Muscarinic receptor antagonists in the treatment of overactive bladder.
A wealth of clinical evidence supports the view that muscarinic receptor antagonists are effective in the treatment of overactive bladder. However, treatment-limiting adverse effects such as dry mouth, constipation, and blurred vision have restricted the usefulness of previously available agents, such as oxybutynin. A real need therefore existed for effective and well-tolerated agents for the long-term management of the troublesome symptoms of overactive bladder. This review outlines the various approaches that have been used in attempts to overcome the tolerability problems of oxybutynin. It also describes how advances in our understanding of muscarinic receptors and bladder function has led to the potential development of either tissue- or subtype-selective antimuscarinic agents with improved tolerability. Drugs that have been developed in this way include tolterodine and darifenacin, each of which shows some bladder selectivity in animal models. Unlike darifenacin, however, the bladder selectivity of tolterodine has been confirmed by numerous clinical studies. Tolterodine's improved tolerability compared with oxybutynin, along with its equivalent therapeutic efficacy at recommended dosages, permits patients to experience the beneficial effects of long-term treatment. Tolterodine therefore represents a real alternative for the long-term management of overactive bladder. The results of ongoing clinical studies with darifenacin are awaited before it can be concluded that selective antagonism of M(3) receptors leads to improved tolerability over existing agents in the treatment of overactive bladder. Similarly, the potential improvements in tolerability associated with different dosage formulations of oxybutynin, and the clinical utility of S-oxybutynin, are yet to be conclusively demonstrated.
Chapple
C R
CR
Department of Urology, The Royal Hallamshire Hospital, Glossop Road, Sheffield, United Kingdom.
D001559:Benzhydryl Compounds / Q000627:therapeutic use; D001572:Benzofurans / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003408:Cresols / Q000627:therapeutic use; D006801:Humans; D008333:Mandelic Acids / Q000627:therapeutic use*; D018727:Muscarinic Antagonists / Q000627:therapeutic use*; D010665:Phenylpropanolamine; D011759:Pyrrolidines / Q000627:therapeutic use; D000068737:Tolterodine Tartrate; D001745:Urinary Bladder Diseases / Q000150:complications* / Q000188:drug therapy*; D014549:Urinary Incontinence / Q000150:complications* / Q000188:drug therapy*
D001559:Benzhydryl Compounds; D001572:Benzofurans; D003408:Cresols; D008333:Mandelic Acids; D018727:Muscarinic Antagonists; D011759:Pyrrolidines; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate; C101207:darifenacin; C005419:oxybutynin