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.