Innovative pharmacotherapies for women with overactive bladder: where are we now and what is in the pipeline?
OBJECTIVE
The impressive prevalence of overactive bladder (OAB) and the relevant limitations of current treatments urge the need for novel therapeutic approaches.


METHODS
A systematic literature and web search was performed to identify investigational drugs that entered the early and late phases of clinical development for women with OAB symptoms.


RESULTS
Approved pharmacological therapies for OAB (antimuscarinics, beta-3 agonists, and botulinum toxin) are evolving with the development of alternative administration methods, combination strategies, and novel compounds, expected to improve effectiveness, bladder selectivity, and dose flexibility. A wealth of investigational compounds, developed with both public and companies' indoor nonclinical disease-oriented studies, entered the early and late stages of clinical development in the last decade. Most non-anticholinergic compounds in ongoing clinical trials target central and peripheral neurotransmitter receptors involved in neurological modulation of micturition, nonadrenergic-noncholinergic mechanisms, cyclic nucleotide metabolism, different subtypes of ion channels or peripheral receptors of prostaglandins, vanilloids, vitamin D3, and opioids. Fascinating advances are ongoing also in the field of genetic therapy.


CONCLUSIONS
New pharmaceutical formulations and drug combinations are expected to be available in the next decade in order to overcome the limitations of current drugs for OAB. Although proof-of-concept, patient-oriented studies yielded disappointing results for several tentative drugs, a lot of clinical research is ongoing that is expected to provide clinicians with novel therapeutic agents in the near future.
Department of Urology, "Agostino Gemelli" Hospital, Catholic University Medical School, Rome, Italy, emilio.sacco@gmail.com.
Emilio
E
Sacco
Riccardo
R
Bientinesi
D058667:Adrenergic beta-3 Receptor Agonists / Q000627:therapeutic use; D019274:Botulinum Toxins, Type A / Q000627:therapeutic use; D015220:Calcium Channels / Q000187:drug effects; D055808:Drug Discovery; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D018727:Muscarinic Antagonists / Q000627:therapeutic use; D015221:Potassium Channels / Q000187:drug effects; D018167:Receptors, Calcitriol / Q000819:agonists; D011957:Receptors, Opioid / Q000819:agonists; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors / Q000627:therapeutic use; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*
D058667:Adrenergic beta-3 Receptor Agonists; D019274:Botulinum Toxins, Type A; D015220:Calcium Channels; D015507:Drugs, Investigational; D018727:Muscarinic Antagonists; D015221:Potassium Channels; D018167:Receptors, Calcitriol; D011957:Receptors, Opioid; D011982:Receptors, Prostaglandin; D018039:Receptors, Tachykinin; D017367:Selective Serotonin Reuptake Inhibitors; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human