The inhibitory effect of trimetazidine on detrusor contractility – a potential repositioning of trimetazidine for the treatment of overactive bladder. (10th June 2021)

• Record Type: Journal Article
• Authors: Engin, Seckin; Kaya Yasar, Yesim; Barut, Elif Nur; Getboga, Damla; Erac, Yasemin; Sezen, Sena F
• Is Part Of: Journal of pharmacy and pharmacology. Volume 74:Number 1(2022)
• Page Start: 94
• Page End: 102
• Publication Date: 2021-06-10
• Subjects: calcium -- detrusor -- ion channels -- isolated tissue bath -- fura-2 -- trimetazidine; Pharmacy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1093/jpp/rgab072
• Languages: English
• ISSNs: 0022-3573

Abstract

Abstract: Objectives: This study aimed to identify the effect of trimetazidine (TMZ), an antianginal drug, on detrusor smooth muscle (DSM) contractility and its possible mechanisms of action. Methods: We performed in-vitro contractility studies on isolated mouse DSM strips and investigated the effect of TMZ on Ca 2+ levels in fura-2-loaded A7r5 cells. Key findings: TMZ (300 or 1000 µM) inhibited carbachol (CCh)- and KCl-induced contractions and produced a concentration-dependent (10–1000 µM) relaxation in KCl-precontracted DSM strips. TMZ-induced relaxation was markedly decreased by BaCl2, an inward-rectifying K + channel blocker, but was not altered by preincubation with tetraethylammonium, glibenclamide, 4-aminopyridine, propranolol, L-NAME or methylene blue. TMZ (300 or 1000 µM) reduced both the CaCl2 -induced contraction of depolarized DSM strips under Ca 2+ -free conditions and the CCh-induced contraction of DSM strips preincubated with nifedipine in Ca 2+ -containing Krebs solution. Furthermore, TMZ (1000 µM) significantly decreased the Ca 2+ levels in fura-2-loaded A7r5 cells. Conclusions: TMZ decreased DSM contractility and caused a concentration-dependent relaxation of the tissue possibly through its actions on Ca 2+ transients and K + channels. Our results provide preclinical evidence that TMZ would be a potential candidate to treat disorders related to the overactivity of the bladder.