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CNS involvement in overactive bladder: pathophysiology and opportunities for pharmacological intervention.

Andersson, Karl-Erik LU and Pehrson, Rikard LU (2003) In Drugs 63(23). p.2595-2611
Abstract
The pathophysiology of overactive bladder (OAB) syndrome is complex, and involves both peripheral and CNS factors. Several CNS disorders are associated with OAB, e.g. stroke, spinal cord injury, Parkinson’s disease and multiple sclerosis, and in each disorder the pathophysiology of OAB can be multifactorial. Irrespective of cause or pathophysiology of OAB, antimuscarinic drugs are the first line of pharmacological treatment. However, adverse effects and limited efficacy makes alternative therapeutic principles desirable. Most alternative drugs used for the treatment of OAB have a peripheral site of action, mainly affecting efferent or afferent neurotransmission or the detrusor muscle itself. New targets for pharmacological intervention may... (More)
The pathophysiology of overactive bladder (OAB) syndrome is complex, and involves both peripheral and CNS factors. Several CNS disorders are associated with OAB, e.g. stroke, spinal cord injury, Parkinson’s disease and multiple sclerosis, and in each disorder the pathophysiology of OAB can be multifactorial. Irrespective of cause or pathophysiology of OAB, antimuscarinic drugs are the first line of pharmacological treatment. However, adverse effects and limited efficacy makes alternative therapeutic principles desirable. Most alternative drugs used for the treatment of OAB have a peripheral site of action, mainly affecting efferent or afferent neurotransmission or the detrusor muscle itself. New targets for pharmacological intervention may be found in the CNS.



Several CNS transmitters/transmitter systems are known to be involved in micturition control, but few drugs with a defined CNS site of action (e.g. baclofen, imipramine and duloxetine) have been used for the treatment of voiding disorders. GABA, glutamate, opioid, serotonin, noradrenaline (norepinephrine), and dopamine receptors and mechanisms are known to influence micturition, and drugs influencing these systems could potentially be developed for the treatment of OAB.



Preclinical studies in different animal models have shown that modulation of normal micturition and detrusor overactivity by drugs acting within the spinal cord or supraspinally is possible. Promising results have been obtained in such models, e.g. with drugs interfering with GABA mechanisms, serotonin 5-HT1A receptors, mu-opioid receptors and alpha-adrenoreceptors. However, considering the limited predictability of existing animal models for efficacy in humans, positive proof of concept studies in humans are mandatory. Such studies are scarce and further investigations are needed. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Detrusor instability, Baclofen, therapeutic use, Duloxetine, Research and development, Bladder dysfunction
in
Drugs
volume
63
issue
23
pages
2595 - 2611
publisher
Adis International
external identifiers
  • wos:000186917000003
  • pmid:14636079
  • scopus:0344082701
ISSN
0012-6667
language
English
LU publication?
yes
id
2d0c72e3-a628-4807-ab15-f7a2d010b62b (old id 118676)
alternative location
http://www.ingentaconnect.com/content/adis/dgs/2003/00000063/00000023/art00003
date added to LUP
2007-07-04 15:11:35
date last changed
2018-01-07 09:45:25
@article{2d0c72e3-a628-4807-ab15-f7a2d010b62b,
  abstract     = {The pathophysiology of overactive bladder (OAB) syndrome is complex, and involves both peripheral and CNS factors. Several CNS disorders are associated with OAB, e.g. stroke, spinal cord injury, Parkinson’s disease and multiple sclerosis, and in each disorder the pathophysiology of OAB can be multifactorial. Irrespective of cause or pathophysiology of OAB, antimuscarinic drugs are the first line of pharmacological treatment. However, adverse effects and limited efficacy makes alternative therapeutic principles desirable. Most alternative drugs used for the treatment of OAB have a peripheral site of action, mainly affecting efferent or afferent neurotransmission or the detrusor muscle itself. New targets for pharmacological intervention may be found in the CNS.<br/><br>
<br/><br>
Several CNS transmitters/transmitter systems are known to be involved in micturition control, but few drugs with a defined CNS site of action (e.g. baclofen, imipramine and duloxetine) have been used for the treatment of voiding disorders. GABA, glutamate, opioid, serotonin, noradrenaline (norepinephrine), and dopamine receptors and mechanisms are known to influence micturition, and drugs influencing these systems could potentially be developed for the treatment of OAB.<br/><br>
<br/><br>
Preclinical studies in different animal models have shown that modulation of normal micturition and detrusor overactivity by drugs acting within the spinal cord or supraspinally is possible. Promising results have been obtained in such models, e.g. with drugs interfering with GABA mechanisms, serotonin 5-HT1A receptors, mu-opioid receptors and alpha-adrenoreceptors. However, considering the limited predictability of existing animal models for efficacy in humans, positive proof of concept studies in humans are mandatory. Such studies are scarce and further investigations are needed.},
  author       = {Andersson, Karl-Erik and Pehrson, Rikard},
  issn         = {0012-6667},
  keyword      = {Detrusor instability,Baclofen,therapeutic use,Duloxetine,Research and development,Bladder dysfunction},
  language     = {eng},
  number       = {23},
  pages        = {2595--2611},
  publisher    = {Adis International},
  series       = {Drugs},
  title        = {CNS involvement in overactive bladder: pathophysiology and opportunities for pharmacological intervention.},
  volume       = {63},
  year         = {2003},
}