed  Google Scholar 

  41. C.J. Hills, S.A. Winter, J.A. Balfour, Tolterodine. Drugs 55, 813–820 (1998)

    Article  CAS  PubMed  Google Scholar 

  42. D. Clemett, B. Jarvis, Tolterodine: A review of its use in the treatment of overactive bladder. Drugs Aging 18, 277–304 (2001)

    Article  CAS  PubMed  Google Scholar 

  43. S. Salvatore, M. Serati, P. Bolis, Tolterodine for the treatment of overactive bladder. Expert. Opin. Pharmacother. 9, 1249–1255 (2008)

    Article  CAS  PubMed  Google Scholar 

  44. P. Van Kerrebroeck, K. Kreder, U. Jonas, et al., Tolterodine study group. Tolterodine once-daily: Superior efficacy and tolerability in the treatment of the overactive bladder. Urology 57, 414–421 (2001)

    Article  PubMed  Google Scholar 

  45. M. Watanabe, T. Yamanishi, M. Honda, et al., Efficacy of extended-release tolterodine for the treatment of neurogenic detrusor overactivity and/or low-compliance bladder. Int. J. Urol. 17, 931–936 (2010)

    Article  CAS  PubMed  Google Scholar 

  46. B.K. Malhotra, P. Glue, K. Sweeney, et al., Thorough QT study with recommended and supratherapeutic doses of tolterodine. Clin. Pharmacol. Ther. 81, 377–385 (2007)

    Article  CAS  PubMed  Google Scholar 

  47. I. Fusgen, D. Hauri, Trospium chloride: An effective option for medical treatment of bladder overactivity. Int. J. Clin. Pharmacol. Ther. 38, 223 (2000)

    Article  CAS  PubMed  Google Scholar 

  48. O. Doroshyenko, A. Jetter, K.P. Odenthal, et al., Clinical pharmacokinetics of trospium chloride. Clin. Pharmacokinet. 44, 701 (2005)

    Article  CAS  PubMed  Google Scholar 

  49. Y. Kim, N. Yoshimura, H. Masuda, et al., Antimuscarinic agents exhibit local inhibitory effects on muscarinic receptors in bladder-afferent pathways. Urology 65, 238–242 (2005)

    Article  PubMed  Google Scholar 

  50. D. Staskin, G. Kay, C. Tannenbaum, et al., Trospium chloride has no effect on memory testing and is assay undetectable in the central nervous system of older patients with overactive bladder. Int. J. Clin. Pract. 64, 1294–1300 (2010)

    Article  CAS  PubMed  Google Scholar 

  51. M.B. Chancellor, D.R. Staskin, G.G. Kay, et al., Blood-brain barrier permeation and efflux exclusion of anticholinergics used in the treatment of overactive bladder. Drugs Aging 29, 259–273 (2012)

    Article  CAS  PubMed  Google Scholar 

  52. M. Stöhrer, P. Bauer, B.M. Giannetti, et al., Effect of trospium chloride on urodynamic parameters in patients with detrusor hyperreflexia due to spinal cord injuries: A multicentre placebo controlled double-blind trial. Urol. Int. 47, 138 (1991)

    Article  PubMed  Google Scholar 

  53. H. Madersbacher, M. Stohrer, R. Richter, et al., Trospium chloride versus oxybutynin: A randomized, double-blind, multicentre trial in the treatment of detrusor hyper-reflexia. Br. J. Urol. 75, 452 (1995)

    Article  CAS  PubMed  Google Scholar 

  54. S. Allousi, K.-U. Laval, R. Eckert, Trospium chloride (Spasmolyt) in patients with motor urge syndrome (detrusor instability): A double-blind, randomised, multicentre, placebo-controlled study. J Clin Res. 1, 439 (1998)

    Google Scholar 

  55. M. Halaska, G. Ralph, A. Wiedemann, et al., Controlled, double-blind, multicentre clinical trial to investigate long-term tolerability and efficacy of trospium chloride in patients with detrusor instability. World J. Urol. 20, 392 (2003)

    Article  CAS  PubMed  Google Scholar 

  56. N. Zinner, M. Gittelman, R. Harris, et al., Trospium study group. Trospium chloride improves overactive bladder symptoms: A multicenter phase III trial. J. Urol. 171, 2311 (2004a)

    Article  CAS  PubMed  Google Scholar 

  57. R.H. Bödeker, H. Madersbacher, C. Neumeister, et al., Dose escalation improves therapeutic outcome: Post hoc analysis of data from a 12-week, multicentre, double-blind, parallel-group trial of trospium chloride in patients with urinary urge incontinence. BMC Urol. 10, 15 (2010)

    Article  PubMed  PubMed Central  Google Scholar 

  58. N. Silver, B. Sandage, L. Sabounjian, et al., Pharmacokinetics of once-daily trospium chloride 60 mg extended release and twice-daily trospium chloride20 mg in healthy adults. J. Clin. Pharmacol. 50, 143–150 (2010)

    Article  CAS  PubMed  Google Scholar 

  59. D.R. Staskin, M.T. Rosenberg, P.K. Sand, et al., Trospium chloride once-daily extended release is effective and well tolerated for the treatment of overactive bladder syndrome: An integrated analysis of two randomised, phase III trials. Int. J. Clin. Pract. 63, 1715–1723 (2009)

    Article  CAS  PubMed  Google Scholar 

  60. A. Haruno, Inhibitory effects of propiverine hydrochloride on the agonist-induced or spontaneous contractions of various isolated muscle preparations. Arzneimittelforschung 42(6), 815–817 (1992, June)

    CAS  PubMed  Google Scholar 

  61. K. Andersson, Pharmacologic treatment of urinary incontinence, in Incontinence, 6th ed., P. Abrams, L. Cardozo, A. Wagg and A. Wein, Eds., 2017, pp. 805–957

    Google Scholar 

  62. M. Wuest, A. Weiss, M. Waelbroeck, M. Braeter, L. Kelly, O. Hakenberg, U. Ravens, Propiverine and metabolites: Differences in binding to muscarinic receptors and in functional models of detrusor contraction. Naunyn Schmiedeberg's Arch. Pharmacol. 374(2), 87–97 (2006, November)

    Article  CAS  Google Scholar 

  63. H. Madersbacher, G. Mürtz, Efficacy, tolerability and safety profile of propiverine in the treatment of the overactive bladder (non-neurogenic and neurogenic). World J. Urol. 19(5), 324–335 (2001, November)

    Article  CAS  PubMed  Google Scholar 

  64. M. Stöhrer, G. Mürtz, H. Madersbacher, Neurogenic detrusor overactivity in adults: A review on efficacy, tolerability and safety of oral antimuscarinics. Spinal Cord 51(6), 432–441 (2013, May)

    Article  PubMed  Google Scholar 

  65. K. McKeage, Propiverine: A review of its use in the treatment of adults and children with overactive bladder associated with idiopathic or neurogenic detrusor overactivity, and in men with lower urinary tract symptoms. Clin. Drug Investig. 33(1), 71–91 (2013, January)

    Article  CAS  PubMed  Google Scholar 

  66. M. Stöhrer, G. Mürtz, G. Kramer, W. Warnack, G. Primus, V. Jinga, A. Manu-Marin, N. Calomfirescu, G. Strugala, Efficacy and tolerability of propiverine hydrochloride extended-release compared with immediate-release in patients with neurogenic detrusor overactivity. Spinal Cord 51(5), 419–423 (2013, May)

    Article  PubMed  Google Scholar 

  67. R. Sakakibara, T. Ogata, T. Uchiyama, M. Kishi, E. Ogawa, S. Isaka, J. Yuasa, T. Yamamoto, T. Ito, T. Yamanishi, Y. Awa, C. Yamaguchi, O. Takahashi, How to manage overactive bladder in elderly individuals with dementia? A combined use of donepezil, a central acetylcholinesterase inhibitor, and propiverine, a peripheral muscarine receptor antagonist. J. Am. Geriatr. Soc. 57(8), 1515–1517 (2009, August)

    Article  PubMed  Google Scholar 

  68. M. Oelke, S. Murgas, T. Schneider, E. Heßdörfer, Influence of propiverine er 30 mg once daily on cognitive function in elderly female and male patients with overactive bladder: a non-interventional study to assess real life data, in 43rd Annual Meeting of the ICS, Barcelona (2013)

    Google Scholar 

  69. H. Schulte-Baukloh, G. Mürtz, T. Henne, T. Michael, K. Miller, H. Knispel, Urodynamic effects of propiverine hydrochloride in children with neurogenic detrusor overactivity: A prospective analysis. BJU Int. 97(2), 355–358 (2006, February)

    Article  PubMed  Google Scholar 

  70. U. Grigoleit, G. Mürtz, S. Laschke, M. Schuldt, M. Goepel, G. Kramer, M. Stöhrer, Efficacy, tolerability and safety of propiverine hydrochloride in children and adolescents with congenital or traumatic neurogenic detrusor overactivity–a retrospective study. Eur. Urol. 49(6), 1114–1120 (2006, June)

    Article  CAS  PubMed  Google Scholar 

  71. H. Schulte-Baukloh, G. Mürtz, G. Heine, P. Austin, K. Miler, T. Michael, G. Strugala, H. Knispel, Urodynamic effects of propiverine in children and adolescents with neurogenic bladder: Results of a prospective long-term study. J. Pediatr. Urol. 8, 386–392 (2012)

    Article  PubMed  Google Scholar 

  72. P. Abrams, L. Cardozo, M. Fall, et al., The standardization of terminology in lower urinary tract function: Report from the standardization sub-committee of the international continence society. Urology 61, 37–49 (2003)

    Article  PubMed  Google Scholar 

  73. W. Stewart, R. Herzog, A. Wein, et al., The prevalence and impact of overactive bladder in the US: Results from NOBLE program. Neurourol. Urodyn. 20, 406–408 (2001)

    Google Scholar 

  74. I. Milsom, P. Abrams, L. Cardozo, R.G. Robert, J. Thuroff, A.J. Wein, How widespread are the symptoms of an overactive bladder and how are they managed? A population based prevalence study. BJU Int. 87, 760–766 (2001)

    Article  CAS  PubMed  Google Scholar 

  75. VESIcare [package insert]. Deerfield, II1: Astellas Pharma US, Inc (2004)

    Google Scholar 

  76. O. Doroshyenko, U. Fuhr, Clinical pharmacokinetics and pharmacodynamics of solifenacin. Clin. Pharmacokinet. 48, 281–302 (2009)

    Article  CAS  PubMed  Google Scholar 

  77. R.A. Smulders, W.J. Krauwinkel, P.J. Swart, et al., Pharmacokinetics and safety of solifenacin succinate in healthy young men. J. Clin. Pharmacol. 44, 1023–1033 (2004)

    Article  CAS  PubMed  Google Scholar 

  78. R.A. Smulders, N.N. Smith, W.J. Krauwinkel, et al., Pharmacokinetics, safety, and tolerability of Solifenacin in patients with renal insufficiency. J. Pharmacol. Sci. 103, 67–74 (2007)

    Article  CAS  PubMed  Google Scholar 

  79. M. Kuipers, R. Smulders, W. Krauwinkel, et al., Open-label study of the safety and pharmacokinetics of Solifenacin in subjects with hepatic impairment. J. Pharmacol. Sci. 102, 405–412 (2006)

    Article  CAS  PubMed  Google Scholar 

  80. K.E. Andersson, A.J. Wein, Pharmacology of the lower urinary tract: Basis for current and future treatments of urinary incontinence. Pharmacol. Rev. 56, 581–631 (2004)

    Article  CAS  PubMed  Google Scholar 

  81. S. Sigala, G. Mirabella, A. Peroni, et al., Differential gene expression of cholinergic muscarinic receptor subtypes in male and female normal human urinary bladder. Urology 60, 719–725 (2002)

    Article  PubMed  Google Scholar 

  82. R. Chess-Williams, C.R. Chapple, T. Yamanishi, et al., The minor population of M3-receptors mediates contraction of human detrusor muscle in vitro. J. Auton. Pharmacol. 21, 1–6 (2002)

    Google Scholar 

  83. D.E. Golan, A.H. Tashjian, E.J. Armstrong, et al., Principles of Pharmacology. The Pathophysiologic Basis of Drug Therapy (Lippincott Williams & Wilkins, Baltimore, 2005)

    Google Scholar 

  84. M.P. Caulfield, N.J.M. Birdsall, International Union of Pharmacology XVII. Classification of muscarinic acetylcholine receptors. Pharmacol. Rev. 50, 279–290 (1998)

    CAS  PubMed  Google Scholar 

  85. P. Wang, G.R. Luthin, M.R. Ruggieri, Muscarinic acetylcholine receptor subtypes mediating urinary bladder contractility and coupling to GTP binding proteins. J. Pharmacol. Exp. Ther. 273, 959–966 (1995)

    CAS  PubMed  Google Scholar 

  86. T. Nakamura, J. Kimura, O. Yamaguchi, Muscarinic M2 receptors inhibit Ca2+−activated K+ channels in rat bladder smooth muscle. Int. J. Urol. 9, 689–696 (2002)

    Article  CAS  PubMed  Google Scholar 

  87. M.A. Pontari, A.S. Braverman, S.R. Michael R Ruggieri, et al., The M2 muscarinic receptor mediates in vitro bladder contractions from patients with neurogenic bladder dysfunction. Am. J. Physiol. Regul. Integr. Comp. Physiol. 286, 874–880 (2004)

    Article  Google Scholar 

  88. P.J. Swart, W.J. Krauwinkel, R.A. Smulders, et al., Pharmacokinetic effect of ketoconazole on solifenacin in healthy volunteers. Basic Clin. Pharmacol. Toxicol. 99, 33–36 (2006)

    Article  CAS  PubMed  Google Scholar 

  89. M.E. Taekema-Roelvink, P.J. Swart, M.E. Kuipers, et al., Pharmacokinetic interaction of solifenacin with an oral contraceptive containing ethinyl estradiol and levonorgestrel in healthy women: A double-blind, placebo-controlled study. Clin. Ther. 27, 1403–1410 (2005)

    Article  CAS  PubMed  Google Scholar 

  90. M.C. Michel, T. Minematsu, T. Hashimoto, et al., In vitro studies on the potential of solifenacin for drug-drug interaction: Plasma protein and MDR 1 transport. Br. J. Clin. Pharmacol. 59, 647 (2015)

    Google Scholar 

  91. F.E. Govier, N. Smith, T. Uchida, Efficacy and safety of 10 mg solifenacin succinate in patients with overactive bladder syndrome: Results from a randomized, double-blind, placebo-controlled phase III pivotal trial. Clin Med Insights Urol. 4, 11–20 (2010)

    CAS  Google Scholar 

  92. O. Yamaguchi, E. Marui, H. Kakizaki, et al., Randomized, doubleblind, placebo- and propiverine controlled trial of the once-daily antimuscarinic agent solifenacin in Japanese patients with overactive bladder. BJU Int. 100, 579–587 (2007)

    Article  CAS  PubMed  Google Scholar 

  93. C. Chapple, T. Rechberger, S. Al-Shukri, et al., Randomized, doubleblind placebo-and tolterodine-controlled trial of the once-daily antimuscarinic agent solifenacin in patients with symptomatic overactive bladder. BJU Int. 93, 303–310 (2004)

    Article  CAS  PubMed  Google Scholar 

  94. C.R. Chapple, R. Martinez-Garcia, L. Selvaggi, et al., A comparison of the efficacy and tolerability of solifenacin succinate and extended release tolterodine at treating overactive bladder syndrome: Results of the STAR trial. Eur. Urol. 48, 464–470 (2005)

    Article  CAS  PubMed  Google Scholar 

  95. L. Cardozo, M. Lisec, R. Millard, Randomized, double-blind placebo controlled trial of the once daily antimuscarinic agent solifenacin succinate in patients with overactive bladder. J. Urol. 172, 1919–1924 (2004)

    Article  CAS  PubMed  Google Scholar 

  96. C. Kelleher, L. Cardozo, C. Chapple, Improved quality of life in patients with overactive bladder symptoms treated with solifenacin. BJU Int. 95, 81–85 (2005)

    Article  PubMed  Google Scholar 

  97. L. Cardozo, G. Amarenco, G. Pushkar, et al., Severity of overactive bladder symptoms and response to dose escalation in a randomized, double-blind trial of solifenacin (SUNRISE). BJU Int. 111, 804–810 (2013)

    Article  CAS  PubMed  Google Scholar 

  98. Amarenco G, Sutory M, Zachoval R, Agarwal M, Del Popolo G, Tretter R, Compion G, De Ridder D. Solifenacin is effective and well tolerated in patients with neurogenic detrusor overactivity: Results from the double-blind, randomized, active- and placebo-controlled SONIC urodynamic study. Neurourol. Urodyn. 2017, February;36(2):414–421. https://doi.org/10.1002/nau.22945. Epub 2015 Dec 29

  99. Franco I, Hoebeke P, Baka-Ostrowska M, Bolong D, Davies LN, Dahler E, Snijder R, Stroosma O, Verheggen F, Newgreen D, Bosman B, Vande Walle J. Long-term efficacy and safety of solifenacin in pediatric patients aged 6 months to 18 years with neurogenic detrusor overactivity: Results from two phase 3 prospective open-label studies. J. Pediatr. Urol. 2020, April;16(2):180.e1–180.e8. https://doi.org/10.1016/j.jpurol.2019.12.012. Epub 2019 Dec 27

  100. Brucker BM, Jericevic D, Rude T, Enemchukwu E, Pape D, Rosenblum N, Charlson ER, Zhovtis-Ryerson L, Howard J, Krupp L, Peyronnet B. Mirabegron versus Solifenacin in multiple sclerosis patients with overactive bladder symptoms: A prospective comparative nonrandomized study. Urology 2020, November 145:94–99. https://doi.org/10.1016/j.urology.2020.08.008. Epub 2020 Aug 19

  101. W.D. Steers, Darifenacin: Pharmacology and clinical usage. Urol. Clin. North Am. 33(4), 475–482 (2006, November)

    Article  PubMed  Google Scholar 

  102. P.P. Smith, H.H. Lai, R.A. Appell, Darifenacin: A selective M3 muscarinic receptor antagonist for the treatment of overactive bladder. Therapy 3(6), 723–732 (2006)

    Article  CAS  Google Scholar 

  103. A. Skerjanec, The clinical pharmacokinetics of darifenacin. Clin. Pharmacokinet. 45(4), 325–350 (2006)

    Article  CAS  PubMed  Google Scholar 

  104. S. Carl, S. Laschke, Darifenacin is also effective in neurogenic bladder dysfunction (multiple sclerosis). Urology 68(Suppl), 250 (2006)

    Article  Google Scholar 

  105. P. Vasudeva, A. Kumar, S. Yadav, et al., Neurological safety and efficacy of darifenacin and mirabegron for the treatment of overactive bladder in patients with history of cerebrovascular accident: A prospective study. Neurourol. Urodyn. (2021, September 13). https://doi.org/10.1002/nau.24793. Epub ahead of print

  106. J. Bycroft, B. Leaker, S. Wood, et al., The effect of darifenacin on neurogenic detrusor overactivity in patients with spinal cord injury. Neurourol. Urodyn. 22, A190 (2003)

    Google Scholar 

  107. F. Haab, J. Corcos, P. Siami, et al., Long-term treatment with darifenacin for overactive bladder: Results of a 2-year, open-label extension study. BJU Int. 98(5), 1025–1032 (2006, November)

    Article  CAS  PubMed  Google Scholar 

  108. E. Callegari, B. Malhotra, P.J. Bungay, et al., A comprehensive non-clinical evaluation of the CNS penetration potential of antimuscarinic agents for the treatment of overactive bladder. Br. J. Clin. Pharmacol. 72(2), 235–246 (2011, August)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. G.G. Kay, K.A. Wesnes, Pharmacodynamic effects of darifenacin, a muscarinic M3 selective receptor antagonist for the treatment of overactive bladder, in healthy volunteers. BJU Int. 96, 1055–1062 (2005)

    Article  CAS  PubMed  Google Scholar 

  110. G. Kay, T. Crook, L. Rekeda, et al., Differential effects of the antimuscarinic agent’s darifenacin and oxybutynin ER on memory in older subjects. Eur. Urol. 50(1), 317–326 (2006)

    Article  CAS  PubMed  Google Scholar 

  111. C.A.C. Coupland, T. Hill, T. Dening, R. Morriss, M. Moore, J. Hippisley-Cox, Anticholinergic drug exposure and the risk of dementia: A nested case-control study. JAMA Intern. Med. 179, 1084–1093 (2019)

    Article  PubMed  PubMed Central  Google Scholar 

  112. D. Barthold, Z.A. Marcum, S.L. Gray, J. Zissimopoulos, Alzheimer’s disease and related dementias risk: Comparing users of non-selective and M3-selective bladder antimuscarinic drugs. Pharmacoepidemiol. Drug Saf. 29(12), 1650–1658 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. B. Olshansky, U. Ebinger, J. Brum, M. Egermark, A. Viegas, L. Rekeda, Differential pharmacological effects of antimuscarinic drugs on heart rate: A randomized, placebo-controlled, double-blind, crossover study with tolterodine and darifenacin in healthy participants > or = 50 years. J. Cardiovasc. Pharmacol. Ther. 13, 241–251 (2008)

    Article  CAS  PubMed  Google Scholar 

  114. G.W. Davila, C.A. Daugherty, S.W. Sanders, A short-term, multicenter, randomized double-blind dose titration study of the efficacy and anticholinergic side effects of transdermal compared to immediate release oral oxybutynin treatment of patients with urge urinary incontinence. J. Urol. 166, 140 (2001)

    Article  CAS  PubMed  Google Scholar 

  115. R.R. Dmochowski, V. Nitti, D. Staskin, et al., Transdermal oxybutynin in the treatment of adults with overactive bladder: Combined results of two randomized clinical trials. World J. Urol. 23, 263 (2005)

    Article  CAS  PubMed  Google Scholar 

  116. R. Cartwright, L. Cardozo, Transdermal oxybutynin: Sticking to the facts. Eur. Urol. 51, 907 (2007)

    Article  CAS  PubMed  Google Scholar 

  117. A. Sahai, R. Mallina, C. Dowson, et al., Evolution of transdermal oxybutynin in the treatment of overactive bladder. Int. J. Clin. Pract. 62, 167 (2008)

    Article  CAS  PubMed  Google Scholar 

  118. D.R. Staskin, S. Salvatore, Oxybutynin topical and transdermal formulations: An update. Drugs Today (Barc.) 46, 417–425 (2010)

    Article  CAS  PubMed  Google Scholar 

  119. R. Cartwright, S. Srikrishna, L. Cardozo, et al., Patient-selected goals in overactive bladder: A placebo controlled randomized double-blind trial of transdermaloxybutynin for the treatment of urgency and urge incontinence. BJU Int. 107, 70–76 (2011)

    Article  CAS  PubMed  Google Scholar 

  120. J.M. Gleason, C. Daniels, K. Williams, et al., Single center experience with oxybutynin transdermal system (patch) for management of symptoms related to non-neuropathic overactive bladder in children: An attractive, well tolerated alternative form of administration. J. Pediatr. Urol. 10, 753–757 (2014)

    Article  PubMed  Google Scholar 

  121. D.R. Staskin, R.R. Dmochowski, P.K. Sand, et al., Efficacy and safety of oxybutynin chloride topical gel for overactive bladder: A randomized, double-blind, placebo controlled, multicenter study. J. Urol. 181, 1764–1772 (2009)

    Article  CAS  PubMed  Google Scholar 

  122. D.R. Staskin, D. Robinson, Oxybutynin chloride topical gel: A new formulation of an established antimuscarinic therapy for overactive bladder. Expert. Opin. Pharmacother. 10, 3103–3111 (2009)

    Article  CAS  PubMed  Google Scholar 

  123. R.R. Dmochowski, D.K. Newman, P.K. Sand, et al., Pharmacokinetics of oxybutynin chloride topical gel: Effects of application site, baths, sunscreen and person-to-person transference. Clin. Drug Investig. 31, 559–571 (2011)

    Article  CAS  PubMed  Google Scholar 

  124. P.K. Sand, G.W. Davila, V.R. Lucente, et al., Efficacy and safety of oxybutynin chloride topical gel for women with overactive bladder syndrome. Am. J. Obstet. Gynecol. 206(168), e1–e6 (2012)

    Google Scholar 

  125. M. Fader, S. Glickman, V. Haggar, et al., Intravesical atropine compared to oral oxybutynin for neurogenic detrusor overactivity: A double-blind, randomized crossover trial. J. Urol. 177, 208–213 (2007)

    Article  CAS  PubMed  Google Scholar 

  126. M. Humblet, C. Verpoorten, M.H. Christiaens, et al., Long-term outcome of intravesical oxybutynin in children with detrusor-sphincter dyssynergia: With special reference to age-dependent parameters. Neurourol. Urodyn. 34, 336–342 (2015)

    Article  CAS  PubMed  Google Scholar 

  127. G. Fröhlich, S. Burmeister, A. Wiedemann, et al., Intravesical instillation of trospium chloride, oxybutynin and verapamil for relaxation of the bladder detrusor muscle. A placebo controlled, randomized clinical test. Arzneimittelforschung 48, 486 (1998)

    PubMed  Google Scholar 

  128. P. Walter, J. Grosse, A.M. Bihr, et al., Bioavailability of trospium chloride after intravesical instillation in patients with neurogenic lower urinary tract dysfunction: A pilot study. Neurourol. Urodyn. 18, 447–453 (1999)

    Article  CAS  PubMed  Google Scholar 

  129. K.E. Andersson, W.C. de Groat, K.T. McVary, et al., Tadalafil for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: Pathophysiology and mechanism(s) of action. Neurourol. Urodyn. 30, 292–301 (2011)

    Article  CAS  PubMed  Google Scholar 

  130. F. Giuliano, S. Ückert, M. Maggi, et al., The mechanism of action of phosphodiesterase type 5 inhibitors in the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia. Eur. Urol. 63, 506–516 (2013)

    Article  CAS  PubMed  Google Scholar 

  131. S. Cellek, N.E. Cameron, M.A. Cotter, et al., Microvascular dysfunction and efficacy of PDE5 inhibitors in BPH-LUTS. Nat. Rev. Urol. 11, 231–241 (2014)

    Article  CAS  PubMed  Google Scholar 

  132. D. Behr-Roussel, S. Oger, S. Caisey, et al., Vardenafil decreases bladder afferent nerve activity in unanesthetized, decerebrate, spinal cord-injured rats. Eur. Urol. 59, 272–279 (2010)

    Article  PubMed  Google Scholar 

  133. A. Morelli, S. Filippi, P. Sandner, et al., Vardenafil modulates bladder contractility through cGMP-mediated inhibition of RhoA/rho kinase signaling pathway in spontaneously hypertensive rats. J. Sex. Med. 6, 1594–1608 (2009b)

    Article  CAS  PubMed  Google Scholar 

  134. M. Nomiya, D.M. Burmeister, N. Sawada, et al., Prophylactic effect of tadalafil on bladder function in a rat model of chronic bladder ischemia. J. Urol. 189, 754–761 (2013)

    Article  CAS  PubMed  Google Scholar 

  135. K.T. McVary, C.G. Roehrborn, J.C. Kaminetsky, et al., Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia. J. Urol. 177, 1401–1407 (2007)

    Article  CAS  PubMed  Google Scholar 

  136. C.G. Roehrborn, K.T. McVary, A. Elion-Mboussa, et al., Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: A dose finding study. J. Urol. 180, 1228–1234 (2008)

    Article  CAS  PubMed  Google Scholar 

  137. M. Oelke, F. Giuliano, V. Mirone, et al., Monotherapy with tadalafil or tamsulosin similarly improved lower urinary tract symptoms suggestive of benign prostatic hyperplasia in an international, randomised, parallel, placebo-controlled clinical trial. Eur. Urol. 61, 917–925 (2012)

    Article  CAS  PubMed  Google Scholar 

  138. M. Gacci, K.E. Andersson, C. Chapple, et al., Latest evidence on the use of phosphodiesterase type 5 inhibitors for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. Eur. Urol. 70, 124–133 (2016)

    Article  CAS  PubMed  Google Scholar 

  139. A.P. Cameron, J.Q. Clemens, J.M. Latini, et al., Combination drug therapy improves compliance of the neurogenic bladder. J. Urol. 182, 1062–1067 (2009)

    Article  PubMed  Google Scholar 

  140. M. Gacci, G. Vittori, N. Tosi, et al., A randomized, placebo-controlled study to assess safety and efficacy of vardenafil 10 mg and tamsulosin 0.4 mg vs. tamsulosin 0.4 mg alone in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. J. Sex. Med. 9, 1624–1633 (2012)

    Article  CAS  PubMed  Google Scholar 

  141. R. Dmochowski, C. Roehrborn, S. Klise, et al., Urodynamic effects of once daily tadalafil in men with lower urinary tract symptoms secondary to clinical benign prostatic hyperplasia: A randomized, placebo controlled 12-week clinical trial. J. Urol. 189, S135–S140 (2013)

    Article  CAS  PubMed  Google Scholar 

  142. K.-E. Andersson, Pharmacology of lower urinary tract smooth muscles and penile erectile tissues. Pharmacol. Rev. 45, 253–308 (1993)

    Google Scholar 

  143. A. Nergårdh, L.O. Boréus, A.S. Naglo, Characterization of the adrenergic beta-receptor in the urinary bladder of man and cat. Acta Pharmacol. Toxicol. 40, 14–21 (1977)

    Article  Google Scholar 

  144. J.J. Larsen, Alpha and beta-adrenoceptors in the detrusor muscle and bladder base of the pig and beta-adrenoceptors in the detrusor muscle of man. Br. J. Pharmacol. 65, 215–222 (1979)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. L.J. Emorine, S. Marullo, M.M. Briend-Sutren, et al., Molecular characterization of the human beta 3-adrenergic receptor. Science 245, 1118–1121 (1989)

    Article  CAS  PubMed  Google Scholar 

  146. Y. Igawa, M.C. Michel, Pharmacological profile of β3-adrenoceptor agonists in clinical development for the treatment of overactive bladder syndrome. Naunyn Schmiedeberg’s Arch. Pharmacol. 386, 177–183 (2013)

    Article  CAS  Google Scholar 

  147. Y. Igawa, Y. Yamazaki, H. Takeda, et al., Functional and molecular biological evidence for a possible beta3-adrenoceptor in the human detrusor muscle. Br. J. Pharmacol. 126, 819–825 (1999)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. M. Takeda, K. Obara, T. Mizusawa, 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. 288, 1367–1373 (1999)

    CAS  PubMed  Google Scholar 

  149. K. Fujimura, K. Tamura, T. Tsutsumi, et al., Expression and possible functional role of the beta3-adrenoceptor in human and rat detrusor muscle. J. Urol. 161, 680–685 (1999)

    Article  CAS  PubMed  Google Scholar 

  150. A. Otsuka, H. Shinbo, R. Matsumoto, et al., Expression and functional role of beta-adrenoceptors in the human urinary bladder urothelium. Naunyn Schmiedeberg's Arch. Pharmacol. 377, 473–481 (2008)

    Article  CAS  Google Scholar 

  151. M. Nomiya, O. Yamaguchi, A quantitative analysis of mRNA expression of alpha 1 and beta-adrenoceptor subtypes and their functional roles in human normal and obstructed bladders. J. Urol. 170, 649–653 (2003)

    Article  CAS  PubMed  Google Scholar 

  152. Y. Igawa, Y. Yamazaki, H. Takeda, et al., Relaxant effects of isoproterenol and selective beta3-adrenoceptor agonists on normal, low compliant and hyperreflexic human bladders. J. Urol. 165, 240–244 (2001)

    Article  CAS  PubMed  Google Scholar 

  153. Y. Igawa, N. Aizawa, Y. Homma, Beta3-adrenoceptor agonists: Possible role in the treatment of overactive bladder. Korean J. Urol. 51, 811–818 (2010)

    Article  PubMed  PubMed Central  Google Scholar 

  154. M.C. Michel, W. Vrydag, Alpha1-, alpha2- and beta-adrenoceptors in the urinary bladder, urethra and prostate. Br. J. Pharmacol. 147, S88–S119 (2006)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. D. Hudman, R.A. Elliott, R.I. Norman, K(ATP) channels mediate the beta(2)-adrenoceptor agonist-induced relaxation of rat detrusor muscle. Eur. J. Pharmacol. 397, 169–176 (2000)

    Article  CAS  PubMed  Google Scholar 

  156. E.P. Frazier, M.J. Mathy, S.L. Peters, et al., Does cyclic AMP mediate rat urinary bladder relaxation by isoproterenol? J. Pharmacol. Exp. Ther. 313, 260–266 (2005)

    Article  CAS  PubMed  Google Scholar 

  157. E.P. Frazier, S.L.M. Peters, A.S. Braverman, et al., Signal transduction underlying control of urinary bladder smooth muscle tone by muscarinic receptors and β-adrenoceptors. Naunyn Schmiedeberg’s Arch. Pharmacol. 377, 449–462 (2008)

    Article  CAS  Google Scholar 

  158. H. Uchida, K. Shishido, M. Nomiya, et al., Involvement of cyclic AMP-dependent and -independent mechanisms in the relaxation of rat detrusor muscle via beta-adrenoceptors. Eur. J. Pharmacol. 518, 195–202 (2005)

    Article  CAS  PubMed  Google Scholar 

  159. S.M. Biers, J.M. Reynard, A.F. Brading, The effects of a new selective beta3-adrenoceptor agonist (GW427353) on spontaneous activity and detrusor relaxation in human bladder. BJU Int. 98, 1310–1314 (2006)

    Article  CAS  PubMed  Google Scholar 

  160. T. Takasu, M. Ukai, S. Sato, et al., Effect of (R)-2-(2-aminothiazol 4-yl)-4′-{2-[(2-hydroxy-2-phenylethyl) amino]ethyl}acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladder function. J. Pharmacol. Exp. Ther. 321, 642–647 (2007)

    Article  CAS  PubMed  Google Scholar 

  161. N. Aizawa, Y. Homma, Y. Igawa, Effects of mirabegron, a novel β3-adrenoceptor agonist, on primary bladder afferent activity and bladder microcontractions in rats compared with the effects of oxybutynin. Eur. Urol. 62, 1165–1173 (2012)

    Article  CAS  PubMed  Google Scholar 

  162. J.I. Gillespie, S. Palea, V. Guilloteau, et al., Modulation of non-voiding activity by the muscarinic antagonist tolterodine and the β(3)-adrenoceptor agonist mirabegron in conscious rats with partial outflow obstruction. BJU Int. 110, E132–E142 (2012)

    Article  CAS  PubMed  Google Scholar 

  163. T. Hatanaka, M. Ukai, M. Watanabe, et al., In vitro and in vivo pharmacological profile of the selective β3-adrenoceptor agonist mirabegron in rats. Naunyn Schmiedeberg’s Arch. Pharmacol. 386, 247–253 (2013)

    Article  CAS  Google Scholar 

  164. M.C. Michel, Y. Igawa, Therapeutic targets for overactive bladder other than smooth muscle. Expert Opin. Ther. Targets 19, 687–705 (2015)

    Article  CAS  PubMed  Google Scholar 

  165. C. Rouget, M. Rekik, P. Camparo, et al., Modulation of nerve-evoked contractions by β3-adrenoceptor agonism in human and rat isolated urinary bladder. Pharmacol. Res. 80, 14–20 (2014)

    Article  CAS  PubMed  Google Scholar 

  166. G. D’Agostino, A.M. Condino, P. Calvi, Involvement of β-adrenoceptors in the inhibitory control 3 of cholinergic activity in human bladder: Direct evidence 3 by [H]-acetylcholine release experiments in the isolated detrusor. Eur. J. Pharmacol. 758, 115–122 (2015)

    Article  PubMed  Google Scholar 

  167. L.A. Birder, M.L. Nealen, S. Kiss, et al., Beta-adrenoceptor agonists stimulate endothelial nitric oxide synthase in rat urinary bladder urothelial cells. J. Neurosci. 22, 8063–8070 (2002)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. S. Murakami, C.R. Chapple, H. Akino, et al., The role of the urothelium in mediating bladder responses to isoprenaline. BJU Int. 99, 669–673 (2007)

    Article  CAS  PubMed  Google Scholar 

  169. K. Masunaga, C.R. Chapple, N.G. McKay, et al., The β3-adrenoceptor mediates the inhibitory effects of β-adrenoceptor agonists via the urothelium in pig bladder dome. Neurourol. Urodyn. 29, 1320–1325 (2010)

    Article  CAS  PubMed  Google Scholar 

  170. M. Woods, N. Carson, N.W. Norton, J.H. Sheldon, T.M. Argentieri, Efficacy of the beta3-adrenergic receptor agonist CL-316243 on experimental bladder hyperreflexia and detrusor instability in the rat. J. Urol. 166, 1142–1147 (2001)

    Article  CAS  PubMed  Google Scholar 

  171. H. Takeda, Y. Yamazaki, Y. Igawa, et al., Effects of beta(3)-adrenoceptor stimulation on prostaglandin E(2)-induced bladder hyperactivity and on the cardiovascular system in conscious rats. Neurourol. Urodyn. 21, 558–565 (2002)

    Article  CAS  PubMed  Google Scholar 

  172. K. Kaidoh, Y. Igawa, H. Takeda, et al., Effects of selective beta2 and beta3-adrenoceptor agonists on detrusor hyperreflexia in conscious cerebral infarcted rats. J. Urol. 168, 1247–1252 (2002)

    Article  CAS  PubMed  Google Scholar 

  173. A. Hicks, G.P. McCafferty, E. Riedel, et al., GW427353 (solabegron), a novel, selective beta3-adrenergic receptor agonist, evokes bladder relaxation and increases micturition reflex threshold in the dog. J. Pharmacol. Exp. Ther. 323, 202–209 (2007)

    Article  CAS  PubMed  Google Scholar 

  174. T. Takasu, M. Ukai, S. Sato, et al., Effect of(R)-2-(2-aminothiazol-4-yl)-4′-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl} acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladderfunction. J. Pharmacol. Exp. Ther. 321(2), 642–647 (2007 May)

    Article  CAS  PubMed  Google Scholar 

  175. C. Eltink, J. Lee, M. Schaddelee, et al., Single dose pharmacokinetics and absolute bioavailibility of mirabegron, a β3-adrenoceptor agonist for treatment of overactive bladder. Int. J. Clin. Pharmacol. Ther. 50, 838–850 (2012)

    Article  CAS  PubMed  Google Scholar 

  176. W. Krauwinkel, J. van Dijk, M. Schaddelee, et al., Pharmacokinetic properties of mirabegron, a β(3)-adrenoceptor agonist: Results from two phase I, randomized, multiple-dose studies in healthy young and elderly men and women. Clin. Ther. 34, 2144–2160 (2012)

    Article  CAS  PubMed  Google Scholar 

  177. S. Takusagawa, J.J. van Lier, K. Suzuki, et al., Absorption, metabolism and excretion of [(14)C]mirabegron (YM178), a potent and selective β(3)-adrenoceptor agonist, after oral administration to healthy male volunteers. Drug Metab. Dispos. 40, 815–824 (2012)

    Article  CAS  PubMed  Google Scholar 

  178. C. Füllhase, R. Soler, K. Westerling-Andersson, K.E. Andersson, Beta3- adrenoceptors in the rat sacral spinal cord and their functional relevance in micturition under normal conditions and in a model of partial urethral obstruction. Neurourol. Urodyn. 30, 1382–1387 (2011)

    Article  PubMed  Google Scholar 

  179. S. Takusagawa, K. Yajima, A. Miyashita, et al., Identification of human cytochrome P450 isoforms and esterases involved in the metabolism of mirabegron, a potent and selective β(3)- adrenoceptor agonist. Xenobiotica 42, 957–967 (2012b)

    Article  CAS  PubMed  Google Scholar 

  180. S. Takusagawa, A. Miyashita, T. Iwatsubo, et al., In vitro inhibition and induction of human cytochrome P450 enzymes by mirabegron, a potent and selective β3-adrenoceptor agonist. Xenobiotica 42, 1187–1196 (2012c)

    Article  CAS  PubMed  Google Scholar 

  181. J. Lee, S. Moy, J. Meijer, et al., Role of cytochrome p450 isoenzymes 3A and 2D6 in the in vivo metabolism of mirabegron, a β3-adrenoceptor agonist. Clin. Drug Investig. 33(6), 429–440 (2013)

    Article  CAS  PubMed  Google Scholar 

  182. C.R. Chapple, L. Cardozo, V.W. Nitti, et al., Mirabegron in overactive bladder: A review of efficacy, safety, and tolerability. Neurourol. Urodyn. 33, 17–30 (2014)

    Article  CAS  PubMed  Google Scholar 

  183. Y. Cui, H. Zong, C. Yang, et al., The efficacy and safety of mirabegron in treating OAB: A systematic review and meta-analysis of phase III trials. Int. Urol. Nephrol. 46, 275–284 (2014)

    Article  CAS  PubMed  Google Scholar 

  184. M. Rossanese, G. Novara, B. Challacombe, et al., Critical analysis of phase II and III randomised control trials (RCTs) evaluating efficacy and tolerability of a β3-adrenoceptor agonist (Mirabegron) for overactive bladder (OAB). BJU Int. 115, 32–40 (2015)

    Article  CAS  PubMed  Google Scholar 

  185. O. Suarez, D. Osborn, M. Kaufman, et al., Mirabegron for male lower urinary tract symptoms. Curr. Urol. Rep. 14, 580–584 (2013)

    Article  PubMed  Google Scholar 

  186. H. Otsuki, T. Kosaka, K. Nakamura, et al., β3-Adrenoceptor agonist mirabegron is effective for overactive bladder that is unresponsive to antimuscarinic treatment or is related to benign prostatic hyperplasia in men. Int. Urol. Nephrol. 45, 53–60 (2013)

    Article  CAS  PubMed  Google Scholar 

  187. P. Abrams, C. Kelleher, D. Staskin, Combination treatment with mirabegron and solifenacin in patients with overactive bladder: Efficacy and safety results from a randomised, double-blind, dose-ranging, phase 2 study (Symphony). Eur. Urol. 67, 577–588 (2015)

    Article  CAS  PubMed  Google Scholar 

  188. S. Herschorn, C.R. Chapple, P. Abrams, S. Arlandis, D. Mitcheson, K.S. Lee, A. Ridder, M. Stoelzel, A. Paireddy, R. van Maanen, D. Robinson, Efficacy and safety of combinations of mirabegron and solifenacin compared with monotherapy and placebo in patients with overactive bladder (SYNERGY study). BJU Int. 120(4), 562–575 (2017 Oct)

    Article  CAS  PubMed  Google Scholar 

  189. D. Robinson, C. Kelleher, D. Staskin, et al., Patient-reported outcomes from SYNERGY, a randomized, double-blind, multicenter study evaluating combinations of mirabegron and solifenacin compared with monotherapy and placeboin OAB patients. Neurourol. Urodyn. 37(1), 394–406 (2018 Jan)

    Article  CAS  PubMed  Google Scholar 

  190. M.J. Drake, C. Chapple, A.A. Esen, S. Athanasiou, J. Cambronero, D. Mitcheson, S. Herschorn, T. Saleem, M. Huang, E. Siddiqui, M. Stölzel, C. Herholdt, S. MacDiarmid, BESIDE study investigators. Efficacy and safety of Mirabegron add-on therapy to Solifenacin in incontinent overactive bladder patients with an inadequate response to initial 4-week Solifenacin monotherapy: A randomised double-blind multicentre phase 3B study (BESIDE). Eur. Urol. 70(1), 136–145 (2016, July)

    Article  CAS  PubMed  Google Scholar 

  191. C. Gratzke, R. van Maanen, C. Chapple, et al., Long-term safety and efficacy of Mirabegron and Solifenacin in combination compared with monotherapy in patients with overactive bladder: A randomised, multicentre phase 3 study (SYNERGY II). Eur. Urol. 74(4), 501–509 (2018, October)

    Article  CAS  PubMed  Google Scholar 

  192. O. Yamaguchi, H. Kakizaki, Y. Homma, Y. Igawa, M. Takeda, O. Nishizawa, M. Gotoh, M. Yoshida, O. Yokoyama, N. Seki, A. Okitsu, T. Hamada, A. Kobayashi, K. Kuroishi, Long-term safety and efficacy of antimuscarinic add-on therapy in patients with overactive bladder who had a suboptimal response to mirabegron monotherapy: A multicenter, randomized study in Japan (MILAI II study). Int. J. Urol. 26(3), 342–352 (2019)

    Article  CAS  PubMed  Google Scholar 

  193. Y. Matsukawa, S. Takai, T. Majima, Y. Funahashi, N. Sassa, M. Kato, T. Yamamoto, M. Gotoh, Comparison in the efficacy of fesoterodine or mirabegron add-on therapy to silodosin for patients with benign prostatic hyperplasia complicated by overactive bladder: A randomized, prospective trial using urodynamic studies. Neurourol. Urodyn. 38(3), 941–949 (2019)

    Article  CAS  PubMed  Google Scholar 

  194. H. Kakizaki, K.S. Lee, O. Yamamoto, J.J. Jong, D. Katou, B. Sumarsono, S. Uno, O. Yamaguchi, Mirabegron add-on therapy to Tamsulosin for the treatment of overactive bladder in men with lower urinary tract symptoms: A randomized, placebo-controlled study (MATCH). Eur. Urol. Focus 6(4), 729–737 (2020, July 15)

    Article  PubMed  Google Scholar 

  195. J. Wöllner, J. Pannek, Initial experience with the treatment of neurogenic detrusor overactivity with a new β-3 agonist (mirabegron) in patients with spinalcord injury. Spinal Cord 54, 78–82 (2016)

    Article  PubMed  Google Scholar 

  196. J. Krhut, V. Borovička, K. Bílková, R. Sýkora, D. Míka, J. Mokriš, R. Zachoval, Efficacy and safety of mirabegron for the treatment of neurogenic detrusor overactivity-prospective, randomized, double-blind, placebo-controlled study. Neurourol. Urodyn. 37(7), 2226–2233 (2018)

    Article  CAS  PubMed  Google Scholar 

  197. A.S. Blais, G. Nadeau, K. Moore, L. Genois, S. Bolduc, Prospective pilot study of Mirabegron in Pediatric patients with overactive bladder. Eur. Urol. 70(1), 9–13 (2016)

    Article  PubMed  Google Scholar 

  198. S. Fryer, C. Nicoara, E. Dobson, M. Griffiths, H.F. McAndrew, S.E. Kenny, H.J. Corbett, Effectiveness and tolerability of mirabegron in children with overactive bladder: A retrospective pilot study. J. Pediatr. Surg. 55(2), 316–318 (2020)

    Article  PubMed  Google Scholar 

  199. M. Baka-Ostrowska, D.T. Bolong, C. Persu, C. Tøndel, A. Steup, C. Lademacher, N. Martin, Efficacy and safety of mirabegron in children and adolescents with neurogenic detrusor overactivity: An open-label, phase 3, dose-titration study. Neurourol. Urodyn. (2021, May 31). https://doi.org/10.1002/nau.24657. Epub ahead of print

  200. J.S. Park, Y.S. Lee, C.N. Lee, S.H. Kim, S.W. Kim, S.W. Han, 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. 37(8), 1665–1670 (2019)

    Article  CAS  PubMed  Google Scholar 

  201. S.D. Edmondson, C. Zhu, N.F. Kar, et al., Discovery of Vibegron: A potent and selective β3 adrenergic receptor agonist for the treatment of overactive bladder. J. Med. Chem. 59(2), 609–623 (2016)

    Article  CAS  PubMed  Google Scholar 

  202. M. Yoshida, M. Takeda, M. Gotoh, S. Nagai, T. Kurose, Vibegron, a novel potent and selective beta3-Adrenoreceptor agonist, for the treatment of patients with overactive bladder: A randomized, double-blind, placebo-controlled phase 3 study. Eur. Urol. 73, 783–790 (2018)

    Article  CAS  PubMed  Google Scholar 

  203. M. Yoshida, H. Kakizaki, S. Takahashi, S. Nagai, T. Kurose, Long-term safety and efficacy of the novel beta3 -adrenoreceptor agonist vibegron in Japanese patients with overactive bladder: A phase III prospective study. Int. J. Urol. 25, 668–675 (2018)

    Article  CAS  PubMed  Google Scholar 

  204. M. Yoshida, M. Takeda, M. Gotoh, et al., Efficacy of vibegron, a novel β3-adrenoreceptor agonist, on severe urgency urinary incontinence related to overactive bladder: Post hoc analysis of a randomized, placebo-controlled, double-blind, comparative phase 3 study. BJU Int. 125(5), 709–717 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  205. H.D. Mitcheson, S. Samanta, K. Muldowney, et al., Vibegron (RVT-901/MK-4618/KRP-114V) administered once daily as monotherapy or concomitantly with Tolterodine in patients with an overactive bladder: A multicenter, phase IIb, randomized, double-blind, controlled trial. Eur. Urol. 75(2), 274–282 (2019)

    Article  CAS  PubMed  Google Scholar 

  206. D. Staskin, J. Frankel, S. Varano, D. Shortino, R. Jankowich, P.N. Mudd Jr., International phase III, randomized, double-blind, placebo and active controlled study to evaluate the safety and efficacy of Vibegron in patients with symptoms of overactive bladder: EMPOWUR. J. Urol. 204(2), 316–324 (2020)

    Article  PubMed  Google Scholar 

  207. D. Staskin, J. Frankel, S. Varano, et al., Once-daily Vibegron 75 mg for overactive bladder: Long-term safety and efficacy from a double-blind extension study of the international phase 3 trial (EMPOWUR). J. Urol. 205(5), 1421–1429 (2021)

    Article  PubMed  Google Scholar 

  208. S. Varano, D. Staskin, J. Frankel, et al., Efficacy and safety of once-daily Vibegron for treatment of overactive bladder in patients aged ≥65 and ≥75 years: Subpopulation analysis from the EMPOWUR randomized, international, phase III study. Drugs Aging 38(2), 137–146 (2021)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Frankel J, Varano S, Staskin D, et al. Vibegron improves quality-of-life measures in patients with overactive bladder: Patient-reported outcomes from the EMPOWUR study. Int. J. Clin. Pract. 2020, December 17:e13937. https://doi.org/10.1111/ijcp.13937. Online ahead of print

  210. G. Thiagamoorthy, I. Giarenis, L. Cardozo, Early investigational β3 adreno-receptor agonists for the management of the overactive bladder syndrome. Expert Opin. Investig. Drugs 24, 1299–1306 (2015)

    Article  CAS  PubMed  Google Scholar 

  211. G. Thiagamoorthy, L. Cardozo, D. Robinson, Current and future pharmacotherapy for treating overactive bladder. Expert. Opin. Pharmacother. 17, 1317–1325 (2016)

    Article  CAS  PubMed  Google Scholar 

  212. E.H. Ohlstein, A. von Keitz, M.C. Michel, A multicenter, double-blind, randomized, placebo-controlled trial of the β3-adrenoceptor agonist solabegron for overactive bladder. Eur. Urol. 62, 834–840 (2012)

    Article  CAS  PubMed  Google Scholar 

  213. N. Abo Youssef, M.P. Schneider, L. Mordasini, B.V. Ineichen, L.M. Bachmann, E. Chartier-Kastler, et al., Cannabinoids for treating neurogenic lower urinary tract dysfunction in patients with multiple sclerosis: A systematic review and meta-analysis. BJU Int. 119(4), 515–521 (2017)

    Article  PubMed  Google Scholar 

  214. S. Adhikary, H. Li, J. Heller, M. Skarica, M. Zhang, D. Ganea, et al., Modulation of inflammatory responses by a cannabinoid-2-selective agonist after spinal cord injury. J. Neurotrauma 28, 2417–2427 (2011)

    Article  PubMed  PubMed Central  Google Scholar 

  215. N. Aizawa, P. Hedlund, C. Füllhase, et al., Inhibition of peripheral FAAH depresses activities of bladder mechanosensitive nerve fibers of the rat. J. Urol. 192(3), 956–963 (2014, September)

    Article  CAS  PubMed  Google Scholar 

  216. K.E. Andersson, Potential future pharmacological treatment of bladder dysfunction. Basic Clin. Pharmacol. Toxicol. 119(Suppl 3), 75–85 (2016, October)

    Article  CAS  PubMed  Google Scholar 

  217. E. Bakali, R.A. Elliott, A.H. Tayloer, D.G. Lambert, J.M. Willets, D.G. Tincello, Human urothelial cell lines as potential models for studying cannabinoid and excitatory receptor interactions in the urinary bladder. Naunyn Schmiedeberg’s Arch. Pharmacol. 387(6), 581–589 (2014)

    Article  CAS  Google Scholar 

  218. D.E. Björling, Z.-Y. Wang, Potential of endocannabinoids to control bladder pain. Front. Syst. Neurosci. 12, 17 (2018, May 15)

    Article  PubMed  PubMed Central  Google Scholar 

  219. C.M. Brady, R. DasGupta, C. Dalton, O.J. Wiseman, K.J. Berkley, C.J. Fowler, An open-label pilot study of cannabis-based extracts for bladder dysfunction in advanced multiple sclerosis. Mult. Scler. 10(4), 425–433 (2004)

    Article  CAS  PubMed  Google Scholar 

  220. J.L. Capodice, S.A. Kaplan, The endocannabinoid system, cannabis, and cannabidiol: Implications in urology and men’s health. Curr Urol. 15(2), 95–100 (2021, June)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  221. A. Charrua, R. Matos, R. Oliveira, T. Marczylo, I. Nagy, F. Cruz, Fatty acid amide hydrolase inhibition normalises bladder function and reduces pain through normalising the anandamide/palmitoylethanolamine ratio in the inflamed bladder of rats. Naunyn Schmiedeberg’s Arch. Pharmacol. 393(2), 263–272 (2020)

    Article  CAS  Google Scholar 

  222. S. Christie, S. Brookes, V. Zagorodnyuk, Endocannabinoids in bladder sensory mechanisms in health and diseases. Front. Pharmacol. 12, 708989 (2021, July 5)

    Article  PubMed  PubMed Central  Google Scholar 

  223. L. Cristino, T. Becker, V. Di Marzo, Endocannabinoids and energy homeostasis: An update. Biofactors 40, 389–397 (2014)

    Article  CAS  PubMed  Google Scholar 

  224. W.P. Farquhar-Smith, A.S. Rice, Administration of endocannabinoids prevents a referred hyperalgesia associated with inflammation of the urinary bladder. Anesthesiology 94, 507–513 (2001)

    Article  CAS  PubMed  Google Scholar 

  225. D.P. Finn, S. Haroutounian, A.G. Hohmann, et al., Cannabinoids, the endocannabinoid system, and pain: a review of preclinical studies. Pain (2021) PMID: 33729211

    Google Scholar 

  226. R.M. Freeman, O. Adekanmi, M.R. Waterfield, A.E. Waterfield, D. Wright, J. Zajicek, The effect of cannabis on urge incontinence in patients with multiple sclerosis: A multicentre, randomised placebo-controlled trial (CAMS-LUTS). Int. Urogynecol. J. 17(6), 636–641 (2006)

    Article  CAS  Google Scholar 

  227. C. Gratzke, T. Streng, A. Park, G. Christ, C.G. Stief, P. Hedlund, et al., Distribution and function of cannabinoid receptors 1 and 2 in the rat, monkey and human bladder. J. Urol. 181, 1939–1948 (2009)

    Article  CAS  PubMed  Google Scholar 

  228. C. Gratzke, T. Streng, C.G. Stief, T.R. Downs, I. Alroy, J.S. Rosenbaum, et al., Effects of cannabinor, a novel selective cannabinoid 2 receptor agonist, on bladder function in normal rats. Eur. Urol. 57, 1093–1100 (2010)

    Article  CAS  PubMed  Google Scholar 

  229. C. Gratzke, T. Streng, C.G. Stief, I. Alroy, B.J. Limberg, T.R. Downs, et al., Cannabinor, a selective cannabinoid-2 receptor agonist, improves bladder emptying in rats with partial urethral obstruction. J. Urol. 185, 731–736 (2011)

    Article  CAS  PubMed  Google Scholar 

  230. P. Hedlund, C. Gratzke, The endocannabinoid system – A target for the treatment of LUTS? Nat. Rev. Urol. 13(8), 463–470 (2016, August)

    Article  CAS  PubMed  Google Scholar 

  231. S.I. Jaggar, F.S. Hasnie, S. Sellaturay, A.S. Rice, The anti-hyperalgesic actions of the cannabinoid anandamide and the putative CB2 receptor agonist palmitoylethanolamide in visceral and somatic inflammatory pain. Pain 76, 189–199 (1998)

    Article  CAS  PubMed  Google Scholar 

  232. R.B. Kavia, D. De Ridder, C.S. Constantinescu, C.G. Stott, C.J. Fowler, Randomized controlled trial of Sativex to treat detrusor overactivity in multiple sclerosis. Mult. Scler. 16(11), 1349–1359 (2010)

    Article  CAS  PubMed  Google Scholar 

  233. G. Mukerji, Y. Yiangou, S.K. Agarwal, et al. Increased cannabinoid receptor 1-immunoreactive nerve fibers in overactive and painful bladder disorders and their correlation with symptoms. Urology 75(6), 1514.e15–1514.e20 (2010, June)

    Google Scholar 

  234. K.J. Nabata, K. Emmanuel, E.K. Tse, E. Tom, T.E. Nightingale, et al., The therapeutic potential and usage patterns of cannabinoids in people with spinal cord injuries: A systematic review. Curr. Neuropharmacol. 19(3), 402–432 (2021 Mar)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  235. P. Pacher, S. Steffens, The emerging role of the endocannabinoid system in cardiovascular disease. Semin. Immunopathol. 31, 63–77 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  236. C. Saitoh, C. Kitada, W. Uchida, M.B. Chancellor, W.C. de Groat, N. Yoshimura, The differential contractile responses to capsaicin and anandamide in muscle strips isolated from the rat urinary bladder. Eur. J. Pharmacol. 570, 182–187 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  237. F. Strittmatter, G. Gandaglia, Benigni, et al., Expression of fatty acid amide hydrolase (FAAH) in human, mouse, and rat urinary bladder and effects of FAAH inhibition on bladder function in awake rats. Eur. Urol. 61(1), 98–106 (2012, January)

    Article  CAS  PubMed  Google Scholar 

  238. I. Svízenská, P. Dubový, A. Sulcová, Cannabinoid receptors 1 and 2 (CB1 and CB2), their distribution, ligands and functional involvement in nervous system structures–A short review. Pharmacol. Biochem. Behav. 90(4), 501–511 (2008, October)

    Article  PubMed  Google Scholar 

  239. C. Taylor, B. Birch, Cannabinoids in urology. Which benign conditions might they be appropriate to treat: A systematic review. Urology 148, 8–25 (2021, February)

    Article  CAS  PubMed  Google Scholar 

  240. M.C. Torres-Moreno, E. Papaseit, M. Torrens, M. Farré, Assessment of efficacy and tolerability of medicinal cannabinoids in patients with multiple sclerosis: A systematic review and meta-analysis. JAMA Netw. Open 1(6), e183485 (2018)

    Article  PubMed  PubMed Central  Google Scholar 

  241. R.K.P. Tripathi, A perspective review on fatty acid amide hydrolase (FAAH) inhibitors as potential therapeutic agents. Eur Med Chem. 15(188), 111953 (2020, February)

    Article  Google Scholar 

  242. S. Vuckovic, D. Srebro, K.S. Vujovic, et al., Cannabinoids and pain: New insights from old molecules. Front. Pharmacol. 9, 1259 (2018, November 13)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  243. D.T. Wade, P. Makela, P. Robson, et al., Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients. Mult. Scler. 10(4), 434–441 (2004, August)

    Article  CAS  PubMed  Google Scholar 

  244. F.M.E. Wagenlehner, J.W.O. van Till, J.G.A. Houbiers, et al., Fatty acid amide hydrolase inhibitor treatment in men with chronic prostatitis/chronic pelvic pain syndrome: An adaptive double-blind, randomized controlledmtrial. Urology 103, 191–197 (2017)

    Article  PubMed  Google Scholar 

  245. J.S. Walczak, F. Cervero, Local activation of cannabinoid CB1 receptors in the urinary bladder reduces the inflammation-induced sensitization of bladder afferents. Mol. Pain 7, 31 (2011, May 9)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  246. Z.-Y. Wang, P. Wang, C.J. Hillard, D.E. Bjorling, Attenuation of cystitis and pain sensation in mice lacking fatty acid amide hydrolase. J. Mol. Neurosci. 55(4), 968–976 (2015a)

    Article  CAS  PubMed  Google Scholar 

  247. Z.-Y. Wang, P. Wang, D.E. Bjorling, Activation of cannabinoid receptor 1 inhibits increased bladder activity induced by nerve growth factor. Neurosci. Lett. 589, 19–24 (2015b)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  248. Z.Y. Wang, P. Wang, D.E. Bjorling, Activation of cannabinoid receptor 2 inhibits experimental cystitis. Am. J. Physiol. Regul. Integr. Comp. Physiol. 304, R846–R853 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  249. P.M. Zygmunt, J. Petersson, D.A. Andersson, et al., Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 400, 452–457 (1999)

    Article  CAS  PubMed  Google Scholar 

  250. P. Abrams, G. Amarenco, A. Bakke, et al., European Tamsulosin neurogenic lower urinary tract dysfunction study group. Tamsulosin: Efficacy and safety in patients with neurogenic lower urinary tract dysfunction due to suprasacral spinal cord injury. J. Urol. 170, 1242–1251 (2003)

    Article  PubMed  Google Scholar 

  251. A.P. Cameron, Medical management of neurogenic bladder with oral therapy. Transl. Androl. Urol. 5, 51–62 (2016)

    PubMed  PubMed Central  Google Scholar 

  252. K.E. Andersson, C. Gratzke, Pharmacology of alpha1-adrenoceptor antagonists in the lower urinary tract and central nervous system. Nat. Clin. Pract. Urol. 4, 368–378 (2007)

    Article  CAS  PubMed  Google Scholar 

  253. K.H. Moon, C.H. Park, H.C. Jung, et al., A 12-week, open label, multi-center study to evaluate the clinical efficacy and safety of silodosin on voiding dysfunction in patients with neurogenic bladder. Low Urin Tract. Symptoms. 7, 27–31 (2015)

    Article  CAS  PubMed  Google Scholar 

  254. S.J. Swierzewski 3rd, E.A. Gormley, W.D. Belville, et al., The effect of terazosin on bladder function in the spinal cord injured patient. J. Urol. 151, 951–954 (1994)

    Article  PubMed  Google Scholar 

  255. K. Yasuda, T. Yamanishi, K. Kawabe, H. Ohshima, T. Morita, The effect of urapidil on neurogenic bladder: A placebo controlled double-blind study. J. Urol. 156, 1125–1130 (1996)

    Article  CAS  PubMed  Google Scholar 

  256. J.I. O'Riordan, C. Doherty, M. Javed, et al., Do alpha-blockers have a role in lower urinary tract dysfunction in multiple sclerosis? J. Urol. 153, 1114–1116 (1995)

    Article  CAS  PubMed  Google Scholar 

  257. H. Kakizaki, K. Ameda, S. Kobayashi, et al., Urodynamic effects of alpha1-blocker tamsulosin on voiding dysfunction in patients with neurogenic bladder. Int. J. Urol. 10, 576–581 (2003)

    Article  CAS  PubMed  Google Scholar 

  258. H. Krum, W.J. Louis, D.J. Brown, et al., A study of the alpha-1 adrenoceptor blocker prazosin in the prophylactic management of autonomic dysreflexia in high spinal cord injury patients. Clin. Auton. Res. 2, 83–88 (1992)

    Article  CAS  PubMed  Google Scholar 

  259. M.B. Chancellor, M.J. Erhard, I.H. Hirsch, et al., Prospective evaluation of terazosin for the treatment of autonomic dysreflexia. J. Urol. 151, 111–113 (1994)

    Article  CAS  PubMed  Google Scholar 

  260. A.A. Phillips, S.L. Elliott, M.M. Zheng, et al., Selective alpha adrenergic antagonist reduces severity of transient hypertension during sexual stimulation after spinal cord injury. J. Neurotrauma 15(32), 392–396 (2015)

    Article  Google Scholar 

  261. J.C. Nickel, S. Sander, T.D. Moon, A meta-analysis of the vascular-related safety profile and efficacy of alpha-adrenergic blockers for symptoms related to benign prostatic hyperplasia. Int. J. Clin. Pract. 62, 1547–1559 (2008)

    Article  CAS  PubMed  Google Scholar 

  262. M. Oelke, A. Gericke, M.C. Michel, Cardiovascular and ocular safety of α1-adrenoceptor antagonists in the treatment of male lower urinary tract symptoms. Expert Opin. Drug Saf. 13, 1187–1197 (2014)

    Article  CAS  PubMed  Google Scholar 

  263. W.C. de Groat, A neurologic basis for the overactive bladder. Urology 50, 36–52 (1997)

    Article  PubMed  Google Scholar 

  264. M.C. Taylor, C.P. Bates, A double-blind crossover trial of baclofen–a new treatment for the unstable bladder syndrome. Br. J. Urol. 51, 504 (1979)

    Article  CAS  PubMed  Google Scholar 

  265. G.A. Ochs, Intrathecal baclofen. Baillieres Clin. Neurol. 2, 73–86 (1993)

    CAS  PubMed  Google Scholar 

  266. W. Bushman, W.D. Steers, J.M. Meythaler, Voiding dysfunction in patients with spastic paraplegia: Urodynamic evaluation and response to continuous intrathecal baclofen. Neurourol. Urodyn. 12, 163 (1993)

    Article  CAS  PubMed  Google Scholar 

  267. S. Szollar, J. North, J. Chung, Antidiuretic hormone levels and polyuria in spinal cord injury. A preliminary report. Paraplegia 33, 94–97 (1995)

    CAS  PubMed  Google Scholar 

  268. A. Zahariou, G. Karagiannis, P. Papaioannou, et al., The use of desmopressin in the management of nocturnal enuresis in patients with spinal cord injury. Eura. Medicophys. 43, 333–338 (2007)

    CAS  PubMed  Google Scholar 

  269. M. Horowitz, A.J. Combs, D. Gerdes, Desmopressin for nocturnal incontinence in the spina bifida population. J. Urol. 158, 2267–2268 (1997)

    Article  CAS  PubMed  Google Scholar 

  270. R. Del Gado, G. Aceto, D. Del Gaizo, et al., Desmopressin for the treatment of nocturnal bedwetting in patients with neural tube closure defects. J. Urol. 171, 1656–1658 (2004)

    Article  PubMed  Google Scholar 

  271. M.B. Chancellor, D.A. Rivas, W.E. Staas Jr., DDAVP in the urological management of the difficult neurogenic bladder in spinal cord injury: Preliminary report. J. Am. Paraplegia Soc. 17, 165–167 (1994)

    Article  CAS  PubMed  Google Scholar 

  272. R. Bosma, K. Wynia, E. Havlíková, et al., Efficacy of desmopressin in patients with multiple sclerosis suffering from bladder dysfunction: A meta-analysis. Acta Neurol. Scand. 112, 1–5 (2005)

    Article  CAS  PubMed  Google Scholar 

  273. G. Valiquette, J. Herbert, P. Maede-D’Alisera, Desmopressin in the management of nocturia in patients with multiple sclerosis. A double-blind, crossover trial. Arch. Neurol. 53, 1270–1275 (1996)

    Article  CAS  PubMed  Google Scholar 

  274. K.E. Andersson, A. Arner, Urinary bladder contraction and relaxation: Physiology and pathophysiology. Physiol. Rev. 84, 935–986 (2004)

    Article  CAS  PubMed  Google Scholar 

  275. M.M. Barendrecht, M. Oelke, M.P. Laguna, et al., Is the use of parasympathomimetics for treating an underactive urinary bladder evidence-based? BJU Int. 99, 749 (2007)

    Article  CAS  PubMed  Google Scholar 

  276. A. Alhasso, C.M.A. Glazener, R. Pickard, et al., Adrenergic drugs for urinary incontinence in adults (review). Cochrane Database Syst. Rev. 3, CD001842 (2005)

    Google Scholar 

  277. A. Sharma, M.J. Goldberg, B.J. Cerimele, Pharmacokinetics and safety of duloxetine, a dual- serotonin and norepinephrine reuptake inhibitor. J. Clin. Pharmacol. 40, 161 (2000)

    Article  CAS  PubMed  Google Scholar 

  278. K.B. Thor, M. Kirby, L. Viktrup, Serotonin and noradrenaline involvement in urinary incontinence, depression and pain: Scientific basis for overlapping clinical efficacy from a single drug, duloxetine. Int. J. Clin. Pract. 61, 1349–1355 (2007)

    Article  CAS  PubMed  Google Scholar 

  279. D.J. Hurley, C.L. Turner, I. Yalcin, et al., Duloxetine for the treatment of stress urinary incontinence in women: An integrated analysis of safety. Eur. J. Obstet. Gynecol. Reprod. Biol. 125, 120–128 (2006)

    Article  CAS  PubMed  Google Scholar 

  280. M. Vella, J. Duckett, M. Basu, Duloxetine 1 year on: The long term outcome of a cohort of women prescribed duloxetine. Int. Urogynecol. J. Pelvic Floor Dysfunct. 19, 961–964 (2008)

    Article  PubMed  Google Scholar 

  281. R.C. Bump, S. Voss, A. Beardsworth, et al., Long-term efficacy of duloxetine in women with stress urinary incontinence. BJU Int. 102, 214–218 (2008)

    Article  CAS  PubMed  Google Scholar 

  282. K. Kaneko, S. Fujinaga, Y. Ohtomo, et al., Combined pharmacotherapy for nocturnal enuresis. Pediatr. Nephrol. 16, 662–664 (2001)

    Article  CAS  PubMed  Google Scholar 

  283. R. Natalin, L.O. Reis, C. Alpendre, et al., Triple therapy in refractory detrusor overactivity: A preliminary study. World J. Urol. 28, 79–85 (2010)

    Article  PubMed  Google Scholar 

  284. P. Abrams, C. Kelleher, D. Staskin, et al., Combination treatment with mirabegron and solifenacin in patients with overactive bladder: Exploratory responder analyses of efficacy and evaluation of patient-reported outcomes from a randomized, double-blind, factorial, dose-ranging, phase II study (SYMPHONY). World J. Urol. 35, 827–838 (2017)

    Article  CAS  PubMed  Google Scholar 

  285. O. Yamaguchi, H. Kakizaki, Y. Homma, et al., Safety and efficacy of mirabegron as ‘add-on’ therapy in patients with overactive bladder treated with solifenacin: A post-marketing, open-label study in Japan (MILAI study). BJU Int. 116, 612–622 (2015)

    Article  CAS  PubMed  Google Scholar 

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Andersson, KE., Madersbacher, H., Altaweel, W., Vasudeva, P., Igawa, Y. (2023). Drug Treatment. In: Liao, L., Madersbacher, H. (eds) Handbook of Neurourology. Springer, Singapore. https://doi.org/10.1007/978-981-99-1659-7_27

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