Overactive bladder treatments in early phase clinical trials.
'Overactive bladder' (OAB) is a syndrome that is characterised by symptoms of urgency, with or without urge urinary incontinence, usually with frequency and nocturia [1] . It is a highly prevalent condition affecting 17% of the general population, with a significant negative effect on quality of life, impairing several areas with physical, social, emotional and sexual limitations. The prevalence of OAB increases with age in both men and women [2,3] . The pathophysiology is multifactorial and not yet fully understood. Non-surgical treatment is the mainstay of therapy for OAB. The available options include biofeedback, electrical stimulation, bladder training, pharmacotherapy or a combination of these options. Nevertheless pharmacotherapy is still the treatment of choice for OAB symptoms [4] . The pharmacological treatment of OAB is generally directed towards the central or the peripheral neural control pathways or the detrusor muscle [5] . The antimuscarinic drugs are the most commonly used. In the US, approved antimuscarinics include oxybutynin, tolterodine, trospium chloride, solifenacin and darifenacin. Although this class of drugs has been shown to be more effective than placebo in specific meta-analyses [6] , it has been reported that < or = 80% of the patients discontinue the treatment within 6 months, mainly for the low drug compliance due to the high incidence of side effects [7] . Therefore, there is a strong need to identify drugs with novel mechanisms of action, which could provide equal or even better efficacy and overall greater acceptability than antimuscarinic drugs. At present, several other specific molecular targets identified within detrusor muscle and/or neural systems are under investigation for the development of more specific treatments of OAB. This article provides an up-to date review of drugs that are in investigational preclinical and early stage (Phase I and II) clinical trials for the treatment of OAB.
Colli
Enrico
E
Bioxell SPA, Milan, Italy. enrico.colli@bioxell.com
Digesu
Giuseppe Alessandro
GA
Olivieri
Lorenza
L
D000818:Animals; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004195:Disease Models, Animal; D015507:Drugs, Investigational; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D018727:Muscarinic Antagonists / Q000627:therapeutic use*; D011812:Quinuclidines / Q000494:pharmacology / Q000627:therapeutic use*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D000069464:Solifenacin Succinate; D044005:Tetrahydroisoquinolines / Q000494:pharmacology / Q000627:therapeutic use*; D053201:Urinary Bladder, Overactive / Q000175:diagnosis / Q000188:drug therapy*
D015507:Drugs, Investigational; D006146:Guanidines; D018727:Muscarinic Antagonists; D011812:Quinuclidines; D011976:Receptors, Muscarinic; D044005:Tetrahydroisoquinolines; D000069464:Solifenacin Succinate; C004711:dicyandiamido