Antimuscarinics for the treatment of overactive bladder: understanding the role of muscarinic subtype selectivity

INTRODUCTION AND HYPOTHESIS: Antimuscarinic agents appear to exert their therapeutic activity in overactive bladder (OAB) via blockade of the M(3) muscarinic receptor subtype. Antimuscarinics are broadly similar in efficacy, but their safety and tolerability profiles vary, which may reflect differences in muscarinic receptor selectivity profiles. METHODS: This review of available literature aims to determine whether antimuscarinic agents with greater M(3) selectivity have clinical advantages over less selective drugs. RESULTS: Antimuscarinic agents differ widely in their propensity to cause cognitive and cardiovascular (CV) effects, which appear mainly to be related to differences in their relative selectivity for binding to non-M(3) receptors, including M(1) receptors in the brain and cardiac M(2) receptors. CONCLUSIONS: Cognitive and CV effects are especially pertinent for the OAB patient who tends to be older with various comorbidities and is often taking multiple medications. Hence, it is important to consider the risk/benefit balance of antimuscarinic agents when selecting OAB treatment.