The inhibitory effect of trimetazidine on detrusor contractility - a potential repositioning of trimetazidine for the treatment of overactive bladder.

Autor:	Engin S; Department of Pharmacology, Faculty of Pharmacy, Karadeniz Technical University, Trabzon, Turkey., Kaya Yasar Y; Department of Pharmacology, Faculty of Pharmacy, Karadeniz Technical University, Trabzon, Turkey.; Drug and Pharmaceutical Technology Application and Research Center, Karadeniz Technical University, Trabzon, Turkey., Barut EN; Department of Pharmacology, Faculty of Pharmacy, Karadeniz Technical University, Trabzon, Turkey., Getboga D; Department of Pharmacology, Faculty of Pharmacy, Ege University, İzmir, Turkey., Erac Y; Department of Pharmacology, Faculty of Pharmacy, Ege University, İzmir, Turkey., Sezen SF; Department of Pharmacology, Faculty of Pharmacy, Karadeniz Technical University, Trabzon, Turkey.; Drug and Pharmaceutical Technology Application and Research Center, Karadeniz Technical University, Trabzon, Turkey.
Jazyk:	angličtina
Zdroj:	The Journal of pharmacy and pharmacology [J Pharm Pharmacol] 2022 Jan 05; Vol. 74 (1), pp. 94-102.
DOI:	10.1093/jpp/rgab072
Abstrakt:	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 Ca2+ 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 Ca2+-free conditions and the CCh-induced contraction of DSM strips preincubated with nifedipine in Ca2+-containing Krebs solution. Furthermore, TMZ (1000 µM) significantly decreased the Ca2+ 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 Ca2+ 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. (© The Author(s) 2021. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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