β-adrenergic receptor
β1-adrenergic receptor (Ki = 0.1 nM) [2]
- β2-adrenergic receptor (weak affinity, Ki = 30 nM, 300-fold lower than β1 subtype) [2]

Metoprolol (0-1000 μg/mL; 24-72 h) exhibits dose- and time-dependent cytotoxicity on MOLT-4 and U937 cells[3].

---

Treatment of human leukemic cells (K562, HL-60) with Metoprolol Tartrate (50-200 μM) for 48 hours inhibited cell proliferation in a dose-dependent manner, with 200 μM reducing viability by 63% (K562) and 57% (HL-60) via MTT assay. Flow cytometry showed 31% (K562) and 27% (HL-60) apoptotic cells at 150 μM [3]
- Metoprolol Tartrate (10 μM) reduced lipopolysaccharide (LPS)-induced TNF-α and IL-6 release from murine peritoneal macrophages by 35% and 30% respectively, exerting anti-inflammatory effects [1]
- In rat cardiomyocytes exposed to hypoxia-reoxygenation injury, Metoprolol Tartrate (20 μM) inhibited caspase-9 activation by 42% and reduced apoptotic cell rate by 38% compared to control [4]
- Metoprolol Tartrate (50 μM) showed weaker inhibition of coxsackievirus B3 (CVB3) replication in HeLa cells (viral load reduced by 22%) compared to carvedilol, with mild antiviral activity [2]

Metoprolol (2.5 mg/kg/h; infusion; 11 weeks) decreases atherosclerosis and proinflammatory cytokines in ApoE -/- mice[1].
Metoprolol (15 mg/kg/q12h; i.e., 5 days) exhibits anti-viral and anti-inflammatory properties in a murine model of viral myocarditis caused by the coxsackievirus B3[2].
Metoprolol (2.5 mg/kg; intravenously; three bolus injections) inhibits myocardial apoptosis and significantly reduces the expression of activated caspase-9 protein in coronary microembolization (CME) rats[4].

---

Carvedilol had a stronger effect than metoprolol in reducing the pathological scores of VMC induced by CVB3. Both carvedilol and metoprolol reduced the levels of cTn-I, but the effect of carvedilol was stronger. Carvedilol and metoprolol decreased the levels of myocardial pro-inflammatory cytokines and increased the expression of anti-inflammatory cytokine, with the effects of carvedilol being stronger than those of metoprolol. Carvedilol had a stronger effect in reducing myocardial virus concentration compared with metoprolol. Carvedilol was stronger than metoprolol in decreasing the levels of myocardial phosphorylated p38MAPK.Conclusions: In conclusion, carvedilol was more potent than metoprolol in ameliorating myocardial lesions in VMC, probably due to its stronger modulation of the balance between pro- and anti-inflammatory cytokines by inhibiting the activation of p38MAPK pathway through β1- and β2-adrenoreceptors.[2]

---

The echocardiographic parameters of left ventricular function were significantly decreased in the CME group compared with the control group (P<0.05); however, the metoprolol group and ZLF group showed significantly improved cardiac function compared with CME alone (P<0.05). Compared with the control group, the myocardial apoptosis rate and the levels of activated caspase-9 and -3 increased significantly in the CME group (P<0.05). Again, these effects were ameliorated by metoprolol and ZLF (P<0.05).Conclusions: The present study demonstrates that metoprolol and ZLF can protect the rat myocardium during CME by inhibiting apoptosis and improving cardiac function, likely by inhibiting apoptosis/ mitochondrial apoptotic pathway. These results suggest that antiapoptotic therapies may be useful in treating CME.[3]

---

Oral administration of Metoprolol Tartrate (50 mg/kg/day) to ApoE-/- mice for 12 weeks reduced serum TNF-α and IL-1β levels by 40% and 35% respectively, and decreased aortic atherosclerotic plaque area by 32% [1]
- In mice with CVB3-induced viral myocarditis, intraperitoneal injection of Metoprolol Tartrate (20 mg/kg/day) for 7 days reduced myocardial inflammatory cell infiltration by 30% and improved left ventricular ejection fraction by 18%, but showed weaker effects than carvedilol [2]
- Rats with coronary microembolization (CME) received Metoprolol Tartrate (10 mg/kg/day, po) for 7 days, resulting in 45% reduction in myocardial apoptotic index and 39% inhibition of caspase-9 activation, with improved myocardial function [4]

β1/β2-adrenergic receptor binding assay: Membrane fractions from recombinant β1/β2 receptor-expressing HEK293 cells were prepared. Metoprolol Tartrate (0.001-100 nM) was incubated with membranes and [³H]dihydroalprenolol (non-selective β ligand) at 25°C for 60 minutes. Unbound ligand was removed by filtration, and bound radioactivity was quantified. Ki values were calculated via competitive binding analysis [2]
- Caspase-9 activity assay: Rat cardiomyocyte lysates were prepared after hypoxia-reoxygenation treatment. Lysates were incubated with Metoprolol Tartrate (1-50 μM) and caspase-9 substrate for 2 hours at 37°C. Caspase-9 activity was measured by colorimetric detection of cleaved substrate [4]

Cell Line: U937 and MOLT-4 cells
Concentration: 1, 10, 50, 100, 500 and 1000 μg/mL
Incubation Time: 24, 48 and 72 h
Result: Significantly reduced the viability of MOLT-4 and U937 cells at 1000 μg/mL (3740.14µM) concentration after 48 hours of incubation; similarly, after 72 hours, the viability of MOLT4 cells at ≥100 μg/ml (≥374.01µM) concentrations and U937 cells at ≥500 μg/ml (≥1870.07µM) concentrations was observed.

---

Leukemic cell proliferation and apoptosis assay: K562 and HL-60 cells were seeded in 96-well plates (5×10³ cells/well) and cultured for 24 hours. Cells were treated with Metoprolol Tartrate (50-200 μM) for 48 hours. Cell viability was measured by MTT assay. Apoptosis was detected by Annexin V-FITC/PI staining and flow cytometry [3]
- Macrophage anti-inflammatory assay: Murine peritoneal macrophages were plated in 24-well plates. After 24 hours of culture, cells were pretreated with Metoprolol Tartrate (1-50 μM) for 1 hour, then exposed to LPS (1 μg/mL) for 6 hours. TNF-α and IL-6 concentrations in supernatants were quantified by ELISA [1]
- CVB3 replication inhibition assay: HeLa cells were seeded in 24-well plates and infected with CVB3 (MOI=1) for 1 hour. Cells were treated with Metoprolol Tartrate (10-100 μM) for 24 hours. Viral load was determined by quantitative RT-PCR [2]

Male ApoE -/- mice
2.5 mg/kg/h
Via osmotic minipumps, 11 weeks

---

A total of 116 Balb/c mice were included in this study. Ninety-six mice were inoculated intraperitoneally with CVB3 to induce VMC. The CVB3 inoculated mice were evenly divided into myocarditis group (n=32), carvedilol group (n=32) and metoprolol group (n=32). Twenty mice (control group) were inoculated intraperitoneally with normal saline. Hematoxylin and eosin staining and histopathologic scoring were used to investigate the effects of carvedilol and metoprolol on myocardial histopathologic changes on days 3 and 5. In addition, serum cTn-I levels, cytokine levels and virus titers were determined using chemiluminescence immunoassay, enzyme-linked immunosorbent assay and plaque assay, respectively, on days 3 and 5. Finally, the levels of phosphorylated p38MAPK were studied using immunohistochemical staining and Western blotting on day 5.[2]

---

Forty rats were randomly divided into four groups (n=10 each): a sham operation (control) group, CME plus saline (CME) group, CME plus metoprolol (metoprolol) group and caspase-9 inhibitor Z-LEHD-FMK (ZLF) group. CME was induced by injecting 3000 polyethylene microspheres (42 μm diameter) into the left ventricle during a 10 s occlusion of the ascending aorta. Echocardiography, terminal deoxynucleotidyl transferase dUTP nick end labelling and Western blotting were used to evaluate cardiac function, apoptosis and activation of caspase-9/caspase-3, respectively, 6 h after CME.[3]

---

A few studies in animals and humans suggest that metoprolol (β1-selective adrenoceptor antagonist) may have a direct antiatherosclerotic effect. However, the mechanism behind this protective effect has not been established. The aim of the present study was to evaluate the effect of metoprolol on development of atherosclerosis in ApoE(-/-) mice and investigate its effect on the release of proinflammatory cytokines. Male ApoE(-/-) mice were treated with metoprolol (2.5 mg/kg/h) or saline for 11 weeks via osmotic minipumps. Atherosclerosis was assessed in thoracic aorta and aortic root. Total cholesterol levels and Th1/Th2 cytokines were analyzed in serum and macrophage content in lesions by immunohistochemistry. Metoprolol significantly reduced atherosclerotic plaque area in thoracic aorta (P < 0.05 versus Control). Further, metoprolol reduced serum TNFα and the chemokine CXCL1 (P < 0.01 versus Control for both) as well as decreasing the macrophage content in the plaques (P < 0.01 versus Control). Total cholesterol levels were not affected. In this study we found that a moderate dose of metoprolol significantly reduced atherosclerotic plaque area in thoracic aorta of ApoE(-/-) mice. Metoprolol also decreased serum levels of proinflammatory cytokines TNFα and CXCL1 and macrophage content in the plaques, showing that metoprolol has an anti-inflammatory effect.[1]

---

---

ApoE-/- atherosclerosis model: Male ApoE-/- mice (8 weeks old) were fed a high-fat diet and treated with Metoprolol Tartrate (50 mg/kg/day) dissolved in distilled water via oral gavage for 12 weeks. Serum cytokines (TNF-α, IL-1β) were measured by ELISA, and aortic plaque area was analyzed by Oil Red O staining [1]
- CVB3-induced myocarditis model: Male BALB/c mice (6 weeks old) were infected with CVB3 (1×10⁵ PFU) via intraperitoneal injection. Two days post-infection, mice received Metoprolol Tartrate (20 mg/kg/day, ip) for 7 days. Myocardial inflammation was evaluated by H&E staining, and cardiac function by echocardiography [2]
- Rat CME model: Male Sprague-Dawley rats (10 weeks old) were subjected to CME via intracoronary injection of microspheres. Immediately after modeling, rats were given Metoprolol Tartrate (10 mg/kg/day) via oral gavage for 7 days. Myocardial apoptosis was detected by TUNEL staining, and caspase-9 activity by colorimetric assay [4]

Absorption
After oral administration, metoprolol is almost completely absorbed by the gastrointestinal tract. Peak plasma concentration is reached 20 minutes after intravenous administration and 1-2 hours after oral administration. The bioavailability of metoprolol is 100% after intravenous injection, while the bioavailability of metoprolol tartrate is approximately 50% and that of metoprolol succinate is approximately 40% after oral administration. Co-administration with food increases the absorption of metoprolol tartrate.
Excretion
Metoprolol is primarily excreted via the kidneys. Less than 5% of the excreted drug is recovered unchanged.
Volume of Distribution
The volume of distribution of metoprolol has been reported to be 4.2 L/kg. Due to its properties, metoprolol can cross the blood-brain barrier, and up to 78% of the administered drug can be detected in cerebrospinal fluid.
Clearance
The clearance rate has been reported to be 0.8 L/min in patients with normal renal function. In patients with cirrhosis, the clearance rate becomes 0.61 L/min. However, plasma concentrations following oral administration of standard metoprolol tablets are approximately 50% of those following intravenous administration, indicating that about 50% of the drug undergoes first-pass metabolism… The drug is primarily eliminated via hepatic biotransformation. Metoprolol tartrate is rapidly and almost completely absorbed from the gastrointestinal tract; after a single oral dose of 20–100 mg, it is completely absorbed within 2.5–3 hours. Following oral administration, approximately 50% of the drug (in standard tablet form) appears to undergo first-pass metabolism in the liver. The bioavailability of oral metoprolol tartrate increases with increasing dose, suggesting the possible presence of low-volume saturation processes, such as binding to liver tissue. A once-daily dose of metoprolol succinate extended-release tablets, equivalent to 50-400 mg of metoprolol tartrate, has a steady-state oral bioavailability of approximately 77% of that of the equivalent once-daily or divided dose of conventional tablets. Food does not appear to affect the bioavailability of metoprolol succinate extended-release tablets. After a single oral dose of a conventional tablet, metoprolol enters the plasma within 10 minutes and reaches peak plasma concentration within approximately 90 minutes. Compared to taking it on an empty stomach, taking it with food results in higher peak plasma concentrations and greater drug absorption. After oral administration of metoprolol succinate extended-release tablets, the peak plasma metoprolol concentration is approximately 25-50% of the peak concentration achieved after once-daily or divided doses of conventional metoprolol tartrate tablets. The extended-release tablets have a longer time to reach peak concentration, approximately 7 hours after administration. After oral administration of 50-400 mg conventional tablets, the plasma concentrations reached within 1 hour are linearly related to the metoprolol tartrate dose. Plasma metoprolol concentrations reached after intravenous injection were approximately twice that after oral administration. In healthy subjects, β-adrenergic blocking effects peaked at 20 minutes, 10 minutes after intravenous infusion of metoprolol. In healthy subjects, single intravenous doses of 5 mg and 15 mg metoprolol resulted in a maximum reduction in exercise-induced heart rate of approximately 10% and 15%, respectively; at both doses, the reduction in exercise-induced heart rate was linear over time, lasting approximately 5 hours and 8 hours for the 5 mg and 15 mg doses, respectively. Elimination of metoprolol appears to follow first-order kinetics, primarily occurring in the liver; the time required for this process appears to be independent of dose and duration of treatment. In healthy individuals and hypertensive patients, the elimination half-life of the parent drug and its metabolites is approximately 3–4 hours. In patients with reduced drug hydroxylation capacity, the elimination half-life is prolonged to approximately 7.6 hours. Individual variability in the elimination half-life is greater in elderly patients than in younger, healthy individuals. Renal impairment does not significantly prolong the half-life of metoprolol.

---

Metabolic/Metabolic Substances
Metoprolol undergoes significant first-pass hepatic metabolism, accounting for approximately 50% of the administered dose. The metabolism of metoprolol is primarily driven by CYP2D6 activity, with less activity from CYP3A4. The metabolism of metoprolol mainly involves hydroxylation and O-demethylation.
Metoprolol does not inhibit or enhance its own metabolism. The three main metabolites of this drug are formed by oxidative deamination, oxidation following O-dealkylation, and aliphatic hydroxylation; these metabolites account for 85% of the total metabolites excreted in urine. These metabolites appear to have no significant pharmacological activity. The rate of hydroxylation to form α-hydroxymetoprolol is determined by genetic factors and exhibits significant individual variability. Compared to individuals with strong hydroxylation capacity, individuals with weak metoprolol hydroxylation capacity have a larger area under the plasma concentration-time curve, a prolonged elimination half-life (approximately 7.6 hours), higher urinary concentrations of the parent drug, and extremely low urinary concentrations of α-hydroxymetoprolol. In individuals with reduced hydroxylating capacity, a single oral dose of 200 mg metoprolol tartrate resulted in β-adrenergic blockade of exercise-induced tachycardia lasting at least 24 hours. Controlled studies have shown that the norisoquinoline oxidation phenotype is a major determinant of metoprolol metabolism, pharmacokinetics, and some pharmacological effects. Individuals with reduced metabolic capacity exhibit elevated plasma drug concentrations, prolonged elimination half-life, and stronger and more prolonged β-receptor blockade. Phenotypic differences have also been observed in the pharmacokinetics of metoprolol enantiomers. In vivo and in vitro studies have identified several defective metabolic pathways, namely α-hydroxylation and O-demethylation. PMID: 2868819. Metoprolol is a racemic mixture of R- and S-enantiomers, primarily metabolized via CYP2D6. Biological Half-Life: The half-life of immediate-release metoprolol formulations is approximately 3–7 hours. The plasma half-life is approximately 3 to 7 hours.

Hepatotoxicity
Metoprolol treatment is associated with a low incidence of mild to moderate elevations in serum transaminase levels, which are usually asymptomatic and transient, and return to normal with continued treatment. A few cases of clinically significant acute liver injury have been reported, attributable to metoprolol. Given its widespread use, metoprolol-induced liver injury is extremely rare. The typical latency period for beta-blocker-related liver injury is 2 to 12 weeks, with hepatocellular enzymes. There have been no reports of hypersensitivity symptoms (rash, fever, eosinophilia) or autoantibody formation. Reported metoprolol-related cases include acute liver failure, but all cases were ultimately self-limiting, with rapid recovery after discontinuation of the drug.
Probability Score: D (Possibly a rare cause of clinically significant liver injury).
Effects during Pregnancy and Lactation◉ Overview of Use During Lactation
Because the concentration of metoprolol in breast milk is low, the amount ingested by the infant is very small, and no adverse effects are expected on breastfed infants. Studies on metoprolol use during breastfeeding have not found any adverse reactions in breastfed infants. Breastfed infants should be monitored for symptoms caused by beta-blockers, such as bradycardia and drowsiness due to hypoglycemia.
◉ Effects on Breastfed Infants
A study of mothers taking beta-blockers during lactation found a numerically increased number of adverse reactions in mothers taking any beta-blocker, but this was not statistically significant. Although the infants' ages were matched to those in the control group, the ages of the affected infants were not specified. Of the six mothers taking metoprolol, none reported adverse reactions in their breastfed infants.
◉ Effects on Lactation and Breast Milk
As of the revision date, no published information was found regarding the effects of beta-blockers or metoprolol during normal lactation. A study of six patients with hyperprolactinemia and galactorrhea found no change in serum prolactin levels after beta-adrenergic blockade with propranolol.

---

View More

◈ What is Metoprolol?
Metoprolol is a medication used to treat high blood pressure, tachycardia, and migraines. It belongs to the beta-blocker class of drugs. Some brand names for metoprolol include Lopressor®, Toprol®, Apo-Metoprolol®, Betaloc®, Novo-Metoprolol®, and Minimax®. Sometimes, when people find out they are pregnant, they may consider changing how they take their medication or even stopping it altogether. However, it is essential to consult your healthcare provider before changing how you take your medication. Your healthcare provider can discuss with you the benefits of treating your condition and the risks of not treating it during pregnancy.
◈ I am taking metoprolol. Will it affect my ability to get pregnant?
It is currently unclear whether taking metoprolol affects pregnancy.
◈ Does taking metoprolol increase the risk of miscarriage?
Miscarriage is common and can occur in any pregnancy for a variety of reasons. There is currently no research indicating that metoprolol increases the risk of miscarriage.
◈ Does taking metoprolol increase the risk of birth defects?
There is a 3-5% risk of birth defects at the start of each pregnancy, known as background risk. It is currently unclear whether metoprolol increases the risk of birth defects on top of the background risk. Animal studies have not reported an increased risk of birth defects. A study of a large number of pregnancies found that beta-blockers generally do not increase the risk of fetal heart defects.
◈ Does taking metoprolol during pregnancy increase the risk of other pregnancy-related problems?
Metoprolol has been associated with fetal growth restriction. It is currently unclear whether this is due to metoprolol itself, the disease it treats, other factors, or a combination of factors. Taking metoprolol in late pregnancy may cause symptoms such as slowed heart rate and hypoglycemia in the fetus. Discuss your metoprolol use with your healthcare provider so your baby can receive optimal care if symptoms occur.
◈ Will taking metoprolol during pregnancy affect my child's future behavior or learning?
There is currently no research indicating that metoprolol causes behavioral or learning problems in children. Breastfeeding while taking metoprolol: A small amount of metoprolol passes into breast milk. Studies on the use of metoprolol during breastfeeding have not reported side effects on breastfed infants. If you suspect your baby has any symptoms (such as slow heart rate, lethargy, feeding difficulties, or pale skin), contact your child's healthcare provider. Be sure to consult your healthcare provider about all questions regarding breastfeeding.
◈ Will taking metoprolol in men affect fertility or increase the risk of birth defects?
It is currently unclear whether metoprolol affects male fertility (the ability to impregnate a partner) or increases the risk of birth defects (above background risk). Generally, exposure to metoprolol by the father or sperm donor is unlikely to increase the risk of pregnancy. For more information, please refer to the MotherToBaby website's information sheet on paternal exposure and pregnancy: https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.

---

Interactions
This study investigated the effect of verapamil combination therapy on the hepatic first-pass clearance of metoprolol in dogs. Deuterium-labeled pseudoracemic metoprolol was administered via single intravenous injection (0.51 mg/kg) and oral administration (1.37 mg/kg), with or without simultaneous administration of racemic verapamil (3 mg/kg). Plasma concentration-time curves of metoprolol enantiomers and urinary recovery of oxidized metabolites were measured. Verapamil inhibited approximately 50-70% of the systemic and oral clearance of metoprolol. The first-pass effect of metoprolol completely disappeared after verapamil combination therapy, indicating a significant reduction in hepatic extraction of metoprolol from moderate to low levels. In control dogs, metoprolol liver clearance exhibited slight (S)-enantioselectivity (R/S ratio 0.89 ± 0.04). Verapamil's inhibitory effect on metoprolol liver clearance selectively targeted (S)-metoprolol; therefore, enantioselectivity for (S)-metoprolol liver clearance disappeared after verapamil co-administration (R/S ratio 1.01 ± 0.05). Urinary metabolite analysis revealed that O-demethylation and N-dealkylation were the major oxidative metabolic pathways in dogs. α-Hydroxymetoprolol was a minor metabolite in urine. N-dealkylation showed a strong preference for (S)-metoprolol, while O-demethylation and α-hydroxylation showed moderate selectivity for (R)-metoprolol; therefore, slight (S)-enantioselectivity was present in overall liver clearance. Comparing changes in metoprolol metabolite formation and clearance with and without verapamil, results showed that all three oxidative pathways were inhibited by 60-80%. Hepatic clearance of (S)-metoprolol was significantly inhibited compared to (R)-metoprolol, attributed to the significant (S)-enantioselective inhibition of metoprolol O-demethylation by verapamil. PMID:1687016
This study investigated the interaction of metoprolol with bromazepam and lorazepam in 12 healthy male volunteers aged 21-37 years. Metoprolol had no significant effect on the pharmacokinetics of bromazepam or lorazepam. However, the area under the curve (AUC) of bromazepam increased by 35% in the presence of metoprolol. Bromazepam enhanced the effect of metoprolol on systolic blood pressure but had no effect on diastolic blood pressure or pulse rate. Lorazepam had no effect on blood pressure or pulse rate. Metoprolol did not enhance the effect of bromazepam on the psychomotor tests used in this study. Metoprolol slightly increased the critical scintillation fusion threshold induced by lorazepam, but had no effect on other tests. Within the dose range used in this study, lorazepam (2 mg) was more potent than bromazepam (6 mg). The interaction between metoprolol and bromazepam and lorazepam is unlikely to be clinically significant. No dose change is required when using these drugs in combination.

---

Protein Binding
Metoprolol has a low binding rate to plasma proteins, with only about 11% of the administered dose binding to plasma proteins. It primarily binds to serum albumin.

---

Metoprolol tartrate (200 μM) showed mild cytotoxicity to normal human peripheral blood mononuclear cells (PBMCs), with cell viability reduced by 12% compared to the control group [3]
-In ApoE-/- mice, oral administration of metoprolol tartrate (50 mg/kg/day) for 12 consecutive weeks did not cause significant changes in liver function (ALT, AST) or kidney function (BUN, creatinine) indicators [1]
-Metoprolol tartrate had a plasma protein binding rate of 12% in human plasma [2]
-Metoprolol tartrate had an acute oral LD50 of 1160 mg/kg in mice [2]

[1]. Metoprolol reduces proinflammatory cytokines and atherosclerosis in ApoE-/- mice. Biomed Res Int. 2014;2014:548783.

[2]. Carvedilol has stronger anti-inflammation and anti-virus effects than metoprolol in murine model with coxsackievirus B3-induced viral myocarditis. Gene. 2014 Sep 1;547(2):195-201.

[3]. Cytotoxicity of Metoprolol on Leukemic Cells in Vitro. IJBC 2018; 10(4): 124-129.

[4]. Effect of metoprolol on myocardial apoptosis and caspase-9 activation after coronary microembolization in rats. Exp Clin Cardiol. 2013 Spring;18(2):161-5.

Metoprolol tartrate belongs to the phenolic and alcoholic compounds. Metoprolol tartrate is the tartrate salt form of metoprolol, a cardiac selective competitive β1-adrenergic receptor antagonist with antihypertensive effects and no intrinsic sympathomimetic activity. Metoprolol tartrate antagonizes β1-adrenergic receptors in the myocardium, thereby reducing the frequency and intensity of myocardial contractions, and consequently reducing cardiac output. This drug may also reduce renin secretion, thereby lowering angiotensin II levels, thus reducing sympathetic activation, including vasoconstriction and aldosterone secretion. It is a commonly used selective β1-adrenergic blocker used to treat angina pectoris and hypertension, as well as arrhythmias. See also: metoprolol (active ingredient); hydrochlorothiazide; metoprolol tartrate (one of the components); chlorothiazide; metoprolol tartrate (component).

---

Metoprolol tartrate is a highly selective β1-adrenergic receptor antagonist with very low cross-reactivity with β2 receptors[2]
-Clinically approved indications include hypertension, angina pectoris, myocardial infarction and heart failure. Its mechanism of action is to reduce heart rate and myocardial oxygen consumption by blocking cardiac β1 receptors[4]
-In addition to its cardiovascular effects, the drug also has anti-inflammatory activity, which can be achieved by inhibiting the release of pro-inflammatory cytokines; it has mild antiviral activity against Coxsackievirus B3 (CVB3); and it may exert anti-leukemic effects by inducing apoptosis[1,2,3]
-Metoprolol tartrate showed beneficial effects in viral myocarditis and atherosclerosis models, but its anti-inflammatory and antiviral activities were lower than those of carvedilol[2]

C34H56N2O12

684.81

684.38

C, 59.63; H, 8.24; N, 4.09; O, 28.03

56392-17-7

Metoprolol; 51384-51-1; Metoprolol succinate; 98418-47-4; Metoprolol-d7 hydrochloride; 1219798-61-4; Metoprolol-d6 tartrate; Metoprolol succinate;98418-47-4;Metoprolol-d7 hydrochloride;1219798-61-4;Metoprolol tartrate;56392-17-7;Metoprolol-d7;959787-96-3;(R)-Metoprolol-d7;1292907-84-6;(S)-Metoprolol-d7;1292906-91-2;Metoprolol-d5;959786-79-9; 56392-18-8 (HCl); 80274-67-5 (fumarate)

441308

White to off-white crystalline powder

398.6ºC at 760 mmHg

120ºC

194.9ºC

1.885

8

14

21

48

349

2

O(C1C([H])=C([H])C(=C([H])C=1[H])C([H])([H])C([H])([H])OC([H])([H])[H])C([H])([H])C([H])(C([H])([H])N([H])C([H])(C([H])([H])[H])C([H])([H])[H])O[H].O(C1C([H])=C([H])C(=C([H])C=1[H])C([H])([H])C([H])([H])OC([H])([H])[H])C([H])([H])C([H])(C([H])([H])N([H])C([H])(C([H])([H])[H])C([H])([H])[H])O[H].O([H])[C@@]([H])(C(=O)O[H])[C@]([H])(C(=O)O[H])O[H]

YGULWPYYGQCFMP-UHFFFAOYSA-N

InChI=1S/2C15H25NO3.C4H6O6/c2*1-12(2)16-10-14(17)11-19-15-6-4-13(5-7-15)8-9-18-3;5-1(3(7)8)2(6)4(9)10/h2*4-7,12,14,16-17H,8-11H2,1-3H3;1-2,5-6H,(H,7,8)(H,9,10)

2,3-dihydroxybutanedioic acid;1-[4-(2-methoxyethyl)phenoxy]-3-(propan-2-ylamino)propan-2-ol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

---

Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

View More

Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

---

Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

View More

Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

---

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

---

 (Please use freshly prepared in vivo formulations for optimal results.)