title: Pharmacodynamic effects of darifenacin, a muscarinic M selective receptor antagonist for the treatment of overactive bladder, in healthy volunteers.
abstract: OBJECTIVE
  To evaluate the pharmacodynamic effects of darifenacin (a muscarinic M(3) selective receptor antagonist) and dicyclomine (an M(1) selective receptor antagonist) in healthy male volunteers.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Darifenacin did not affect cognitive, cardiac or visual function in healthy volunteers, a profile that may reflect its relative M(3) receptor selectivity and M(1)/M(2) sparing properties.
authors.affiliation: Washington Neuropsychological Institute, Washington, DC 20008, USA. gkay@tidalwave.net
authors.forename: Gary G
authors.initials: GG
authors.lastname: Kay
authors.forename: Keith A
authors.initials: KA
authors.lastname: Wesnes
mesh_terms: D000328:Adult; D001572:Benzofurans / Q000494:pharmacology* / Q000627:therapeutic use; D003071:Cognition / Q000187:drug effects*; D018592:Cross-Over Studies; D004025:Dicyclomine / Q000627:therapeutic use; D004311:Double-Blind Method; D005062:European Union; D006801:Humans; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D011759:Pyrrolidines / Q000494:pharmacology* / Q000627:therapeutic use; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors*; D012472:Salivation / Q000187:drug effects; D012815:Signal Processing, Computer-Assisted; D013997:Time Factors; D014549:Urinary Incontinence / Q000188:drug therapy* / Q000523:psychology
chemical_list: D001572:Benzofurans; D018727:Muscarinic Antagonists; D011759:Pyrrolidines; D043587:Receptor, Muscarinic M3; D004025:Dicyclomine; C101207:darifenacin