Darifenacin: a selective M3 muscarinic receptor antagonist for the treatment of overactive bladder

Phillip P Smith, H Henry Lai and Rodney A Appell

Overactive bladder is a common and distressing disorder that imposes significant financial and quality-of-life costs. The current therapeutic paradigm aims to decrease detrusor overactivity via blockade of bladder M3 muscarinic receptors, the primary cholinergic receptors responsible for detrusor contraction. However, systemic antimuscarinic adverse effects, such as dry mouth and constipation, limit the tolerability of antimuscarinic treatment. Therefore, a uroselective M3 receptor antagonist would be considered optimal therapy for overactive bladder. Darifenacin (Enablex®) is the most recent antimuscarinic drug approved for the treatment of overactive bladder. It demonstrates M3 receptor selectivity, but is not M3 specific. Despite animal data suggesting uroselectivity, it is not sufficiently uroselective in therapeutic use. While effective in reducing symptoms related to overactive bladder, dry mouth and constipation remain common. There are no comparative trials comparing darifenacin with existing agents, therefore it is not known if darifenacin represents an improvement over existing agents.