title: Discovery history and clinical development of mirabegron for the treatment of overactive bladder and urinary incontinence.
abstract: BACKGROUND
  Overactive bladder (OAB) and urinary incontinence, although not life-threatening, are very bothersome chronic health conditions. The limitations of current pharmacological treatment urge the need for novel drugs with alternative mechanisms of action. Huge efforts in this area of research led to the synthesis of several selective and potent β3-adrenoceptor agonists that gained relevance through research during the late 80s and 90s. Mirabegron was the first compound of this new class of drugs that showed preclinical efficacy in several models of storage bladder dysfunction, together with a favorable human pharmacological profile. Having passed the proof-of-concept stage, an extensive clinical development and pharmacology program was performed during the last 10 years, involving >10,000 individuals, before mirabegron was granted marketing approval.
  
  
  METHODS
  In this case history, the authors review the milestones in mirabegron's discovery based on a systematic literature review.
  
  
  CONCLUSIONS
  Thanks to its tolerability and safety/efficacy balance, mirabegron has potential to fill a need for new treatment options for OAB, and paves the way for further development of a completely new class of drugs aimed to treat this condition. However, the exact role of mirabegron in clinical practice has yet to be defined. Further studies are needed in order to clarify, together with post-launch information, critical safety issues and cost-effectiveness in head-to-head comparison with current standard treatments.
authors.affiliation: Catholic University Medical School of Rome, "Agostino Gemelli" Hospital, Urologic Clinic , Roma, 00168 , Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Sacco
authors.forename: Riccardo
authors.initials: R
authors.lastname: Bientinesi
authors.forename: Daniele
authors.initials: D
authors.lastname: Tienforti
authors.forename: Marco
authors.initials: M
authors.lastname: Racioppi
authors.forename: Gaetano
authors.initials: G
authors.lastname: Gulino
authors.forename: Daniele
authors.initials: D
authors.lastname: D'Agostino
authors.forename: Matteo
authors.initials: M
authors.lastname: Vittori
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Bassi
mesh_terms: D000083:Acetanilides / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D058667:Adrenergic beta-3 Receptor Agonists / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D006801:Humans; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D013844:Thiazoles / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*; D014549:Urinary Incontinence / Q000188:drug therapy*; D014551:Urinary Tract / Q000378:metabolism; D064804:Urological Agents / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000083:Acetanilides; D058667:Adrenergic beta-3 Receptor Agonists; D022702:Receptors, Adrenergic, beta-3; D013844:Thiazoles; D064804:Urological Agents; C520025:mirabegron