Effects of the M3 receptor selective muscarinic antagonist darifenacin on bladder afferent activity of the rat pelvic nerve.
OBJECTIVE
Previous studies have revealed that intravesical and systemic administration of oxybutinin suppress pelvic afferent nerves. This study evaluates the efficacy of a selective M3 antimuscarinic, darifenacin, on bladder afferent activity.


METHODS
Sixteen single bladder afferent fibers were isolated in nine female Sprague-Dawley rats. On the basis of their conduction velocities, they were grouped as Adelta or C fibers. The effect of repeat bladder filling was studied on the mechanosensitive properties of these units. The M3 receptor selective muscarinic antagonist darifenacin (0.1mg/kg) was administered intravenously. Unitary afferent activity was again analyzed 30, 60, 90, and 120 min after the drug administration.


RESULTS
Seven units corresponded to criteria for Adelta fibers, nine for C fibers. Repeat bladder filling did not change nerve activity in Adelta or C fibers. When nerve activity was expressed as a percent of control activity, afferent sensitivity changed after darifenacin in Adelta fibers: 86+/-27%, 30 min (p>0.05), 69 +/- 32%, 60 min (p<0.05), 56 +/- 36%, 90 min (p<0.05), and 61+/- 49%, 120 min (p>0.05), and in C fibers: 70+/-39%, 30 min (p<0.05), 57 +/- 49%, 60 min (p<0.05), 45 +/- 42%, 90 min (p<0.01), and 47 +/- 43%, 120 min (p<0.01).


CONCLUSIONS
In this study we show that darifenacin reduces bladder afferent activity in both Adelta and C fibers. The decrease in afferent spikes in C fibers may be more pronounced than that in Adelta fibers. These results may explain that the efficacy of darifenacin in overactive bladder symptoms is partly due to bladder afferent desensitization.
Iijima
Kazuyoshi
K
Department of Urology, Faculty of Medicine, University Antwerp, Antwerp, Belgium.
De Wachter
Stefan
S
Wyndaele
Jean-Jacques
JJ
D000818:Animals; D001572:Benzofurans / Q000008:administration & dosage*; D005260:Female; D007275:Injections, Intravenous; D018727:Muscarinic Antagonists / Q000008:administration & dosage*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D010388:Pelvis / Q000294:innervation*; D011312:Pressure; D011759:Pyrrolidines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors*; D001743:Urinary Bladder / Q000294:innervation* / Q000502:physiology; D014563:Urodynamics / Q000187:drug effects / Q000502:physiology
D001572:Benzofurans; D018727:Muscarinic Antagonists; D011759:Pyrrolidines; D043587:Receptor, Muscarinic M3; C101207:darifenacin