Effects of the M3 receptor selective muscarinic antagonist darifenacin on bladder afferent activity of the rat pelvic nerve.

Abstract

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.

• Authors: Kazuyoshi Iijima, Stefan De Wachter, Jean-Jacques Wyndaele
• Journal: European urology (Eur Urol) Vol. 52 Issue 3 Pg. 842-7 (Sep 2007) ISSN: 0302-2838 [Print] Switzerland
• PMID: 17360104 (Publication Type: Journal Article)
• Copyright: European Association of Urology.

Chemical References

• Benzofurans
• Muscarinic Antagonists
• Pyrrolidines
• Receptor, Muscarinic M3
• darifenacin

Topics

• Animals
• Benzofurans (administration & dosage)
• Female
• Injections, Intravenous
• Muscarinic Antagonists (administration & dosage)
• Neurons, Afferent (drug effects, physiology)
• Pelvis (innervation)
• Pressure
• Pyrrolidines (administration & dosage)
• Rats
• Rats, Sprague-Dawley
• Receptor, Muscarinic M3 (antagonists & inhibitors)
• Urinary Bladder (innervation, physiology)
• Urodynamics (drug effects, physiology)