Darifenacin, in particular, is a commonly prescribed antimuscarinic selective to M3 receptors, the main muscarinic receptor subtype responsible for contraction. Darifenacin also appears to be more effective on bladder tissue compared to other tissues.3
There is very little current literature on darifenacin, and it appears that novel studies investigating darifenacin in OAB have been dwindling. Although this drug was approved for use over 20 years ago, its continued and widespread use presents importance towards continued investigations into its mechanisms, clinical use, and side effects. Of particular note is that patients taking darifenacin have a reported low rate of long-term persistence, ranging from 12- 34.3%.4,5
Our study identified novel non-muscarinic-induced contractions in the bladder that were inhibited by darifenacin.6 This was identified using strips of paired juvenile and adult porcine urothelium with lamina propria, or detrusor smooth muscle, in isolated tissue baths.7 Experiments in the presence of darifenacin (100 nM) were completed with serotonin (5-HT, 100 μM), prostaglandin E2 (PGE2, 10 μM), histamine (100 μM), αβ-methylene-ATP (αβm-ATP, 10 μM), angiotensin II (AII, 100 nM), neurokinin A (NKA, 300 nM), and carbachol (10 μM). Different mechanisms were identified for each tissue.
Darifenacin significantly reduced maximum contractile responses to carbachol in adult detrusor preparations by 46%, αβm-ATP by 50%, PGE2 by 73%, histamine by 64%, and 5HT by 53%. Darifenacin reduced the maximum contraction in adult U&LP preparations to carbachol by 49% and to αβm-ATP by 35%. Studies of 5HT, PGE2, histamine, and αβm-ATP were also repeated with darifenacin in the presence of atropine (1 μM), where they maintained contractions, suggesting that the influence of darifenacin on these agonists was independent of muscarinic receptor mechanisms. In juvenile preparations, a separate mechanism independent of the receptors assessed is thought to be involved and presents an interesting direction for future studies. The overall results suggest that darifenacin influences non-muscarinic pathways in urinary bladder tissue, indicating its potential to assist OAB patients presenting with a pathology that is not related to muscarinic receptor mechanisms.
Written by: Vineesha Veer, BBiomedSc (Hons), Russ Chess-Williams, PhD, and Christian Moro, PhD
- Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Australia
- Chuang Y-C, Liu S-P, Lee K-S, Liao L, Wang J, Yoo TK, et al. Prevalence of overactive bladder in China, Taiwan and South Korea: Results from a cross-sectional, population-based study. Low Urin Tract Symptoms. 2019;11(1):48-55.
- Stewart WF, Van Rooyen JB, Cundiff GW, Abrams P, Herzog AR, Corey R, et al. Prevalence and burden of overactive bladder in the United States. World journal of urology. 2003;20(6):327-36.
- Yamada S, Kuraoka S, Osano A, Ito Y. Characterization of bladder selectivity of antimuscarinic agents on the basis of in vivo drug-receptor binding. International Neurourology Journal. 2012;16(3):107-15.
- Wagg A, Compion G, Fahey A, Siddiqui E. Persistence with prescribed antimuscarinic therapy for overactive bladder: a UK experience. BJU International. 2012;110(11):1767-74.
- Mauseth SA, Skurtveit S, Spigset O. Adherence, persistence and switch rates for anticholinergic drugs used for overactive bladder in women: data from the Norwegian Prescription Database. Acta Obstetricia et Gynaecologica Scandinavica. 2013;92(10):1208-15.
- Veer V, Russ C-W, Christian M. Comparisons of urinary bladder responses to common antimuscarinics reveals unique effects of darifenacin. Front physiol. 2025;16:1534517.
- Veer V, Chess-William R, Moro C. Antimuscarinic actions on bladder urothelium and lamina propria contractions are similar to those observed in detrusor smooth muscle preparations. Neurourol Urodyn. 2023;42(5):1080-7.