| Description | Norepinephrine is an alkaloid neurotransmitter and an effective adrenergic receptor (AR) agonist that activates α1, α2, and β1 receptors. It is commonly used as a vasoactive agent for the treatment of shock and can also be used to induce cardiomyopathy models. |
| Targets & IC50 | β1-adrenoceptor:740 nM (Ki), α1-adrenoceptor:330 nM (Ki), α2A-adrenoceptor:56 nM (Ki) |
| In vitro | METHODS: Adult hippocampal cells were treated with Norepinephrine (0.1-10 µM) for 10-13 days and the number of neurospheres was determined using classical neurosphere assay. RESULTS: A significant increase in the number of neurospheres was obtained at 100 nm and in the presence of 1 µM Norepinephrine, and a twofold increase in the number of neurospheres was observed in the presence of 10 µM Norepinephrine. [1] METHODS: Human pancreatic cancer cells BxPC-3 and Panc-1 were treated with Norepinephrine (10 µM) for 12-48 h. Cell viability was assayed by MTT Assay. RESULTS: Norepinephrine treatment alone significantly enhanced the viability of PDAC cells. [2] |
| In vivo | METHODS: To test in vivo activity, Norepinephrine (0.2-2 mg/kga) was administered intraperitoneally to C57BL6/J mice fed a high-fat diet once daily for two weeks. RESULTS: A subset of Norepinephrine-treated mice developed unexpected adverse events, including bladder dilatation and decreased renal perfusion due to renal discoloration. [3] |
| Synonyms | Nor-Epirenan, L-Noradrenaline, Levophed, Levonoradrenaline, Levonor, Arterenol, Aktamin |
| Disease Modeling Protocol | Sepsis-associated cardiomyopathy model- Modeling Mechanism:
Norepinephrine (NE) and lipopolysaccharide (LPS) work synergistically to induce cardiomyopathy through SIRT3/HO-1 axis-mediated ferroptosis: ① NE alone has no significant cardiotoxicity, but it can exacerbate LPS-induced oxidative stress, increasing reactive oxygen species (ROS) and lipid peroxidation levels (4-HNE and MDA are elevated); ② It inhibits SIRT3 activity, relieves its inhibition of p300, promotes HO-1 acetylation and enhances stability, accelerates heme degradation and releases ferrous ions, and induces iron overload; ③ Iron overload and lipid peroxidation together induce cardiomyocyte ferroptosis, accompanied by myocardial hypertrophy and fibrosis, ultimately leading to heart failure. - Related Products:
Norepinephrine (T7044) - Modeling Method:
Experimental Subject: Mice, C57BL/6, 8–12 weeks old, Body weight 25–28 g Dosage and Administration Route: ① Core modelling (two-hit protocol): - First challenge: IntraperitoNorepinephrineal (i.p.) injection of LPS at 5 mg/kg, single dose; - Second challenge: SimultaNorepinephrineous LPS administration with subcutaNorepinephrineous implantation of osmotic pump; Norepinephrine at 2 µg/kg/min via continuous infusion for 9 days; ② Control treatment: - LPS-only group: intraperitoNorepinephrineal injection of 5 mg/kg LPS+osmotic pump infusion of physiological saliNorepinephrine; - Norepinephrine-only group: IntraperitoNorepinephrineal injection of physiological saliNorepinephrine+osmotic pump infusion of 2 µg/kg/min Norepinephrine; - Blank control: IntraperitoNorepinephrineal injection of saliNorepinephrine+osmotic pump infusion of saliNorepinephrine; ③ Intervention validation group (optional): - Ferroptosis inhibitor: Ferrostatin-1 (Fer-1), 2 mg/kg/day, intraperitoNorepinephrineal injection, administered concurrently with modelling; - SIRT3 activator: 2-APQC, 30 mg/kg, intraperitoNorepinephrineal injection, administered continuously throughout modelling period Dosing Frequency and Duration Model: First strike: single-dose administration; Secondary challenge: Continuous infusion for 9 days - Validation:
1. Pathological Indicators: - Myocardial Injury: HE staining showed cardiomyocyte hypertrophy (cross-sectional area increased by more than 250), and Masson staining showed an increased proportion of interstitial fibrosis area (p<0.01); - Ferroplasmosis Characteristics: Transmission electron microscopy showed mitochondrial shrinkage, DHE staining showed increased ROS levels (fluorescence intensity more than 3 times that of the control group), and significantly increased ferrous ion content in tissues (OD value ≥0.4, p<0.001); 2. Molecular Indicators: - Ferroplasmosis Pathway: Western blot showed upregulated expression of HO-1 and 4-HNorepinephrine proteins and downregulated expression of SIRT3 (p<0.01); - Myocardial Markers: Serum troponin T (cTnT) and creatiNorepinephrine kinase isoenzyme (CK-MB) levels were significantly increased (p<0.001); 3. Functional Indicators: - Cardiac Function: Echocardiography showed that the left ventricular ejection fraction (EF%) decreased to below 60% (control group ≥80%, p<0.01); Survival status: The 9-day survival rate after modeling was more than 30% lower than that of the LPS group aloNorepinephrine (p<0.05).
*Precautions: *References:Ma D,et,al. Norepinephrine exacerbates LPS-induced cardiomyopathy via SIRT3/HO-1 axis-mediated ferroptosis. Crit Care. 2025 Aug 13;29(1):354. |