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| 10mg |
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| 25mg |
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| 50mg |
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Purity: ≥98%
Formoterol Hemifumarate (CGP-25827A, NSC-299587, YM-08316; Eformoterol; Aformoterol; Atock; Foradil Aerolizer), the Hemifumarate salt of formoterol, is a selective and long-acting β2-adrenoceptor agonist with airway smooth muscle relaxing effects. It has been used in the management of asthma and chronic obstructive pulmonary disease (COPD with high efficacy, and very high affinity and selectivity for the beta 2-adrenoceptor.
| Targets |
β2-adrenergic receptor
β2-adrenoceptor (agonist, Ki = 0.12 nM) [3] β1-adrenoceptor (agonist, Ki = 45 nM) [3] |
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| ln Vitro |
In vitro activity: Formoterol is a strong beta 2-adrenoceptor-specific smooth muscle relaxant with excellent efficacy, affinity, and selectivity. Given that formoterol's relaxant effect on human airway smooth muscle is resistant to repeated washing and that formoterol exhibits a "reassertion" of relaxation following washout of a beta-adrenoceptor antagonist, it appears to be retained in airway smooth muscle for extended periods of time. In test systems used in experiments, formoterol has been shown to potently inhibit these cells and processes. [1] Similar to salbutamol and salmeterol, formoterol relaxes human bronchus and guinea pig trachea preparations in isolation and inhibits the release of mediators induced by antigens from human lung fragments in a concentration-dependent manner. [2]
Formoterol Hemifumarate induced concentration-dependent relaxation of histamine-precontracted guinea pig isolated tracheal smooth muscle. At 0.01-10 nM, it achieved maximal relaxation of ~92% with an EC50 of 0.15 nM, mediated via β2-adrenoceptor activation [2] It stimulated cAMP accumulation in human bronchial smooth muscle cells. Treatment with 0.1-10 nM for 15 minutes increased intracellular cAMP levels by ~2.8-fold at 1 nM, promoting smooth muscle relaxation [1] In radioligand binding assays, it exhibited high selectivity for β2-adrenoceptors (β2/β1 selectivity ratio ~375) by displacing [3H]-dihydroalprenolol with higher affinity for β2 subtypes [3] |
| ln Vivo |
Formoterol inhibits histamine-induced bronchoconstriction in a dose-dependent manner conscious guinea-pigs.[2] In guinea pig lung, formoterol inhibits histamine-induced plasma protein extravasation (PPE), with notable inhibition seen at 10 mg/mL and 100 mg/mL. For 2-4 hours, formoterol (100 mg/mL) inhibits PPE in guinea pig lung, which is an intermediate duration of action between the previously observed durations for salbutamol (1 hour) and salmeterol (> 6 hours). In the lung of guinea pigs, formoterol prevents neutrophil accumulation (lipopolysaccharide-induced), but only at doses higher than those needed to prevent granulocyte-independent PPE (histamine-induced). In guinea pig lung, formoterol (100 mg/mL) prevents eosinophil accumulation brought on by PAF.[3]
In anesthetized guinea pigs with ovalbumin-induced allergic bronchospasm, aerosol administration of Formoterol Hemifumarate (0.1-1 μg/kg) dose-dependently reduced airway resistance by ~35-65% and increased dynamic lung compliance by ~25-40%, with effects lasting for ~12 hours [1] In conscious dogs, intravenous infusion of Formoterol Hemifumarate (0.5 μg/kg/min) caused a transient ~15% increase in heart rate (β1-mediated) without significant effects on systolic/diastolic blood pressure [2] In rats with lipopolysaccharide (LPS)-induced lung inflammation, subcutaneous injection of Formoterol Hemifumarate (0.3 μg/kg) reduced pulmonary edema by ~30% and inhibited neutrophil infiltration by ~28% [1] |
| Enzyme Assay |
β1/β2-adrenoceptor radioligand binding assay: Prepare membrane homogenates from HEK293 cells transfected with human β1 or β2 adrenoceptors. Incubate homogenates with [3H]-dihydroalprenolol (0.5 nM) and various concentrations of Formoterol Hemifumarate (0.001-100 nM) at 25°C for 90 minutes. Separate bound and free ligand by rapid filtration through glass fiber filters. Wash filters with ice-cold buffer and measure radioactivity using a scintillation counter. Calculate Ki values from competition binding curves [3]
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| Cell Assay |
Human bronchial smooth muscle cell cAMP assay: Culture human bronchial smooth muscle cells in DMEM supplemented with fetal bovine serum. Serum-starve cells for 24 hours, then treat with Formoterol Hemifumarate (0.1-10 nM) for 15 minutes. Lyse cells and measure cAMP levels using a competitive enzyme immunoassay. Normalize results to total protein concentration [1]
Guinea pig tracheal smooth muscle relaxation assay: Isolate guinea pig tracheal rings, mount in organ baths with oxygenated Krebs-Ringer solution at 37°C, and precontract with histamine (1 μM). Add Formoterol Hemifumarate (0.01-10 nM) cumulatively and record tension changes using an isometric transducer. Calculate relaxation percentage relative to baseline contraction [2] |
| Animal Protocol |
100 mg /mL
Guinea-pig Guinea pig allergic bronchospasm model: Adult guinea pigs are sensitized with ovalbumin (i.p.) and challenged with aerosolized ovalbumin to induce bronchospasm. Formoterol Hemifumarate is administered as an aerosol (0.1-1 μg/kg) 30 minutes after challenge. Airway resistance and dynamic lung compliance are measured using a plethysmograph [1] Conscious dog hemodynamic assay: Adult dogs are instrumented with arterial catheters for blood pressure monitoring and venous catheters for drug infusion. Formoterol Hemifumarate is dissolved in physiological saline and infused intravenously at 0.5 μg/kg/min for 30 minutes. Heart rate and systolic/diastolic blood pressure are recorded continuously [2] |
| ADME/Pharmacokinetics |
Absorption: Due to first-pass metabolism, the oral bioavailability of formoterol fumarate in humans is approximately 20-30%. After inhalation administration, the systemic absorption rate is approximately 10-15%, and the peak plasma concentration (Cmax) is reached 1-2 hours after inhalation [1]. Distribution: It is mainly distributed in bronchial tissues, and the volume of distribution (Vdss) in the human body is approximately 4-5 L/kg [1]. Metabolism: It is mainly metabolized in the liver through glucuronidation and O-dealkylation, generating inactive metabolites [2]. Excretion: The plasma elimination half-life (t1/2) in the human body is approximately 10-12 hours. Approximately 60% of the dose is excreted in the urine within 24 hours, of which less than 5% is the original drug [1]. Plasma protein binding rate: The plasma protein binding rate of formoterol fumarate in the human body is approximately 65% [2].
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| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Overview of medication use during lactation While there is currently no publicly available data on the use of inhaled formoterol during lactation, data on the related drug terbutaline suggest that only a very small amount of the drug is expected to be excreted into breast milk. Authors of multiple reviews and expert guidelines agree that the use of such drugs during lactation is acceptable due to the low bioavailability of inhaled bronchodilators and the low maternal serum concentrations after administration. ◉ Effects on breastfed infants No published information was found as of the revision date. ◉ Effects on lactation and breast milk No published information was found as of the revision date. Common adverse reactions in humans include tremor (occurrence approximately 18%), headache (approximately 12%), palpitations (approximately 10%), and muscle cramps (approximately 7%), which are dose-related and reversible [1][2]. The acute intravenous LD50 in mice is approximately 25 mg/kg; lethal doses can induce severe tachycardia and arrhythmias [1]. In a subchronic toxicity study in rats (28 days), with inhalation doses up to 5 μg/kg/day, no significant hepatotoxicity, nephrotoxicity, or hematological abnormalities were observed [2]. |
| References | |
| Additional Infomation |
Astrofloxacin fumarate is a fumarate salt prepared by reacting astrofloxacin with one molecule of fumaric acid. It is a β-adrenergic agonist and bronchodilator. It contains astrofloxacin (1+) and is the enantiomer of (S,S)-formoterol fumarate. Formoterol fumarate is the fumarate form of formoterol, a long-acting selective sympathomimetic β-receptor agonist with bronchodilatory activity. Formoterol fumarate binds to β2-adrenergic receptors in bronchial smooth muscle, stimulating intracellular adenylate cyclase, thereby increasing the production of cyclic adenosine monophosphate (cAMP). Elevated cAMP levels lead to bronchial smooth muscle relaxation, improved mucociliary clearance, and reduced release of mediators from inflammatory cells, especially mast cells. (NCI05) A long-duration adrenergic β-2 receptor agonist. It is used to control asthma and treat chronic obstructive pulmonary disease. See also: Formoterol fumarate (note moved to).
Formoterol fumarate is a long-acting, highly selective β2-adrenergic receptor agonist [1][2][3]. Its mechanism of action includes activating β2-adrenergic receptors to increase intracellular cAMP levels, thereby mediating bronchial smooth muscle relaxation, reducing lung inflammation and inhibiting airway hyperresponsiveness [1][2]. Clinically, it is used for long-term control of bronchial asthma and chronic obstructive pulmonary disease (COPD), as well as for acute relief of bronchospasm (due to its rapid onset of action) [1]. It has both rapid onset of action (within 15 minutes) and long duration of action (about 12 hours), so it can be administered twice daily for maintenance therapy [1][2]. Its high selectivity for β2-adrenergic receptors minimizes β1-mediated cardiovascular adverse reactions [3]. |
| Molecular Formula |
C19H24N2O4.1/2C4H4O4
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| Molecular Weight |
402.40
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| Exact Mass |
460.184
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| CAS # |
43229-80-7
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| Related CAS # |
Formoterol hemifumarate hydrate; 183814-30-4; Arformoterol; 67346-49-0; Formoterol-1; 73573-87-2; (S,S)-Formoterol; 67346-48-9; Arformoterol tartrate; 200815-49-2; Formoterol-d6; 1020719-45-2
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| PubChem CID |
53477580
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| Appearance |
White to off-white solid powder
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| Boiling Point |
603.2ºC at 760mmHg
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| Melting Point |
138-140ºC
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| Flash Point |
318.6ºC
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| LogP |
3.034
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| Hydrogen Bond Donor Count |
10
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
18
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| Heavy Atom Count |
58
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| Complexity |
507
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| Defined Atom Stereocenter Count |
4
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| SMILES |
C[C@H](CC1=CC=C(C=C1)OC)NC[C@@H](C2=CC(=C(C=C2)O)NC=O)O.C[C@H](CC1=CC=C(C=C1)OC)NC[C@@H](C2=CC(=C(C=C2)O)NC=O)O.C(=C/C(=O)O)\C(=O)O
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| InChi Key |
OBRNDARFFFHCGE-PERKLWIXSA-N
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| InChi Code |
InChI=1S/2C19H24N2O4.C4H4O4/c2*1-13(9-14-3-6-16(25-2)7-4-14)20-11-19(24)15-5-8-18(23)17(10-15)21-12-22;5-3(6)1-2-4(7)8/h2*3-8,10,12-13,19-20,23-24H,9,11H2,1-2H3,(H,21,22);1-2H,(H,5,6)(H,7,8)/b;;2-1+/t2*13-,19+;/m00./s1
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| Chemical Name |
(E)-but-2-enedioic acid;N-[2-hydroxy-5-[(1S)-1-hydroxy-2-[[(2S)-1-(4-methoxyphenyl)propan-2-yl]amino]ethyl]phenyl]formamide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.21 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.21 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: 2.5 mg/mL (6.21 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4851 mL | 12.4254 mL | 24.8509 mL | |
| 5 mM | 0.4970 mL | 2.4851 mL | 4.9702 mL | |
| 10 mM | 0.2485 mL | 1.2425 mL | 2.4851 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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