Muscarinic receptor antagonists for overactive bladder.
Article Details
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Abrams P, Andersson KE
Muscarinic receptor antagonists for overactive bladder.
BJU Int. 2007 Nov;100(5):987-1006. doi: 10.1111/j.1464-410X.2007.07205.x.
- PubMed ID
- 17922784 [ View in PubMed]
- Abstract
Overactive bladder (OAB) is a syndrome characterized by urinary urgency, with or without urgency urinary incontinence, usually with frequency and nocturia. OAB symptoms are often associated with detrusor overactivity (DO). Like OAB symptoms, the prevalence of DO increases with age and can have a neurogenic and/or myogenic aetiology. Bladder outlet obstruction can be a contributing factor in DO, possibly through cholinergic denervation of the detrusor and supersensitivity of muscarinic receptors to acetylcholine, although the prevalence of OAB is similar in men and women across age groups. Acetylcholine is the primary contractile neurotransmitter in the human detrusor, and antimuscarinics exert their effects on OAB/DO by inhibiting the binding of acetylcholine at muscarinic receptors M(2) and M(3) on detrusor smooth muscle cells and other structures within the bladder wall. Worldwide, there are six antimuscarinic drugs currently marketed for the treatment of OAB: oxybutynin, tolterodine, propiverine, trospium, darifenacin, and solifenacin. Each has demonstrated efficacy for the treatment of OAB symptoms, but their pharmacokinetic and adverse event profiles differ somewhat due to structural differences (tertiary vs quaternary amines), muscarinic receptor subtype selectivities, and organ selectivities. Antimuscarinics are generally well tolerated, even in special populations (e.g. men with bladder outlet obstruction, elderly patients, children). The most frequently reported adverse events in clinical studies of antimuscarinics are dry mouth, constipation, headache, and blurred vision; few patients withdraw from clinical trials because of adverse events. Development of an antimuscarinic with functional selectivity for the bladder would reduce the occurrence of antimuscarinic adverse events. The therapeutic potential of several other agents, such as alpha(3)-adrenoceptor agonists, purinergic receptor antagonists, phosphodiesterase inhibitors, neurokinin-1 receptor antagonists, opioids, and Rho-kinase inhibitors, is also under investigation for the treatment of OAB.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Methantheline Muscarinic acetylcholine receptor M2 Protein Humans UnknownNot Available Details Methantheline Muscarinic acetylcholine receptor M3 Protein Humans UnknownNot Available Details - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAlloinTramadol The therapeutic efficacy of Alloin can be decreased when used in combination with Tramadol. AlloinTrospium The therapeutic efficacy of Alloin can be decreased when used in combination with Trospium. AlloinOxyphenonium The therapeutic efficacy of Alloin can be decreased when used in combination with Oxyphenonium. AlloinBenzatropine The therapeutic efficacy of Alloin can be decreased when used in combination with Benzatropine. AlloinZiprasidone The therapeutic efficacy of Alloin can be decreased when used in combination with Ziprasidone.