Muscarinic receptor subtypes and management of the overactive bladder

Christopher R. Chapple, Tomonori Yamanishi, Russell Chess-Williams

Research output: Contribution to journalArticleResearchpeer-review

110 Citations (Scopus)

Abstract

Anticholinergic agents are the most widely used therapy for urge incontinence despite exerting adverse effects, such as constipation, tachycardia, and dry mouth, that limit their use. These adverse effects result from a lack of selectivity for the bladder over other organs. Although M2-muscarinic receptors are the predominant cholinoreceptor present in urinary bladder, the smaller population of M3-receptors appears to be the most functionally important and mediates direct contraction of the detrusor muscle. M2-receptors modulate detrusor contraction by several mechanisms and may contribute more to contraction of the bladder in pathologic states, such as bladder denervation or spinal cord injury. Prejunctional inhibitory M2-receptors or M4-receptors and prejunctional facilitatory M1-muscarinic receptors in the bladder have also been reported, but their relevance to the clinical effectiveness of muscarinic antagonists is unknown. In clinical studies, tolterodine, a nonselective muscarinic antagonist, has been reported to be equally effective to oxybutynin but to induce less dry mouth. Controlled-release and intravesical, intravaginal, and rectal administrations of oxybutynin have all been reported to cause fewer adverse effects. Conversely, darifenacin, a new M3-selective antagonist, has been reported to have selectivity for the bladder over the salivary gland in vivo. Whether M3-selective or nonselective muscarinic antagonists will be the most clinically effective for the overactive bladder - preserving the best balance between efficacy and tolerability - has yet to be established, and comparative clinical trials between compounds, such as darifenacin (M3 selective) and tolterodine (nonselective) will be required.

Original languageEnglish
Pages (from-to)82-89
Number of pages8
JournalUrology
Volume60
Issue number5 SUPPL. 1
DOIs
Publication statusPublished - 1 Nov 2002
Externally publishedYes

Fingerprint

Overactive Urinary Bladder
Muscarinic Receptors
Urinary Bladder
Muscarinic Antagonists
Mouth
Intravaginal Administration
Muscarinic M2 Receptors
Muscarinic M1 Receptors
Rectal Administration
Intravesical Administration
Urge Urinary Incontinence
Cholinergic Antagonists
Denervation
Constipation
Muscle Contraction
Salivary Glands
Spinal Cord Injuries
Tachycardia
Clinical Trials
Population

Cite this

Chapple, Christopher R. ; Yamanishi, Tomonori ; Chess-Williams, Russell. / Muscarinic receptor subtypes and management of the overactive bladder. In: Urology. 2002 ; Vol. 60, No. 5 SUPPL. 1. pp. 82-89.
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Muscarinic receptor subtypes and management of the overactive bladder. / Chapple, Christopher R.; Yamanishi, Tomonori; Chess-Williams, Russell.

In: Urology, Vol. 60, No. 5 SUPPL. 1, 01.11.2002, p. 82-89.

Research output: Contribution to journalArticleResearchpeer-review

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