{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T11:06:27Z","timestamp":1740135987567,"version":"3.37.3"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key \ufb01ndings<\/jats:title>\n                  <jats:p>TMZ (300 or 1000 \u00b5M) inhibited carbachol (CCh)- and KCl-induced contractions and produced a concentration-dependent (10\u20131000 \u00b5M) 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 \u00b5M) 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 \u00b5M) significantly decreased the Ca2+ levels in fura-2-loaded A7r5 cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jpp\/rgab072","type":"journal-article","created":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T15:18:22Z","timestamp":1619536702000},"page":"94-102","source":"Crossref","is-referenced-by-count":5,"title":["The inhibitory effect of trimetazidine on detrusor contractility \u2013 a potential repositioning of trimetazidine for the treatment of overactive bladder"],"prefix":"10.1093","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1982-7820","authenticated-orcid":false,"given":"Seckin","family":"Engin","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Karadeniz Technical University , Trabzon ,","place":["Turkey"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yesim","family":"Kaya Yasar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Karadeniz Technical University , Trabzon ,","place":["Turkey"]},{"name":"Drug and Pharmaceutical Technology Application and Research Center, Karadeniz Technical University , Trabzon ,","place":["Turkey"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elif Nur","family":"Barut","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Karadeniz Technical University , Trabzon ,","place":["Turkey"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Damla","family":"Getboga","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Ege University , \u0130zmir ,","place":["Turkey"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasemin","family":"Erac","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Ege University , 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