Trimetazidine is a lipophilic piperazine derivative, which is used for angina pectoris [1]. Trimetazidine acts by selectively inhibiting mitochondrial long-chain 3-ketoacyl-CoA thiolase (HADHA), and in turn, inhibits β-oxidation of fatty acids and promotes glucose utilization, improving cardiac energy metabolism[2]. Trimetazidine has been widely used in animal models to enhance the contraction and relaxation functions of the heart and to improve the recovery of cardiac dysfunction caused by ischemia-reperfusion[3].
In vitro, Trimetazidine treatment for 24h significantly inhibited the viability of PANC-1 cells, with an IC50 value of 3.98mM [4]. Treatment of MCF-7 cells with Trimetazidine (250μM) in combination with paclitaxel (1μM) for 72 hours significantly induced apoptosis and decreased ATP levels in the cells[5].
In vivo, Trimetazidine treatment via oral administration at a dose of 7.2mg/kg/day for 3 days significantly reduced the oxidative stress in the brain and liver of mice induced by lipopolysaccharide (200μg/kg)[6]. A single intraperitoneal injection of 7.2mg/kg of Trimetazidine for 24 hours significantly inhibited the acute gastric mucosal injury induced by indomethacin in rats and enhanced the gastric acid secretion response[7]. Oral administration of 20mg/kg/day for 28 days reversed the hypertension and left ventricular dysfunction caused by sunitinib in mice[8].
References:
[1] Jain S, Bharal N, Mediratta P K, et al. Trimetazidine exerts protection against increasing current electroshock seizure test in mice[J]. Seizure, 2010, 19(5): 300-302.
[2] Chrusciel P, Rysz J, Banach M. Defining the role of trimetazidine in the treatment of cardiovascular disorders: some insights on its role in heart failure and peripheral artery disease[J]. Drugs, 2014, 74(9): 971-980.
[3] Dimitrova D, Manolov S, Ivanov I, et al. Trimetazidine–Profen Hybrid Molecules: Synthesis, Chemical Characterization, and Biological Evaluation of Their Racemates[J]. Pharmaceuticals, 2025, 18(9): 1251.
[4] Şekeroğlu Z A, Şekeroğlu V, Işık S, et al. Trimetazidine alone or in combination with gemcitabine and/or abraxane decreased cell viability, migration and ATP levels and induced apoptosis of human pancreatic cells[J]. Clinics and Research in Hepatology and Gastroenterology, 2021, 45(6): 101632.
[5] Atlı Şekeroğlu Z, Kendigelen E, Şekeroğlu V, et al. Effects of trimetazidine on anticancer activity and toxicity of abraxane in MCF-7 breast cancer cells[J]. Rendiconti Lincei. Scienze Fisiche e Naturali, 2022, 33(4): 879-888.
[6] Abdel-Salam O M E, Mohammed N A, Sleem A A. The effects of trimetazidine on lipopolysaccharide-induced oxidative stress in mice[J]. EXCLI journal, 2011, 10: 162.
[7] Abdel-Salam O M E, El-Batran S. Pharmacological investigation of trimetazidine in models of inflammation, pain and gastric injury in rodents[J]. Pharmacology, 2005, 75(3): 122-132.
[8] Yang Y, Li N, Chen T, et al. Trimetazidine ameliorates sunitinib-induced cardiotoxicity in mice via the AMPK/mTOR/autophagy pathway[J]. Pharmaceutical biology, 2019, 57(1): 625-631.
Trimetazidine是一种亲脂性piperazine衍生物，用于治疗心绞痛[1]。Trimetazidine通过选择性抑制线粒体长链3-ketoacyl-CoA thiolase (HADHA)，进而抑制脂肪酸的β-氧化并促进葡萄糖利用，改善心脏能量代谢[2]。Trimetazidine已被广泛用于动物模型，以增强心脏的收缩和舒张功能，并改善缺血再灌注引起的心功能障碍的恢复[3]。
在体外，Trimetazidine处理24小时显著抑制了PANC-1细胞的活力，IC50值为3.98mM[4]。用250μM的 Trimetazidine联合1μM紫杉醇处理MCF-7细胞72小时，显著诱导了细胞凋亡并降低了细胞内的ATP水平[4]。
在体内，每日口服7.2mg/kg剂量的Trimetazidine，连续3天，显著降低了脂多糖(200μg/kg)诱导的小鼠大脑和肝脏中的氧化应激[6]。单次腹腔注射7.2mg/kg的Trimetazidine 24小时，显著抑制了indomethacin诱导的大鼠急性胃黏膜损伤，并增强了胃酸分泌反应[7]。每日口服20mg/kg的Trimetazidine，连续28天，逆转了sunitinib诱导的小鼠高血压和左心室功能障碍[8]。