Trimetazidine

Names

[ Name ]:
Trimetazidine

[Synonym ]:
Piperazine-2,2,3,3,5,5,6,6-d, 1-[(2,3,4-trimethoxyphenyl)methyl]-
Trimetazidine HCl
EINECS 225-690-2
MFCD00868263
Trimetazidine
1-(2,3,4-Trimethoxybenzyl)(2,2,3,3,5,5,6,6-H)piperazine

Biological Activity

[Description]:

Trimetazidine is a selective long chain 3-ketoyl coenzyme A thiolase inhibitor with an IC50 of 75 nM, which can inhibit β-oxidation of free fatty acid (FFA). Trimetazidine is an effective antianginal agent and a cytoprotective drug, has anti-oxidant, anti-inflammatory, antinociceptive and gastroprotective properties. Trimetazidine triggers autophagy. Trimetazidine is also a 3-hydroxyacyl-CoA dehydrogenase (HADHA) inhibitor[1][2][3][4].

[Related Catalog]:

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Autophagy >> Autophagy

[Target]

IC50: 75 nM (long chain 3-ketoyl coenzyme A thiolase)[2] β-oxidation[2] Autophagy[3] 3-hydroxyacyl-CoA dehydrogenase (HADHA)[4]

[In Vitro]

Trimetazidine (1-100 μM; 24 hours; HUVECs) could enhance the viability of the injured HUVECs induced by oxidation in a certain dose-dependent manner[1]. Cell Viability Assay[1] Cell Line: Human umbilical vein endothelial cells (HUVECs) Concentration: 1 μM,10 μM,100 μM Incubation Time: 24 hours Result: Enhanced the viability of the injured HUVECs induced by oxidation.

[In Vivo]

Trimetazidine (5-20 mg/kg; oral administration; 1 hour; Swiss albino male mice) in 10 and 20mg/kg doses significantly raises the seizure-threshold current in the ICES test in the mice[5]. Animal Model: Swiss albino male mice (24-35 g)[4] Dosage: 5 mg/kg, 10 mg/kg and 20 mg/kg; 10 mL/kg body weight Administration: Oral administration ; 1 hour Result: In 10 and 20mg/kg doses significantly raised the seizure-threshold current in the ICES test.

[References]

[1]. Shenghu He, et al. Protective effects of trimetazidine against vascular endothelial cell injury induced by oxidation. Journal of Geriatric Cardiology, December 2008 , Vol 5 No 4.

[2]. Chrusciel P, et al. Defining the role of trimetazidine in the treatment of cardiovascular disorders: some insights on its role in heart failure and peripheral artery disease. Drugs. 2014 Jun;74(9):971-80.

[3]. Kantor PF, et al. The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res. 2000 Mar 17;86(5):580-8.

[4]. Hossain F, et al.Inhibition of Fatty Acid Oxidation Modulates Immunosuppressive Functions of Myeloid-Derived Suppressor Cells and Enhances Cancer Therapies. Cancer Immunol Res. 2015 Nov;3(11):1236-47.

[5]. Jain S, et al. Trimetazidine exerts protection against increasing current electroshock seizure test in mice. Seizure. 2010 Jun;19(5):300-2.

Chemical & Physical Properties

[ Density]:
1.1±0.1 g/cm3

[ Boiling Point ]:
364.0±37.0 °C at 760 mmHg

[ Melting Point ]:
200 - 205ºC

[ Molecular Formula ]:
C₁₄H₂₂N₂O₃

[ Molecular Weight ]:
274.385

[ Flash Point ]:
174.0±26.5 °C

[ Exact Mass ]:
274.213257

[ PSA ]:
42.96000

[ LogP ]:
0.80

[ Vapour Pressure ]:
0.0±0.8 mmHg at 25°C

[ Index of Refraction ]:
1.524

Safety Information

[ Hazard Codes ]:
Xi

[ HS Code ]:
2933599090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2933599090

[ Summary ]:
2933599090. other compounds containing a pyrimidine ring (whether or not hydrogenated) or piperazine ring in the structure. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%