Muscarinic receptor antagonists for overactive bladder

作者: Paul Abrams , Karl-Erik Andersson

DOI: 10.1111/J.1464-410X.2007.07205.X

关键词:

摘要: Overactive bladder (OAB) is a syndrome characterized by urinary urgency, with or without urgency incontinence, usually frequency and nocturia. OAB symptoms are often associated detrusor overactivity (DO). Like symptoms, the prevalence of DO increases age can have neurogenic and/or myogenic aetiology. Bladder outlet obstruction be contributing factor in DO, possibly through cholinergic denervation supersensitivity muscarinic receptors to acetylcholine, although similar men women across groups. Acetylcholine primary contractile neurotransmitter human detrusor, antimuscarinics exert their effects on OAB/DO inhibiting binding acetylcholine at M(2) M(3) smooth muscle cells other structures within wall. Worldwide, there six antimuscarinic drugs currently marketed for treatment OAB: oxybutynin, tolterodine, propiverine, trospium, darifenacin, solifenacin. Each has demonstrated efficacy but pharmacokinetic adverse event profiles differ somewhat due structural differences (tertiary vs quaternary amines), receptor subtype selectivities, organ selectivities. Antimuscarinics generally well tolerated, even special populations (e.g. obstruction, elderly patients, children). The most frequently reported events clinical studies dry mouth, constipation, headache, blurred vision; few patients withdraw from trials because events. Development an functional selectivity would reduce occurrence therapeutic potential several agents, such as alpha(3)-adrenoceptor agonists, purinergic antagonists, phosphodiesterase inhibitors, neurokinin-1 opioids, Rho-kinase also under investigation OAB.

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