Darifenacin is a novel M3
muscarinic selective receptor antagonist for once-daily treatment of
overactive bladder (OAB), a highly prevalent, chronic and debilitating disease defined by urinary urgency with or without
urge incontinence, usually with increased frequency of micturition and
nocturia. In vitro,
darifenacin is a potent and specific
muscarinic receptor antagonist with </= 59-fold higher selectivity for
muscarinic M3 receptors relative to other
muscarinic receptor subtypes. This profile may, therefore, confer clinical efficacy in the treatment of OAB, with a lower propensity for adverse effects and safety issues related to blockade of other
muscarinic receptor subtypes. Indeed, consistent with its low relative affinity for M1 and M2 receptors, no effects on cognitive function and heart-rate variability, respectively, have been observed with
darifenacin. Subsequent large-scale clinical trials have confirmed that
darifenacin (at doses of 7.5 and 15 mg/day) results in central nervous system and cardiac adverse events comparable to placebo, and provides early and meaningful improvement across a range of OAB symptoms including incontinence episodes, urgency and urinary frequency. On the basis of such findings,
darifenacin would appear to meet the current need for an effective OAB
pharmacotherapy that is efficacious, well-tolerated and, more importantly, minimises the risk of safety-related adverse effects.