Novel pharmacotherapeutic avenues for bladder storage dysfunction in men

References

• Sexton CC, Coyne KS, Kopp ZS, et al. The overlap of storage, voiding and postmicturition symptoms and implications for treatment seeking in the USA, UK and Sweden: EpiLUTS. BJU Int. 2009;103 Suppl 3(s3):12–23. doi: 10.1111/j.1464-410X.2009.08369.x
   PubMedGoogle Scholar
• Moon S, Kim YJ, Chung HS, et al. The relationship between nocturia and mortality: data from the national health and nutrition examination survey. Int Neurourol J. 2022;26(2):144–152. doi: 10.5213/inj.2142370.185
   PubMed Web of Science ®Google Scholar
• Welk B, McClure JA. The reduction of male lower urinary tract symptoms is associated with a decreased risk of death. J Urol. 2023;210(4):670–677. doi: 10.1097/JU.0000000000003602
   PubMed Web of Science ®Google Scholar
• Yeowell G, Smith P, Nazir J, et al. Real-world persistence and adherence to oral antimuscarinics and mirabegron in patients with overactive bladder (OAB): a systematic literature review. BMJ Open. 2018;8(11):e021889. doi: 10.1136/bmjopen-2018-021889
   PubMed Web of Science ®Google Scholar
• Kleinman NL, Odell K, Chen CI, et al. Persistence and adherence with urinary antispasmodic medications among employees and the impact of adherence on costs and absenteeism. J Manag Care Spec Pharm. 2014;20(10):1047–1056. doi: 10.18553/jmcp.2014.20.10.1047
   PubMedGoogle Scholar
• Kalder M, Pantazis K, Dinas K, et al. Discontinuation of treatment using anticholinergic medications in patients with urinary incontinence. Obstet Gynecol. 2014;124(4):794–800. doi: 10.1097/AOG.0000000000000468
   PubMed Web of Science ®Google Scholar
• Wada N, Watanabe M, Banjo H, et al. Long-term persistence with mirabegron in a real-world clinical setting. Int J Urol. 2018;25(5):501–506. doi: 10.1111/iju.13558
   PubMed Web of Science ®Google Scholar
• Chen Y, Peng L, Zhang C, et al. The effectiveness and safety of oral medications, onabotulinumtoxinA (three doses) and transcutaneous tibial nerve stimulation as non or minimally invasive treatment for the management of neurogenic detrusor overactivity in adults: a systematic review and network meta-analysis. Int J Surg. 2023;109(5):1430–1438. doi: 10.1097/JS9.0000000000000338
   PubMed Web of Science ®Google Scholar
• Yokoyama O, Honda M, Yamanishi T, et al. Efficacy and safety of onabotulinumtoxinA in patients with overactive bladder: subgroup analyses by sex and by serum prostate-specific antigen levels in men from a randomized controlled trial. Int Urol Nephrol. 2021;53(11):2243–2250. doi: 10.1007/s11255-021-02962-z
   PubMed Web of Science ®Google Scholar
• Apostolidis A. Combination treatments for overactive bladder refractory to first-line pharmacotherapy: do they meet expectations? BJU Int. 2017;120(4):459–460. doi: 10.1111/bju.13988
   PubMed Web of Science ®Google Scholar
• Pang R, Zhou XY, Wang X, et al. Anticholinergics combined with alpha-blockers for treating lower urinary tract symptoms related to benign prostatic obstruction. Cochrane Database Syst Rev. 2021;2(2):Cd012336. doi: 10.1002/14651858.CD012336.pub2
   PubMedGoogle Scholar
• de Groat WC, Griffiths D, Yoshimura N. Neural control of the lower urinary tract. Compr Physiol. 2015;5(1):327–396.
   PubMed Web of Science ®Google Scholar
• Peyronnet B, Mironska E, Chapple C, et al. A comprehensive review of overactive bladder pathophysiology: on the way to tailored treatment. Eur Urol. 2019;75(6):988–1000. doi: 10.1016/j.eururo.2019.02.038
   PubMed Web of Science ®Google Scholar
• Andersson KE. Storage and voiding symptoms: pathophysiologic aspects. Urology. 2003;62(5 Suppl 2):3–10. doi: 10.1016/j.urology.2003.09.030
   PubMedGoogle Scholar
• Funahashi Y, Takahashi R, Mizoguchi S, et al. Bladder overactivity and afferent hyperexcitability induced by prostate-to-bladder cross-sensitization in rats with prostatic inflammation. J Physiol. 2019;597(7):2063–2078. doi: 10.1113/JP277452
   PubMed Web of Science ®Google Scholar
• Ishihama H, Momota Y, Yanase H, et al. Activation of alpha1D adrenergic receptors in the rat urothelium facilitates the micturition reflex. J Urol. 2006;175(1):358–364. doi: 10.1016/S0022-5347(05)00016-9
   PubMed Web of Science ®Google Scholar
• Aizawa N, Sugiyama R, Ichihara K, et al. Functional roles of bladder α1-adrenoceptors in the activation of single-unit primary bladder afferent activity in rats. BJU Int. 2016;117(6):993–1001. doi: 10.1111/bju.13313
   PubMed Web of Science ®Google Scholar
• Yazaki J, Aikawa K, Shishido K, et al. Alpha1-adrenoceptor antagonists improve bladder storage function through reduction of afferent activity in rats with bladder outlet obstruction. Neurourol Urodyn. 2011;30(3):461–467. doi: 10.1002/nau.20984
   PubMed Web of Science ®Google Scholar
• Lee MJ, Moon JH, Lee HK, et al. Pharmacological characterization of DA-8010, a novel muscarinic receptor antagonist selective for urinary bladder over salivary gland. Eur J Pharmacol. 2019;843:240–250. doi: 10.1016/j.ejphar.2018.11.037
   PubMed Web of Science ®Google Scholar
• Son HS, Oh CY, Choo MS, et al. Efficacy and safety of DA-8010, a novel M3 antagonist, in patients with overactive bladder: a randomized, double-blind phase 2 study. Int Neurourol J. 2022;26(2):119–128. doi: 10.5213/inj.2142382.191
   PubMed Web of Science ®Google Scholar
• Brucker BM, King J, Mudd PN Jr., et al. Selectivity and maximum response of vibegron and mirabegron for β(3)-adrenergic receptors. Curr Ther Res Clin Exp. 2022;96:100674. doi: 10.1016/j.curtheres.2022.100674
   PubMed Web of Science ®Google Scholar
• Ohlstein EH, von Keitz A, Michel MC. A multicenter, double-blind, randomized, placebo-controlled trial of the β3-adrenoceptor agonist solabegron for overactive bladder. Eur Urol. 2012;62(5):834–840. doi: 10.1016/j.eururo.2012.05.053
   PubMed Web of Science ®Google Scholar
• Maruyama I, Yonekubo S, Tatemichi S, et al. Effects of ritobegron (KUC-7483), a novel β3-adrenoceptor agonist, on both rat bladder function following partial bladder outlet obstruction and on rat salivary secretion: a comparison with the effects of tolterodine. J Smooth Muscle Res. 2012;48(5–6):115–124. doi: 10.1540/jsmr.48.115
   PubMedGoogle Scholar
• Ishikawa K, Tsujimura A, Miyoshi M, et al. Efficacy and safety of vibegron add-on therapy in men with persistent storage symptoms after receiving alpha 1-blocker or phosphodiesterase 5 inhibitor: a preliminary study. Urology. 2021;153:256–263. doi: 10.1016/j.urology.2021.01.021
   PubMed Web of Science ®Google Scholar
• Burnstock G. Purinergic signalling in the urinary tract in health and disease. Purinergic Signal. 2014;10(1):103–155. doi: 10.1007/s11302-013-9395-y
   PubMed Web of Science ®Google Scholar
• Klein S, Gashaw I, Baumann S, et al. First-in-human study of eliapixant (BAY 1817080), a highly selective P2X3 receptor antagonist: tolerability, safety and pharmacokinetics. Br J Clin Pharmacol. 2022;88(10):4552–4564. doi: 10.1111/bcp.15358
   PubMed Web of Science ®Google Scholar
• Kum E, Patel M, Diab N, et al. Efficacy and tolerability of gefapixant for treatment of refractory or unexplained chronic cough: a systematic review and Dose-Response Meta-Analysis. JAMA. 2023;330(14):1359–1369. doi: 10.1001/jama.2023.18035
   PubMed Web of Science ®Google Scholar
• Kim JC, Kim DB, Seo SI, et al. Nerve growth factor and vanilloid receptor expression, and detrusor instability, after relieving bladder outlet obstruction in rats. BJU Int. 2004;94(6):915–918. doi: 10.1111/j.1464-4096.2003.05059.x
   PubMed Web of Science ®Google Scholar
• Santos-Silva A, Charrua A, Cruz CD, et al. Rat detrusor overactivity induced by chronic spinalization can be abolished by a transient receptor potential vanilloid 1 (TRPV1) antagonist. Auton Neurosci. 2012;166(1–2):35–38. doi: 10.1016/j.autneu.2011.09.005
   PubMed Web of Science ®Google Scholar
• Park CW, Kim BJ, Lee YW, et al. Asivatrep, a TRPV1 antagonist, for the topical treatment of atopic dermatitis: phase 3, randomized, vehicle-controlled study (CAPTAIN-AD). J Allergy Clin Immunol. 2022;149(4):1340–1347.e1344. doi: 10.1016/j.jaci.2021.09.024
   PubMed Web of Science ®Google Scholar
• Mayorga AJ, Flores CM, Trudeau JJ, et al. A randomized study to evaluate the analgesic efficacy of a single dose of the TRPV1 antagonist mavatrep in patients with osteoarthritis. Scand J Pain. 2017;17(1):134–143. doi: 10.1016/j.sjpain.2017.07.021
   PubMedGoogle Scholar
• Wu Y, Qi J, Wu C, et al. Emerging roles of the TRPV4 channel in bladder physiology and dysfunction. J Physiol. 2021;599(1):39–47. doi: 10.1113/JP279776
   PubMed Web of Science ®Google Scholar
• Goyal N, Skrdla P, Schroyer R, et al. Clinical pharmacokinetics, safety, and tolerability of a novel, first-in-class TRPV4 ion channel inhibitor, GSK2798745, in healthy and heart failure subjects. Am J Cardiovasc Drugs. 2019;19(3):335–342. doi: 10.1007/s40256-018-00320-6
   PubMed Web of Science ®Google Scholar
• Streng T, Axelsson HE, Hedlund P, et al. Distribution and function of the hydrogen sulfide-sensitive TRPA1 ion channel in rat urinary bladder. Eur Urol. 2008;53(2):391–399. doi: 10.1016/j.eururo.2007.10.024
   PubMed Web of Science ®Google Scholar
• DeBerry JJ, Schwartz ES, Davis BM. TRPA1 mediates bladder hyperalgesia in a mouse model of cystitis. Pain. 2014;155(7):1280–1287. doi: 10.1016/j.pain.2014.03.023
   PubMed Web of Science ®Google Scholar
• Lashinger ES, Steiginga MS, Hieble JP, et al. AMTB, a TRPM8 channel blocker: evidence in rats for activity in overactive bladder and painful bladder syndrome. Am J Physiol Renal Physiol. 2008;295(3):F803–810. doi: 10.1152/ajprenal.90269.2008
   PubMed Web of Science ®Google Scholar
• Aizawa N, Fujimori Y, Kobayashi JI, et al. KPR-2579, a novel TRPM8 antagonist, inhibits acetic acid-induced bladder afferent hyperactivity in rats. Neurourol Urodyn. 2018;37(5):1633–1640. doi: 10.1002/nau.23532
   PubMed Web of Science ®Google Scholar
• Wada N, Shimizu T, Shimizu N, et al. The effect of neutralization of nerve growth factor (NGF) on bladder and urethral dysfunction in mice with spinal cord injury. Neurourol Urodyn. 2018;37(6):1889–1896. doi: 10.1002/nau.23539
   PubMed Web of Science ®Google Scholar
• Patel MK, Kaye AD, Urman RD. Tanezumab: therapy targeting nerve growth factor in pain pathogenesis. J Anaesthesiol Clin Pharmacol. 2018;34(1):111–116. doi: 10.4103/joacp.JOACP_389_15
   PubMed Web of Science ®Google Scholar
• Liu Q, Li X, Zhu J, et al. TrkA inhibition alleviates bladder overactivity in cyclophosphamide-induced cystitis by targeting hyperpolarization-activated cyclic nucleotide-gated channels. Iran J Basic Med Sci. 2023;26(6):701–707. doi: 10.22038/IJBMS.2023.68528.14943
   PubMed Web of Science ®Google Scholar
• Suzuki T, Shimizu T, Karnup S, et al. Therapeutic effects of p38 mitogen-activated protein kinase inhibition on hyperexcitability of capsaicin sensitive bladder afferent neurons in mice with spinal cord injury. Life Sci. 2023;325:121738. doi: 10.1016/j.lfs.2023.121738
   PubMed Web of Science ®Google Scholar
• Mossa AH, Galan A, Cammisotto PG, et al. Antagonism of proNGF or its receptor p75(NTR) reverses remodelling and improves bladder function in a mouse model of diabetic voiding dysfunction. Diabetologia. 2020;63(9):1932–1946. doi: 10.1007/s00125-020-05222-4
   PubMed Web of Science ®Google Scholar
• Kim SJ, Park EY, Hwang TK, et al. Therapeutic effects of connexin inhibitors on detrusor overactivity induced by bladder outlet obstruction in rats. Urology. 2011;78(2):475.e471–477. doi: 10.1016/j.urology.2011.03.029
   Web of Science ®Google Scholar
• Babaoglu M, Zumrutbas AE, Acar IC, et al. Gap junction expression and the effects of gap junction inhibitors in overactive bladder models: does ovariectomy have a role? Int Urol Nephrol. 2013;45(4):1001–1008. doi: 10.1007/s11255-013-0488-x
   PubMed Web of Science ®Google Scholar
• Walczak JS, Cervero F. Local activation of cannabinoid CB(1) receptors in the urinary bladder reduces the inflammation-induced sensitization of bladder afferents. Mol Pain. 2011;7:31. doi: 10.1186/1744-8069-7-31
   PubMed Web of Science ®Google Scholar
• Wang ZY, Wang P, Bjorling DE. Activation of cannabinoid receptor 1 inhibits increased bladder activity induced by nerve growth factor. Neurosci Lett. 2015;589:19–24. doi: 10.1016/j.neulet.2015.01.009
   PubMed Web of Science ®Google Scholar
• Christie S, Zagorodnyuk V. CB2 cannabinoid receptor agonist selectively inhibits the mechanosensitivity of mucosal afferents in the guinea pig bladder. Am J Physiol Renal Physiol. 2021;320(5):F859–f865. doi: 10.1152/ajprenal.00065.2021
   PubMed Web of Science ®Google Scholar
• Liu Q, Wu Z, Liu Y, et al. Cannabinoid receptor 2 activation decreases severity of cyclophosphamide-induced cystitis via regulating autophagy. Neurourol Urodyn. 2020;39(1):158–169. doi: 10.1002/nau.24205
   PubMed Web of Science ®Google Scholar
• Strittmatter F, Gandaglia G, Benigni F, 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. 2012;61(1):98–106. doi: 10.1016/j.eururo.2011.09.002
   PubMed Web of Science ®Google Scholar
• Charrua A, Matos R, Oliveira R, et al. Fatty acid amide hydrolase inhibition normalises bladder function and reduces pain through normalising the anandamide/palmitoylethanolamine ratio in the inflamed bladder of rats. Naunyn Schmiedebergs Arch Pharmacol. 2020;393(2):263–272. doi: 10.1007/s00210-019-01729-9
   PubMed Web of Science ®Google Scholar
• Wagenlehner FME, van Till JWO, Houbiers JGA, et al. Fatty acid amide hydrolase inhibitor treatment in men with chronic prostatitis/chronic pelvic pain syndrome: an adaptive double-blind, randomized controlled trial. Urology. 2017;103:191–197. doi: 10.1016/j.urology.2017.02.029
   PubMed Web of Science ®Google Scholar
• Gil-Ordóñez A, Martín-Fontecha M, Ortega-Gutiérrez S, et al. Monoacylglycerol lipase (MAGL) as a promising therapeutic target. Biochem Pharmacol. 2018;157:18–32. doi: 10.1016/j.bcp.2018.07.036
   PubMed Web of Science ®Google Scholar
• Chinnadurai A, Berger G, Burkovskiy I, et al. Monoacylglycerol lipase inhibition as potential treatment for interstitial cystitis. Med Hypotheses. 2019;131:109321. doi: 10.1016/j.mehy.2019.109321
   PubMed Web of Science ®Google Scholar
• Tsai TC, Lin CH, Chung HH, et al. Urinary bladder relaxation through activation of imidazoline receptors induced by agmatine is increased in diabetic rats. Low Urin Tract Symptoms. 2014;6(2):117–123. doi: 10.1111/luts.12031
   PubMed Web of Science ®Google Scholar
• Zhou F, Li H, Zhou C, et al. Structural and functional changes in gap junctional intercellular communication in a rat model of overactive bladder syndrome induced by partial bladder outlet obstruction. Exp Ther Med. 2016;11(6):2139–2146. doi: 10.3892/etm.2016.3246
   PubMed Web of Science ®Google Scholar
• Fry CH, Chakrabarty B, Hashitani H, et al. New targets for overactive bladder-ICI-RS 2109. Neurourol Urodyn. 2020;39 Suppl 3(Suppl 3):S113–s121. doi: 10.1002/nau.24228
   PubMedGoogle Scholar
• Matos R, Cordeiro JM, Coelho A, et al. Bladder pain induced by prolonged peripheral alpha 1A adrenoceptor stimulation involves the enhancement of transient receptor potential vanilloid 1 activity and an increase of urothelial adenosine triphosphate release. Acta Physiol (Oxf). 2016;218(4):265–275. doi: 10.1111/apha.12744
   PubMed Web of Science ®Google Scholar
• Hattori T, Sugaya K. Mechanisms of action for α(1)-adrenoceptor blockers in storage symptoms with new insights into the micturition reflex. Life Sci. 2017;191:90–96.
   PubMed Web of Science ®Google Scholar
• Lee JY, Park JM, Na YG, et al. Expression of bladder α(1)-adrenoceptor subtype after relief of partial bladder outlet obstruction in a rat model. Investig Clin Urol. 2020;61(3):297–303. doi: 10.4111/icu.2020.61.3.297
   PubMed Web of Science ®Google Scholar
• Johnson TM 2nd, Goode PS, Hammontree L, et al. An exploratory analysis of tamsulosin for overactive bladder (OAB) in men with varying voiding symptom burden. Urology. 2021;153:42–48. doi: 10.1016/j.urology.2021.01.022
   PubMed Web of Science ®Google Scholar
• Cho S, Kwon SS, Lee KW, et al. A multicenter real-life study of the efficacy of an alpha-blocker with or without anticholinergic agent (imidafenacin) treatment in patients with lower urinary tract symptoms/benign prostatic hyperplasia and storage symptoms. Int J Clin Pract. 2017;71(5):e12938. doi: 10.1111/ijcp.12938
   Web of Science ®Google Scholar
• Su YT, Chen HL, Teoh JY, et al. Comparison of add-on medications for persistent storage symptoms after α-blocker treatment in BPH patients - a network meta-analysis. BMC Urol. 2023;23(1):154. doi: 10.1186/s12894-023-01327-1
   PubMed Web of Science ®Google Scholar
• Drake MJ, Chapple C, Sokol R, et al. Long-term safety and efficacy of single-tablet combinations of solifenacin and tamsulosin oral controlled absorption system in men with storage and voiding lower urinary tract symptoms: results from the NEPTUNE study and NEPTUNE II open-label extension. Eur Urol. 2015;67(2):262–270. doi: 10.1016/j.eururo.2014.07.013
   PubMed Web of Science ®Google Scholar
• Rees J, Foley S, Huang M, et al. Vesomni improves the quality of life in men with lower urinary tract symptoms in routine clinical practice in Europe. Neurourol Urodyn. 2019;38(3):981–989. doi: 10.1002/nau.23944
   PubMed Web of Science ®Google Scholar
• Landeira M, Mora Blázquez AM, Martins de Almeida R, et al. A retrospective analysis comparing persistence and adherence to treatment with free- vs fixed-dose combination of an alpha blocker and an antimuscarinic agent in men with LUTS in Spain. Int J Clin Pract. 2020;74(11):e13616. doi: 10.1111/ijcp.13616
   PubMed Web of Science ®Google Scholar
• Chapple CR, Mironska E, Wagg A, et al. Multicriteria decision analysis applied to the clinical use of pharmacotherapy for overactive bladder symptom complex. Eur Urol Focus. 2020;6(3):522–530. doi: 10.1016/j.euf.2019.09.020
   PubMedGoogle Scholar
• Araklitis G, Robinson D. The cognitive safety of antimuscarinics in the treatment of overactive bladder. Expert Opin Drug Saf. 2020;19(10):1303–1313. doi: 10.1080/14740338.2020.1817377
   PubMed Web of Science ®Google Scholar
• Shin W, Yang AY, Yoo H, et al. Drug–drug interactions between tamsulosin and mirabegron in healthy individuals do not affect pharmacokinetics and hemodynamic parameters significantly. Pharmaceuticals (Basel). 2023;16(10):1457. doi: 10.3390/ph16101457
   PubMedGoogle Scholar
• Kakizaki H, Lee KS, Yamamoto O, et al. 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. 2020;6(4):729–737. doi: 10.1016/j.euf.2019.10.019
   PubMedGoogle Scholar
• Wu Y, Li G, Zhou H, et al. Mirabegron add-on tamsulosin for men with overactive bladder symptoms: a pooled analysis of four randomized controlled trials. Urol Int. 2024;108(2):118–127. doi: 10.1159/000536110
   PubMed Web of Science ®Google Scholar
• Kang TW, Kim SJ, Kim MH, et al. Beta 3 adrenoreceptor agonist for the management of lower urinary tract symptoms in men with benign prostatic hyperplasia: a systematic review. Int Neurourol J. 2021;25(3):182–191. doi: 10.5213/inj.2142068.034
   PubMed Web of Science ®Google Scholar
• Lee WC, Leu S, Wu KLH, et al. Tadalafil ameliorates bladder overactivity by restoring insulin-activated detrusor relaxation via the bladder mucosal IRS/PI3K/AKT/eNOS pathway in fructose-fed rats. Sci Rep. 2021;11(1):8202. doi: 10.1038/s41598-021-87505-3
   PubMed Web of Science ®Google Scholar
• Yamanishi T, Kaga K, Sakata K, et al. A randomized controlled study of the efficacy of tadalafil monotherapy versus combination of tadalafil and mirabegron for the treatment of persistent overactive bladder symptoms in men presenting with lower urinary tract symptoms (CONTACT study). Neurourol Urodyn. 2020;39(2):804–812. doi: 10.1002/nau.24285
   PubMed Web of Science ®Google Scholar
• Honda M, Kimura Y, Teraoka S, et al. Efficacy of combination treatment with tadalafil and mirabegron in patients with benign prostatic hyperplasia who presented with persistent storage symptoms after Tadalafil Monotreatment: a prospective, multicenter, open-labeled study. Yonago Acta Med. 2022;65(3):231–237. doi: 10.33160/yam.2022.08.009
   PubMed Web of Science ®Google Scholar
• Maruyama I, Yamamoto S, Tsuchioka K, et al. Effects of vibegron, a novel β(3)-adrenoceptor agonist, and its combination with imidafenacin or silodosin in a rat with partial bladder outlet obstruction. Eur J Pharmacol. 2020;878:173096. doi: 10.1016/j.ejphar.2020.173096
   PubMed Web of Science ®Google Scholar
• Shin JH, Jeong SJ, Kim SO, et al. A randomized, double-blind, placebo-controlled, bridging study to evaluate the efficacy and safety of vibegron in treating Korean patients with overactive bladder. Int Neurourol J. 2023;27(2):106–115. doi: 10.5213/inj.2346022.011
   PubMed Web of Science ®Google Scholar
• Dmochowski RR, Rovner ES, Kennelly MJ, et al. Study design of a phase 4, real-world study (COMPOSUR) to evaluate vibegron in patients with overactive bladder. BMC Urol. 2023;23(1):64. doi: 10.1186/s12894-023-01240-7
   PubMed Web of Science ®Google Scholar
• Song M, Kim JH, Lee KS, et al. The efficacy and tolerability of tarafenacin, a new muscarinic acetylcholine receptor M3 antagonist in patients with overactive bladder; randomised, double-blind, placebo-controlled phase 2 study. Int J Clin Pract. 2015;69(2):242–250. doi: 10.1111/ijcp.12540
   PubMed Web of Science ®Google Scholar
• Zacche MM, Giarenis I, Cardozo L. Phase II drugs that target cholinergic receptors for the treatment of overactive bladder. Expert Opin Investig Drugs. 2014;23(10):1365–1374. doi: 10.1517/13543784.2014.925877
   PubMed Web of Science ®Google Scholar
• Nureki I, Kobayashi K, Tanaka T, et al. Cryo-EM structures of the β(3) adrenergic receptor bound to solabegron and isoproterenol. Biochem Biophys Res Commun. 2022;611:158–164. doi: 10.1016/j.bbrc.2022.04.065
   PubMed Web of Science ®Google Scholar
• Abe Y, Nakano Y, Kanazawa T, et al. Investigation of drug-drug interactions between ritobegron, a selective β3 -adrenoceptor agonist, with probenecid in healthy men. Clin Pharmacol Drug Dev. 2016;5(3):201–207. doi: 10.1002/cpdd.212
   PubMed Web of Science ®Google Scholar
• Kim JC, Yoo JS, Park EY, et al. Muscarinic and purinergic receptor expression in the urothelium of rats with detrusor overactivity induced by bladder outlet obstruction. BJU Int. 2008;101(3):371–375. doi: 10.1111/j.1464-410X.2007.07251.x
   PubMed Web of Science ®Google Scholar
• Ferguson AC, Sutton BW, Boone TB, et al. Inhibition of urothelial P2X3 receptors prevents desensitization of purinergic detrusor contractions in the rat bladder. BJU Int. 2015;116(2):293–301. doi: 10.1111/bju.13003
   PubMed Web of Science ®Google Scholar
• Takezawa K, Kondo M, Kiuchi H, et al. Authentic role of ATP signaling in micturition reflex. Sci Rep. 2016;6(1):19585. doi: 10.1038/srep19585
   PubMedGoogle Scholar
• Morice A, Smith JA, McGarvey L, et al. Eliapixant (BAY 1817080), a P2X3 receptor antagonist, in refractory chronic cough: a randomised, placebo-controlled, crossover phase 2a study. Eur Respir J. 2021;58(5):2004240. doi: 10.1183/13993003.04240-2020
   PubMed Web of Science ®Google Scholar
• Ewerton F, Cruz F, Kapp M, et al. Efficacy and safety of eliapixant in overactive bladder: the 12-week, randomised, placebo-controlled phase 2a OVADER study. Eur Urol Focus. 2024;10(1):90–97. doi: 10.1016/j.euf.2023.07.008
   PubMedGoogle Scholar
• Moldwin R, Kitt M, Mangel J, et al. A phase 2 study in women with interstitial cystitis/bladder pain syndrome (IC/BPS) of the novel P2X3 antagonist AF-219. Neurourol Urodyn. 2015;34:S77–78.
   Web of Science ®Google Scholar
• Dicpinigaitis P, Birring SS, Cardozo L, et al. Patient-reported cough severity in women with chronic cough and stress urinary incontinence treated with gefapixant. Eur Respir J. 2023;62(suppl 67):A3039.
   Google Scholar
• Ramsey IS, Delling M, Clapham DE. An introduction to TRP channels. Annu Rev Physiol. 2006;68(1):619–647. doi: 10.1146/annurev.physiol.68.040204.100431
   PubMed Web of Science ®Google Scholar
• Daly D, Rong W, Chess-Williams R, et al. Bladder afferent sensitivity in wild-type and TRPV1 knockout mice. J Physiol. 2007;583(Pt 2):663–674. doi: 10.1113/jphysiol.2007.139147
   PubMed Web of Science ®Google Scholar
• Skryma R, Prevarskaya N, Gkika D, et al. From urgency to frequency: facts and controversies of TRPs in the lower urinary tract. Nat Rev Urol. 2011;8(11):617–630. doi: 10.1038/nrurol.2011.142
   PubMed Web of Science ®Google Scholar
• Ramsay S, Keightley L, Brookes S, et al. TRPV1 and TRPM8 antagonists reduce cystitis-induced bladder hypersensitivity via inhibition of different sensitised classes of bladder afferents in guinea pigs. Br J Pharmacol. 2023;180(11):1482–1499. doi: 10.1111/bph.16017
   PubMed Web of Science ®Google Scholar
• Charrua A, Cruz CD, Narayanan S, et al. GRC-6211, a new oral specific TRPV1 antagonist, decreases bladder overactivity and noxious bladder input in cystitis animal models. J Urol. 2009;181(1):379–386. doi: 10.1016/j.juro.2008.08.121
   PubMed Web of Science ®Google Scholar
• Cho KJ, Park EY, Kim HS, et al. Expression of transient receptor potential vanilloid 4 and effects of ruthenium red on detrusor overactivity associated with bladder outlet obstruction in rats. World J Urol. 2014;32(3):677–682. doi: 10.1007/s00345-013-1099-y
   PubMed Web of Science ®Google Scholar
• Cho KJ, Koh JS, Choi JB, et al. Changes in transient receptor potential vanilloid 1 and transient receptor potential vanilloid 4 in patients with lower urinary tract dysfunction. Investig Clin Urol. 2022;63(3):309–315. doi: 10.4111/icu.20210418
   PubMed Web of Science ®Google Scholar
• Ludbrook VJ, Hanrott KE, Kreindler JL, et al. Adaptive study design to assess effect of TRPV4 inhibition in patients with chronic cough. ERJ Open Res. 2021;7(3):00269–2021. doi: 10.1183/23120541.00269-2021
   PubMedGoogle Scholar
• Christie S, Brookes S, Zagorodnyuk V. Endocannabinoids in bladder sensory mechanisms in health and diseases. Front Pharmacol. 2021;12:708989.
   PubMed Web of Science ®Google Scholar
• Kim SD, Cho KJ, Kim JC. Expression of cannabinoid 1 and, 2 receptors and the effects of cannabinoid 1 and, 2 receptor agonists on detrusor overactivity associated with bladder outlet obstruction in rats. BMC Urol. 2017;17(1):121. doi: 10.1186/s12894-017-0313-4
   PubMedGoogle Scholar
• Füllhase C, Campeau L, Sibaev A, et al. Bladder function in a cannabinoid receptor type 1 knockout mouse. BJU Int. 2014;113(1):144–151. doi: 10.1111/bju.12350
   PubMed Web of Science ®Google Scholar
• Campeau L, Füllhase C, Sawada N, et al. Characterization of bladder function in a cannabinoid receptor type 2 knockout mouse in vivo and in vitro. Neurourol Urodyn. 2014;33(5):566–570. doi: 10.1002/nau.22454
   PubMed Web of Science ®Google Scholar
• Zapala L, Niemczyk G, Zapala P, et al. The cannabinoid ligand arachidonyl-2’-chloroethylamide (ACEA) ameliorates depressive and overactive bladder symptoms in a corticosterone-induced female wistar rat model. Int J Mol Sci. 2023;24(4):3820. doi: 10.3390/ijms24043820
   PubMed Web of Science ®Google Scholar
• Wrobel A, Szopa A, Serefko A, et al. A novel alternative in the treatment of detrusor overactivity? In vivo activity of O-1602, the newly synthesized agonist of GPR55 and GPR18 cannabinoid receptors. Molecules. 2020;25(6):1384. doi: 10.3390/molecules25061384
   PubMed Web of Science ®Google Scholar
• Füllhase C, Russo A, Castiglione F, et al. Spinal cord FAAH in normal micturition control and bladder overactivity in awake rats. J Urol. 2013;189(6):2364–2370. doi: 10.1016/j.juro.2012.11.165
   PubMed Web of Science ®Google Scholar
• Houbiers JGA, van Till JWO, Kaper M, et al. An adaptive randomized clinical trial in interstitial cystitis/bladder pain syndrome evaluating efficacy of ASP3652 and the relationship between disease characteristics and hunner’s lesions. World J Urol. 2021;39(6):2065–2071. doi: 10.1007/s00345-020-03372-z
   PubMed Web of Science ®Google Scholar
• Mulvihill MM, Nomura DK. Therapeutic potential of monoacylglycerol lipase inhibitors. Life Sci. 2013;92(8–9):492–497. doi: 10.1016/j.lfs.2012.10.025
   PubMed Web of Science ®Google Scholar
• Zhao YR, Liu WZ, Guralnick M, et al. Predictors of short-term overactive bladder symptom improvement after transurethral resection of prostate in men with benign prostatic obstruction. Int J Urol. 2014;21(10):1035–1040. doi: 10.1111/iju.12482
   PubMed Web of Science ®Google Scholar
• Wang J, Yang B, Zhang W, et al. The relationship between bladder storage function and frequent micturition after TURP. World J Urol. 2022;40(8):2055–2062. doi: 10.1007/s00345-022-04079-z
   PubMed Web of Science ®Google Scholar
• Yu SH, Jung SI. The potential role of urinary microbiome in benign prostate hyperplasia/lower urinary tract symptoms. Diagn (Basel). 2022;12(8):1862. doi: 10.3390/diagnostics12081862
   PubMedGoogle Scholar
• Hartigan SM, Dmochowski RR. Gender specific pharmacokinetic and pharmacodynamic considerations for antimuscarinic drugs for overactive bladder treatment. Expert Opin Drug Metab Toxicol. 2020;16(2):103–110. doi: 10.1080/17425255.2020.1714591
   PubMed Web of Science ®Google Scholar