β3-Adrenoceptor Control of Lower Genitourinary Tract Organs and Function in Male: An Overview

Curr Drug Targets. 2018;19(6):602-612. doi: 10.2174/1389450118666170120165554.

Abstract

The sympathetic nervous system is one component of the nervous regulatory system of the physiological function of the lower genitourinary tract. Our knowledge on the role of this sympathetic system has advanced during the last decade due to the characterization of β3-adrenoceptors (β3-ARs) in the urogenital system. This review focuses on the pharmacological and molecular evidence supporting the functional roles of β3-AR in male genitourinary tissues of various species. An electronic search in two different databases was performed including MEDLINE (PubMed) and EMBASE from 2010 to 2016. β3-agonists may be a promising alternative to antimuscarinics in the treatment of overactive bladder (OAB) based on available evidence. Although more recent studies have evaluated the involvement of β3-ARs in the physiological control and regulation of various tissues of the lower genitourinary tract mainly urinary bladder, penis, urethra, ureter, there are few innovations in the pipe-line. Among the β3-agonists, mirabegron is a unique drug licensed for the treatment of patients with OAB. Many drugs classified as β3-agonists are still under investigations for the treatment of OAB, lower urinary tract symptoms, ureteral stones, benign prostate hyperplasia, prostate cancer and erectile dysfunction. This review discusses the potential roles of β3-AR as new therapeutic targets by evaluating the results of preclinical and clinical studies related to male lower genitourinary tract function. Looking into the future, the potential benefits of β3- AR agonists from experimental and clinical investigations may provide an attractive therapeutic option.

Keywords: drug effect; male urogenital system; mirabegron; overactive bladder; voiding; β3-adrenoceptor..

Publication types

  • Review

MeSH terms

  • Acetanilides / pharmacology
  • Acetanilides / therapeutic use
  • Adrenergic beta-3 Receptor Agonists / pharmacology
  • Adrenergic beta-3 Receptor Agonists / therapeutic use*
  • Animals
  • Humans
  • Lower Urinary Tract Symptoms / drug therapy
  • Lower Urinary Tract Symptoms / physiopathology
  • Male
  • Male Urogenital Diseases / drug therapy*
  • Male Urogenital Diseases / physiopathology
  • Muscarinic Antagonists / therapeutic use
  • Receptors, Adrenergic, beta-3 / drug effects*
  • Receptors, Adrenergic, beta-3 / metabolism
  • Thiazoles / pharmacology
  • Thiazoles / therapeutic use
  • Urinary Bladder, Overactive / drug therapy
  • Urinary Bladder, Overactive / physiopathology

Substances

  • Acetanilides
  • Adrenergic beta-3 Receptor Agonists
  • Muscarinic Antagonists
  • Receptors, Adrenergic, beta-3
  • Thiazoles
  • mirabegron