Antimuscarinic Mechanisms and the Overactive Detrusor: An Update

Andersson, Karl‐Erik

doi:10.1016/j.eururo.2010.11.040

Cited by 143 publications

(96 citation statements)

References 111 publications

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“…All the muscarinic receptor subtypes are found in the urothelium and suburothelium, with predominant expression of M 2 , M 3 receptors (11,15,51). The density of M 2 and M 3 receptors in the LP were found to be increased in the bladders of patient with IDO and BPS/IC, and there was a correlation between suburothelial muscarinic receptor density and urgency scores (211).…”

Section: F Muscarinic Receptor Antagonistsmentioning

confidence: 91%

“…A focus of current LUT research has been afferent mechanisms and the processes of how afferent information is generated and conveyed to the CNS in the control of micturition (11,13,153). One of the pathways defined involves the bladder mucosa, but attention has been given mainly to the urothelium (38).…”

Section: Lamina Propriamentioning

confidence: 99%

“…However, where the afferent impulses for bladder sensation and bladder activation are generated, and by what mechanisms, have not been fully established. However, at least two afferent signaling systems can be defined: the myogenic and mucosal pathways (11,12). Bladder filling increases activity in in-series-coupled low-threshold mechanoreceptive afferents, thereby initiating activation of the micturition reflex.…”

Section: Introductionmentioning

confidence: 99%

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Urothelial Signaling

Birder

Andersson

2013

Physiological Reviews

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388

362

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The urothelium, which lines the inner surface of the renal pelvis, the ureters, and the urinary bladder, not only forms a high-resistance barrier to ion, solute and water flux, and pathogens, but also functions as an integral part of a sensory web which receives, amplifies, and transmits information about its external milieu. Urothelial cells have the ability to sense changes in their extracellular environment, and respond to chemical, mechanical and thermal stimuli by releasing various factors such as ATP, nitric oxide, and acetylcholine. They express a variety of receptors and ion channels, including P2X3 purinergic receptors, nicotinic and muscarinic receptors, and TRP channels, which all have been implicated in urothelial-neuronal interactions, and involved in signals that via components in the underlying lamina propria, such as interstitial cells, can be amplified and conveyed to nerves, detrusor muscle cells, and ultimately the central nervous system. The specialized anatomy of the urothelium and underlying structures, and the possible communication mechanisms from urothelial cells to various cell types within the bladder wall are described. Changes in the urothelium/ lamina propria ("mucosa") produced by different bladder disorders are discussed, as well as the mucosa as a target for therapeutic interventions.

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Section: F Muscarinic Receptor Antagonistsmentioning

confidence: 91%

Section: Lamina Propriamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Urothelial Signaling

Birder

Andersson

2013

Physiological Reviews

Self Cite

388

362

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“…4 Later meta-analyses have reported that anticholinergic drugs are efficacious, safe, tolerable and improve quality of life. [5][6][7] The main side-effects of anticholinergics are dry mouth/eyes, constipation and 8,9 This may also explain how these drugs can help with urinary urgency, which is probably a sensory phenomenon.…”

Section: Medical Therapymentioning

confidence: 99%

Overactive bladder in men: treatment options

Birch

Dowson

Seth

et al. 2012

Trends Urol & Men's Health

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“…However, antimuscarinics were also shown to act during the storage phase of micturition reflex reducing the afferent input to the central nervous system. 2 Consequently, basic science and clinical research is trying to address issues of efficacy, tolerability and convenience of new therapeutic strategies targeting the 'afferent' function.…”

Section: Introductionmentioning

confidence: 99%

Controversy over the pharmacological treatments of storage symptoms in spinal cord injury patients: a literature overview

et al. 2011

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Study design: Our aim was to locate research and communicate the evidence found from scientific studies pertaining to the treatment of neurogenic detrusor overactivity (NDO) in the chronic stage of spinal cord injury (SCI). Objective: To address the controversy over the traditional (antimuscarinics) and the 'new' treatments for NDO and try to offer an insight on the rationale underlying the development of new drugs such as botulinum toxin (BTX), vanilloids, nociceptin/orphanin FQ. As a final point, to provide information on a new class of cation channels, the Degenerin/Epithelial Na + Channel (Deg/ENaC) Family that could be future targets for the management of NDO. Setting: International. Methods: Overview of English literature on drug management of NDO. Results: Agents that block the 'efferent' function of micturition reflex, such as antimuscarinics, are currently first-line therapy for NDO. They reach the highest level of evidence (1a) and grade of recommendation (A). However, many patients and physicians believe that the 'efferent' pharmacological management of NDO is not completely satisfactory. Consequently, research is trying to address issues of efficacy, tolerability and convenience of new therapeutic strategies targeting the 'afferent' function. Conclusion: Antimuscarinic therapy increases the bladder capacity and delays the initial urge to void. However, in some patients they fail to achieve the patient's therapeutic goals. New interesting approaches have been investigated in the last few years. BTX seems to be very promising in treating neurogenic overactive bladder (OAB), but other compounds are now on the horizon.

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Antimuscarinic Mechanisms and the Overactive Detrusor: An Update

Cited by 143 publications

References 111 publications

Urothelial Signaling

Urothelial Signaling

Overactive bladder in men: treatment options

Controversy over the pharmacological treatments of storage symptoms in spinal cord injury patients: a literature overview

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