Emerging pharmacological targets in overactive bladder therapy: experimental and clinical evidences

Antimuscarinics are the mainstay of the medical therapy for overactive bladder, but their side effects and often modest success have prompted studies on novel pharmacological approaches. In this paper, we give a systematic literature review of peer-reviewed papers on the subject. Effective nonantimuscarinic 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: nervous GABAergic, glycinergic, dopaminergic, and serotonergic systems; b-adrenoceptors and cAMP metabolism; nonadrenergic-noncholinergic mechanisms such as purinergic and neuropeptidergic systems; vanilloid receptors; bladder afferent nerves; nonneuronal bladder signaling systems including urothelium and interstitial cells; prostanoids; Rho-kinase; and different subtypes of potassium and calcium channels. Despite the enormous amount of new biologic insight, very few drugs with mechanism of action other than antimuscarinics have passed as yet the proof-of-concept stage. Further preclinical and clinical studies are urgently needed in this rapidly moving field.