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.
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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)
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Copyright | European Association of Urology. |
Chemical References |
- Benzofurans
- Muscarinic Antagonists
- Pyrrolidines
- Receptor, Muscarinic M3
- darifenacin
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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)
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