Pharmacodynamic effects of darifenacin, a muscarinic M3 selective receptor antagonist for the treatment of overactive bladder, in healthy volunteers
Article first published online: 13 OCT 2005
Volume 96, Issue 7, pages 1055–1062, November 2005
How to Cite
Kay, G. G. and Wesnes, K. A. (2005), Pharmacodynamic effects of darifenacin, a muscarinic M3 selective receptor antagonist for the treatment of overactive bladder, in healthy volunteers. BJU International, 96: 1055–1062. doi: 10.1111/j.1464-410X.2005.05745.x
- Issue published online: 13 OCT 2005
- Article first published online: 13 OCT 2005
- Accepted for publication 10 June 2005
- overactive bladder;
- cognitive function;
- heart rate
To evaluate the pharmacodynamic effects of darifenacin (a muscarinic M3 selective receptor antagonist) and dicyclomine (an M1 selective receptor antagonist) in healthy male volunteers.
SUBJECTS AND METHODS
In this double-blind, four-way crossover study, 27 healthy men (aged 19–44 years) were randomized to receive darifenacin 7.5 mg or 15 mg once daily, dicyclomine 20 mg four times daily or matching placebo. Each 7-day treatment period was separated by a 7-day washout. Multiple assessments of cognitive function, quantitative electroencephalogram (EEG) recordings, salivation, visual nearpoint, heart rate and heart rate variability were made on day 7 in each treatment period.
Compared with placebo, neither dose of darifenacin affected cognitive function, whereas dicyclomine impaired performance on five of the 12 variables 2 h after dosing; simple reaction time (P = 0.009), speed of numeric (P = 0.012) and spatial (P = 0.048) working memory, and speed (P = 0.04) and sensitivity (P = 0.03) of picture recognition. These cognitive changes were accompanied by slowing of the EEG for dicyclomine. Darifenacin showed no clinically relevant effect on EEG. Darifenacin 7.5 and 15 mg once daily did not differ from placebo in effects on visual nearpoint, heart rate or heart rate variability. By contrast, dicyclomine significantly increased the maximum visual nearpoint, decreased heart rate and increased heart rate variability, relative to placebo. Both agents decreased salivary flow rate vs placebo. Treatment-related adverse events were comparable in all groups, the most common being dry mouth; none led to treatment discontinuation.
Darifenacin did not affect cognitive, cardiac or visual function in healthy volunteers, a profile that may reflect its relative M3 receptor selectivity and M1/M2 sparing properties.