Evaluation of the Potential Inhibitory Effects of Medications for Detrusor Overactivity on Platelet-Activating Factor (PAF)-Induced Mechanical Activity in Guinea Pig Bladder Smooth Muscle

This study aimed to determine whether currently available medications for detrusor overactivity (DO) can inhibit the platelet-activating factor (PAF)-induced increase in the mechanical activity of the urinary bladder smooth muscle (UBSM) in guinea pigs. Ten clinically used DO drugs-oxybutynin, tolterodine, fesoterodine, propiverine, propantheline, solifenacin, imidafenacin, flavoxate, urapidil, and clenbuterol-were tested at a concentration of 10 μM, exceeding typical therapeutic plasma levels. Among these, oxybutynin exerted the most pronounced inhibitory effect, reducing the PAF (1 μM)-induced increase in basal tone by approximately 60%. Furthermore, oxybutynin (10 μM) also decreased 60 mM KCl-induced contractions by a similar extent and nearly abolished acetylcholine (ACh, 10 μM)-induced contractions. These findings suggest that oxybutynin suppresses PAF-induced UBSM hyperactivity through a mechanism distinct from its anticholinergic effect, likely mediated by blockade of voltage-dependent Ca²⁺ channels (VDCCs).