Formoterol (also named as Arformoterol) is a long-acting β2 agonist (LABA) used in the treatment of asthma and COPD (chronic obstructive pulmonary disease). It is sold under several trade names, such as Atock, Atimos/Atimos Modulite, Foradil/Foradile, Oxeze/Oxis, and Perforomist, in three different forms: a dry powder inhaler, a metered-dose inhaler, and an inhalation solution. The combination formulations of mometasone/formoterol and budesonide/formoterol are also available for purchase. Compared to short-acting β2 agonists like salbutamol (albuterol), which have an efficacious duration of 4–6 hours, formoterol exhibits an extended duration of action (up to 12 hours). LABAs, like formoterol, are used in addition to prophylactic corticosteroid therapy as "symptom controllers." Since LABAs are not advised for the treatment of acute asthma, a "reliever" short-acting β2 agonist (such as salbutamol) is still needed.

Physicochemical Properties

Molecular Formula	C23H30N2O10
Molecular Weight	494.5
Exact Mass	494.19
Elemental Analysis	C, 55.87; H, 6.12; N, 5.67; O, 32.35
CAS #	200815-49-2
Related CAS #	Formoterol fumarate; 43229-80-7; Arformoterol; 67346-49-0; Arformoterol maleate; 1254575-18-2
PubChem CID	9827062
Appearance	Solid powder
Boiling Point	603.2ºC at 760mmHg
Vapour Pressure	2.12E-15mmHg at 25°C
LogP	1.2
Hydrogen Bond Donor Count	8
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	11
Heavy Atom Count	35
Complexity	521
Defined Atom Stereocenter Count	4
SMILES	C[C@@H](NC[C@H](O)C1=CC(NC=O)=C(O)C=C1)CC2=CC=C(OC)C=C2.O=C(O)[C@H](O)[C@@H](O)C(O)=O
InChi Key	FCSXYHUNDAXDRH-OKMNHOJOSA-N
InChi Code	InChI=1S/C19H24N2O4.C4H6O6/c1-13(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;5-1(3(7)8)2(6)4(9)10/h3-8,10,12-13,19-20,23-24H,9,11H2,1-2H3,(H,21,22);1-2,5-6H,(H,7,8)(H,9,10)/t13-,19+;1-,2-/m11/s
Chemical Name	(2R,3R)-2,3-dihydroxybutanedioic acid;N-[2-hydroxy-5-[(1R)-1-hydroxy-2-[[(2R)-1-(4-methoxyphenyl)propan-2-yl]amino]ethyl]phenyl]formamide
Synonyms	Formoterol; arformoterol; (R,R)-Formoterol; BD 40A; eformoterol; Foradil; formoterol fumarate; Trade names: Atock; Atimos/Atimos Modulite; Foradil/Foradile; Oxeze/Oxis; Perforomist
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Beta-2 adrenergic receptor ( Kd = 2.9 nM )
ln Vitro	In vitro activity: Arformoterol causes the accumulation of cAMP in human bronchial epithelial cells in culture[1].
ln Vivo	Arformoterol (R,R-formoterol) is an active racemic formoterol isomer that is prescribed for the long-term maintenance of bronchoconstriction in COPD patients, including those with emphysema and chronic bronchitis. The release of inflammatory mediators is inhibited by this potent and selective agent, which also relaxes the smooth muscles in the bronchi. Its pharmacological actions are due to the stimulation of intracellular adenyl cyclase, which raises intracellular cyclic adenosine monophosphate (cAMP) levels. Nebulizer administration of aerosolized betamethasone tartrate results in good pulmonary absorption. When COPD patients receive 15 µg arformoterol every 12 hours for 14 days, the mean peak plasma concentration (Cmax) and systemic exposure (AUC0-12h) are 4.3 pg/mL and 34.5 pg.h/mL, respectively. After taking medication, it takes about 30 minutes to reach the median steady state peak plasma concentration (tmax). When COPD patients receive 15 µg of inhaled arformoterol twice daily for 14 days, the mean terminal half-life is 26 hours. At doses of 0.25, 0.5, and 1.0 ng/mL of radiolabeled arformoterol, the binding of arformoterol to human plasma proteins in vitro ranges from 52 to 65%. The primary pathway of metabolism is direct conjugation, or glucuronidation, while the secondary pathway is O-demethylation. In addition to CYP2D6 and CYP2C19, at least five human uridine diphosphoglucuronosyltransferase (UGT) isozymes mediate metabolism. Within 48 hours following the oral administration of a single dose of radiolabeled arformoterol, 63% of the radioactive amount was found in the urine and 11% in the feces. Throughout the course of 14 days, 89% of the total radioactive dose was recovered, with 67% of it found in urine and 22% in feces[1].
Enzyme Assay	Formoterol(Arformoterol) is a brand-new, highly selective β2-adrenergic agonist that shows potential as a β2-agonist with selectively advantageous metabolic effects.
Animal Protocol	C57BL/6 male mice (8 wk old) 10 ng in 0.1 ml saline/20 g body weight instilled drop-wise in the external nares
References	[1]. Tropical Journal of Pharmaceutical Research, Vol. 9, No. 6, November-December, 2010, pp. 595-603. [2]. Am J Respir Cell Mol Biol. 2011 Jul; 45(1): 88–94.
Additional Infomation	Arformoterol Tartrate is the tartrate salt of arformoterol, the (R,R)-enantiomer of formoterol and a long-acting beta-2 adrenergic agonist with bronchodilator activity. Arformoterol selectively binds to and activates beta-2 adrenergic receptors in bronchiolar smooth muscle, thereby causing stimulation of adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). Increased intracellular cAMP levels cause relaxation of bronchial smooth muscle and lead to an inhibition of release of inflammatory mediators from mast cells. This may eventually lead to an improvement of airway function. See also: Arformoterol (has active moiety).

Solubility Data

Solubility (In Vitro)

DMSO: ~99 mg/mL (~200.2 mM) Water: N/A Ethanol: N/A

Solubility (In Vivo)

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 Formulations (e.g. IP/IV/IM/SC) 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). 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 Formulations 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). 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.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.0222 mL	10.1112 mL	20.2224 mL
	5 mM	0.4044 mL	2.0222 mL	4.0445 mL
	10 mM	0.2022 mL	1.0111 mL	2.0222 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.