Investigational Drug Therapies for Overactive Bladder Syndrome: The Potential Alternatives to Anticolinergics

Background Overactive bladder is a high prevalent and quality of life affecting disease. The mainstay of the medical therapy is represented by antimuscarinic drugs, but their side effects markedly affect patient compliance and prompt studies on novel investigational drugs. Methods A systematic literature search of peer-reviewed papers and meeting abstracts published by December 2008 was performed. PubMed databank was searched for original English articles, by using the following search terms: “overactive bladder” or “detrusor overactivity” or “urinary incontinence” and “treatment”, alone and linked to any potential molecular target or novel drug cited in the literature. Results Effective alternative pharmacological treatments are currently scarce, but many new promising compounds are emerging which target key molecular pathways involved in micturition control. The most promising potential therapeutic targets include central nervous system GABAergic inhibitory pathway, dopaminergic and serotoninergic systems, b-adrenoceptors and cAMP metabolism, nonadrenergic-noncholinergic mechanisms such as purinergic and neuropeptidergic systems, vanilloid receptor, bladder sensory nervous terminals, nonneuronal bladder signalling systems including urothelium and interstitial cells, prostanoids, Rho-kinase and different subtypes of potassium and calcium channels. Conclusions Despite the enormous amount of new biologic insight, very few novel pharmacological therapies seems to have passed the proof-of-concept clinical stage. The ultimate clinical utility of new drugs will depend on the ability to exploit tissue-specific differences and disease-related changes in molecular expression/function and to improve storage phase dysfunctions without interfering with the emptying phase. Further preclinical investigations and controlled clinical trials are urgently needed in this challenging field.