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Muscarinic receptors: their distribution and function in body systems, and the implications for treating overactive bladder

Abrams, P ; Andersson, Karl-Erik LU orcid ; Buccafusco, JJ ; Chapple, C ; de Groat, WC ; Fryer, AD ; Kay, G ; Laties, A ; Nathanson, NM and Pasricha, PJ , et al. (2006) In British Journal of Pharmacology 148(5). p.565-578
Abstract
1 The effectiveness of antimuscarinic agents in the treatment of the overactive bladder (OAB) syndrome is thought to arise through blockade of bladder muscarinic receptors located on detrusor smooth muscle cells, as well as on nondetrusor structures. 2 Muscarinic M-3 receptors are primarily responsible for detrusor contraction. Limited evidence exists to suggest that M-2 receptors may have a role in mediating indirect contractions and/or inhibition of detrusor relaxation. In addition, there is evidence that muscarinic receptors located in the urothelium/suburothelium and on afferent nerves may contribute to the pathophysiology of OAB. Blockade of these receptors may also contribute to the clinical efficacy of antimuscarinic agents. 3... (More)
1 The effectiveness of antimuscarinic agents in the treatment of the overactive bladder (OAB) syndrome is thought to arise through blockade of bladder muscarinic receptors located on detrusor smooth muscle cells, as well as on nondetrusor structures. 2 Muscarinic M-3 receptors are primarily responsible for detrusor contraction. Limited evidence exists to suggest that M-2 receptors may have a role in mediating indirect contractions and/or inhibition of detrusor relaxation. In addition, there is evidence that muscarinic receptors located in the urothelium/suburothelium and on afferent nerves may contribute to the pathophysiology of OAB. Blockade of these receptors may also contribute to the clinical efficacy of antimuscarinic agents. 3 Although the role of muscarinic receptors in the bladder, other than M3 receptors, remains unclear, their role in other body systems is becoming increasingly well established, with emerging evidence supporting a wide range of diverse functions. Blockade of these functions by muscarinic receptor antagonists can lead to similarly diverse adverse effects associated with antimuscarinic treatment, with the range of effects observed varying according to the different receptor subtypes affected. 4 This review explores the evolving understanding of muscarinic receptor functions throughout the body, with particular focus on the bladder, gastrointestinal tract, eye, heart, brain and salivary glands, and the implications for drugs used to treat OAB. The key factors that might determine the ideal antimuscarinic drug for treatment of OAB are also discussed. Further research is needed to show whether the M-3 selective receptor antagonists have any advantage over less selective drugs, in leading to fewer adverse events. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
heart, eye, brain, gastrointestinal tract, salivary glands, bladder, M-3 antagonists, selective, antimuscarinics, overactive bladder, muscarinic receptors
in
British Journal of Pharmacology
volume
148
issue
5
pages
565 - 578
publisher
Wiley
external identifiers
  • wos:000238710700003
  • scopus:33745602006
ISSN
1476-5381
DOI
10.1038/sj.bjp.0706780
language
English
LU publication?
yes
id
b963057c-e23d-40b7-9594-de3867748949 (old id 404620)
date added to LUP
2016-04-01 16:26:36
date last changed
2020-12-29 04:40:44
@article{b963057c-e23d-40b7-9594-de3867748949,
  abstract     = {1 The effectiveness of antimuscarinic agents in the treatment of the overactive bladder (OAB) syndrome is thought to arise through blockade of bladder muscarinic receptors located on detrusor smooth muscle cells, as well as on nondetrusor structures. 2 Muscarinic M-3 receptors are primarily responsible for detrusor contraction. Limited evidence exists to suggest that M-2 receptors may have a role in mediating indirect contractions and/or inhibition of detrusor relaxation. In addition, there is evidence that muscarinic receptors located in the urothelium/suburothelium and on afferent nerves may contribute to the pathophysiology of OAB. Blockade of these receptors may also contribute to the clinical efficacy of antimuscarinic agents. 3 Although the role of muscarinic receptors in the bladder, other than M3 receptors, remains unclear, their role in other body systems is becoming increasingly well established, with emerging evidence supporting a wide range of diverse functions. Blockade of these functions by muscarinic receptor antagonists can lead to similarly diverse adverse effects associated with antimuscarinic treatment, with the range of effects observed varying according to the different receptor subtypes affected. 4 This review explores the evolving understanding of muscarinic receptor functions throughout the body, with particular focus on the bladder, gastrointestinal tract, eye, heart, brain and salivary glands, and the implications for drugs used to treat OAB. The key factors that might determine the ideal antimuscarinic drug for treatment of OAB are also discussed. Further research is needed to show whether the M-3 selective receptor antagonists have any advantage over less selective drugs, in leading to fewer adverse events.},
  author       = {Abrams, P and Andersson, Karl-Erik and Buccafusco, JJ and Chapple, C and de Groat, WC and Fryer, AD and Kay, G and Laties, A and Nathanson, NM and Pasricha, PJ and Wein, AJ},
  issn         = {1476-5381},
  language     = {eng},
  number       = {5},
  pages        = {565--578},
  publisher    = {Wiley},
  series       = {British Journal of Pharmacology},
  title        = {Muscarinic receptors: their distribution and function in body systems, and the implications for treating overactive bladder},
  url          = {http://dx.doi.org/10.1038/sj.bjp.0706780},
  doi          = {10.1038/sj.bjp.0706780},
  volume       = {148},
  year         = {2006},
}