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ORIGINAL RESEARCH article

Front. Physiol.
Sec. Renal Physiology and Pathophysiology
Volume 16 - 2025 | doi: 10.3389/fphys.2025.1534517

Comparisons of urinary bladder responses to common antimuscarinics used for the treatment of overactive bladder revealed unique effects of darifenacin on non-muscarinic actions

Provisionally accepted
Vineesha Veer Vineesha Veer Russ Chess-Williams Russ Chess-Williams Christian Moro Christian Moro *
  • Bond University, Gold Coast, Australia

The final, formatted version of the article will be published soon.

    Antimuscarinics are the first-line pharmaceutical treatment for overactive bladder (OAB). Some literature suggests responses to the antimuscarinics can influence a variety of non-muscarinic receptors. This study aimed to identify any non-muscarinic influences on contraction from commonly prescribed clinical antimuscarinics using porcine detrusor or urothelium with lamina propria (U&LP) tissues. Porcine bladders were dissected into strips of juvenile or adult detrusor or U&LP. Carbachol concentration-response curves were performed on paired tissues in the absence or presence of commonly prescribed antimuscarinics; darifenacin, fesoterodine, oxybutynin, solifenacin, trospium and tolterodine. Estimated affinities for each antimuscarinic were calculated and maximum contraction values from control and intervention curves were compared. Experiments in the presence of darifenacin (100nM) were completed with serotonin (100µM), prostaglandin E2 (10µM), histamine (100µM), αβ-methylene-ATP (10µM), angiotensin II (100nM), neurokinin A (300nM) and carbachol (10µM). Darifenacin significantly reduced maximum contraction response in adult detrusor preparations to carbachol by 46%, αβ-methylene-ATP by 50%, prostaglandin E2 by 73%, histamine by 64%, and serotonin by 43%. Maximum contraction was reduced by darifenacin in adult U&LP preparations to carbachol by 49% and αβ-methylene-ATP by 35%. Darifenacin presents as an antimuscarinic medication that influences non-muscarinic pathways in urinary bladder tissue, indicating its potential to assist OAB patients with non-muscarinic pathophysiology.

    Keywords: Urinary Bladder, Bladder pathology, Bladder disease, Acetylcholine, muscarinic receptor

    Received: 26 Nov 2024; Accepted: 14 Jan 2025.

    Copyright: © 2025 Veer, Chess-Williams and Moro. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Christian Moro, Bond University, Gold Coast, Australia

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