title: Pharmacological methods for the preclinical assessment of therapeutics for OAB: an up-to-date review.
abstract: BACKGROUND
  Licenced oral pharmacotherapies for overactive bladder (OAB) act on muscarinic receptors or β3-adrenoceptors. The search for new drugs to treat OAB that have novel mechanisms of action is very active, with the aim of discovering more effective and/or better tolerated agents.
  
  
  METHODS
  A literature review of the most frequently used pharmacological methods for the preclinical assessment of new agents aimed at treating OAB, such as isolated organ technique, electrophysiological techniques, radioligand binding assay, and animal models, was carried out. Novel potential developments based on recent knowledge of urothelial and neural mechanisms are also discussed.
  
  
  RESULTS
  The isolated organ technique, electrophysiological techniques, and the radioligand binding assay are very effective methods for the demonstration that a novel pharmacological target with a specific and high affinity binding site for a new drug is present in the bladder and its modulation regulates functions critical for the pathophysiology of OAB. Afterward, the new drug should be shown to be effective in animal models of OAB, although the translational value of these models is limited by a poor pathophysiological relationship with human OAB. Exciting novel perspectives focusing in particular on the theory of the mucosal-bladder network have recently opened new paths in the discovery and assessment of new therapeutics in this field.
  
  
  CONCLUSIONS
  Available experimental models still play a central role in the appraisal of OAB therapeutics; however, their shortcomings and the paucity of very effective drugs indicate the need for new models that better reproduce the pathophysiological features of OAB. Some emerging lines of research show promise. A change of perspective in the future evaluation of putative drugs is required, especially in the light of the latest knowledge on the key role of the mucosal-bladder network and the brain-bladder neural pathways.
authors.affiliation: Department of Urology, "Agostino Gemelli" Hospital, Catholic University Medical School, Rome, Italy. emilio.sacco@gmail.com.
authors.forename: Emilio
authors.initials: E
authors.lastname: Sacco
authors.affiliation: Department of Urology, "Agostino Gemelli" Hospital, Catholic University Medical School, Rome, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Bientinesi
authors.affiliation: Department of Urology, "Agostino Gemelli" Hospital, Catholic University Medical School, Rome, Italy.
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Bassi
authors.affiliation: Institute of Pharmacology, Catholic University Medical School, Largo Vito 1, 00168, Rome, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Currò
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical; D004599:Electric Stimulation Therapy; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D051379:Mice; D023421:Models, Animal; D018727:Muscarinic Antagonists / Q000493:pharmacokinetics; D018408:Patch-Clamp Techniques; D011817:Rabbits; D011869:Radioligand Assay / Q000379:methods; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects; D013552:Swine; D001743:Urinary Bladder / Q000187:drug effects*; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*
chemical_list: D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic
keywords: Animal models; Extracellular recordings; Isolated organ technique; Overactive bladder syndrome; Patch clamp; Radioligand binding assay