β2 adrenoceptor ( EC50 = 1 nM )
β2-adrenergic receptor (ADRB2). Olodaterol is a selective, long-acting β2-adrenoceptor agonist with an EC50 of 0.1 nM and pKi of 9.14 for human β2-adrenoceptor. It shows >250-fold selectivity over β1-adrenoceptors. Activation of β2 receptors in airway smooth muscle leads to bronchodilation through relaxation of bronchial smooth muscle.

Olodaterol (0.001~10 nM; fibroblasts) inhibits the motility and proliferation induced by growth factors [2]. Fibroblasts treated with olotadrol (0.1–10 nM) prevent the signaling cascade from being phosphorylated when FGF is present [2]. Concentration-dependently, olapadaterol (0.001~1000 nM; 30 minutes; fibroblasts) raises intracellular cAMP. With a maximum efficacy of 70% at 10 nM, oledacaterol (0 to 10 nM; 30 min; fibroblasts) increased PICP in a concentration-dependent manner. Olodaterol is selective for the β2-AR receptor and has a subnanomolar affinity for it (pKi=9.14) when compared to the β1-AR and β3-AR subtypes [2].

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In vitro, Olodaterol demonstrates potent and selective β2-adrenoceptor agonist activity with an EC50 of 0.1 nM for human β2-adrenoceptor and a pKi of 9.14. It shows >250-fold selectivity over β1-adrenoceptors. The compound's high potency and selectivity contribute to its long-acting bronchodilator effects in airway smooth muscle preparations.

Olodaterol (1 mg/kg; inhalation; day 21) attenuates TGF-β-induced pulmonary fibrosis and speeds up the weight return to control levels (day 21)[2]. After 0.5 hours, olodaterol (0.1 to 3 μg/kg; inhaled; 5h ) and olodaterol (0.3 and 0.6 μg/kg; inhaled; 24 hours)) induce about 60% anesthetic protection[3].

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In vivo, Olodaterol induces bronchodilation for up to 24 hours after dosing in patients with COPD. The compound is administered via inhalation and provides sustained bronchodilation with a once-daily dosing regimen. Its long duration of action and β2 selectivity make it an effective treatment for COPD, including chronic bronchitis and emphysema. Olodaterol is approved for clinical use in COPD.

Cell-free receptor binding assays for Olodaterol use membrane preparations from cells expressing recombinant human β2-adrenergic receptors. The compound is incubated with a radiolabeled β-adrenergic receptor ligand (e.g., [¹²⁵I]-iodocyanopindolol) at varying concentrations for 60-120 minutes at room temperature. Nonspecific binding is determined in the presence of an excess of unlabeled β-blocker. Bound and free radioactivity are separated by filtration, and Ki values are calculated from competition curves.

Cell Line: Fibroblasts
Concentration: 0.1~10 nM
Result: Interfered with FGF-induced phosphorylation of signalling cascades.

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In vitro cellular functional assays for Olodaterol use cell lines stably expressing the β2-adrenergic receptor (e.g., CHO-β2 or HEK-293-β2 cells). Cells are seeded in 96-well plates and treated with Olodaterol at concentrations ranging from 0.001 nM to 10 μM. Receptor activation is measured by monitoring cAMP accumulation via HTRF or ELISA-based cAMP assays. EC50 values are determined from dose-response curves. Selectivity over β1 is confirmed by testing the compound against β1-expressing cells.

Lung fibrosis C57BL/6 mice
1 mg/mL
Inhal.; 21 days

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In vivo efficacy studies are conducted in animal models of bronchoconstriction, such as guinea pig or rat models. Olodaterol is administered via inhalation or intravenous routes at doses typically ranging from 0.1-100 μg/kg. Bronchodilation is measured by assessing airway resistance, lung function parameters (e.g., FEV1, peak expiratory flow), or by measuring protection against bronchoconstrictor-induced airway narrowing. Duration of action is assessed by measuring bronchodilation at various time points after dosing.

Absorption, Distribution and Excretion
Following inhalation of olodartrol, peak plasma concentrations are typically reached within 10 to 20 minutes. In healthy volunteers, the absolute bioavailability of inhaled olodartrol is estimated at approximately 30%, compared to less than 1% after oral administration of a solution. Therefore, the systemic bioavailability of inhaled olodartrol depends primarily on pulmonary absorption, with any swallowed dose contributing negligibly to systemic exposure. Following intravenous administration of [14C]-labeled olodartrol, 38% of the radioactive dose was recovered in the urine and 53% in the feces. After intravenous administration, 19% of the unmetabolized olodartrol was recovered in the urine. Following oral administration, only 9% of olodartrol and/or its metabolites were recovered in the urine, while the majority (84%) were recovered in the feces. The high volume of distribution (1110 L) suggests extensive distribution in tissues.
The total clearance of olodaterol in healthy volunteers was 872 mL/min, and the renal clearance was 173 mL/min.
Metabolism/Metabolites

Olodaterol is primarily metabolized via direct glucuronidation and O-demethylation of the methoxy group. Of the six identified metabolites, only the unbound demethylated product binds to the β2 receptor. However, this metabolite is undetectable in plasma after prolonged inhalation of the recommended therapeutic dose. Cytochrome P450 isoenzymes CYP2C9 and CYP2C8 are involved in the O-demethylation of olodaterol, while the role of CYP3A4 is negligible; while uridine diphosphate glycosyltransferase isoenzymes UGT2B7, UGT1A1, 1A7, and 1A9 are involved in the formation of olodaterol glucuronide.
Biological Half-Life

The terminal half-life after intravenous injection is 22 hours. In contrast, the terminal half-life after inhalation is approximately 45 hours, indicating that the latter is primarily determined by absorption rather than elimination.

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Pharmacokinetic studies of Olodaterol demonstrate that the compound is administered via inhalation, with low systemic exposure due to its targeted delivery to the lungs. PK parameters such as Cmax, Tmax, AUC, half-life, and systemic bioavailability are determined in preclinical species and in clinical studies. The compound's long duration of action is related to its slow dissociation from the β2 receptor and its retention in lung tissue.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
While there is currently no published data on the use of olodaterol during lactation, data on the related drug terbutaline suggest that very small amounts are expected to be excreted into breast milk. Authors of multiple reviews 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 found as of the revision date. ◉ Effects on Lactation and Breast Milk
No published information found as of the revision date.

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Protein Binding The in vitro binding of olodaterol to human plasma proteins is concentration-independent, with a binding rate of approximately 60%.

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Toxicology studies of Olodaterol were conducted as part of its clinical development program. As a β2-adrenoceptor agonist, potential toxicities may include cardiovascular effects (tachycardia, palpitations), tremor, and hypokalemia. Standard toxicology studies (acute, subchronic, and chronic) were performed in rodents and non-human primates. The compound's safety profile was evaluated in clinical trials and is well-established for its approved indication of COPD.

[1]. Design, synthesis and biological evaluation of 8-(2-amino-1-hydroxyethyl)-6-hydroxy-1,4-benzoxazine-3(4H)-one derivatives as potent β2-adrenoceptor agonists. Bioorg Med Chem. 2020;28(1):115178.

[2]. Olodaterol shows anti-fibrotic efficacy in in vitro and in vivo models of pulmonary fibrosis. Br J Pharmacol. 2017;174(21):3848-3864.

[3]. Pharmacological characterization of olodaterol, a novel inhaled beta2-adrenoceptor agonist exerting a 24-hour-long duration of action in preclinical models [published correction appears in J Pharmacol Exp Ther. 2013 Jul;346(1):161]. J Pharmacol Exp Ther. 2010;334(1):53-62.

Olodaterol belongs to the benzoxazine class of compounds, with the chemical name 6-hydroxy-1,4-benzoxazine-3-one, where the hydrogen at position 4 is replaced by (1R)-1-hydroxy-2-{[1-(4-methoxyphenyl)-2-methylpropyl-2-yl]amino}ethyl. It (in hydrochloride form) is used for the long-term treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (including chronic bronchitis and/or emphysema). It is a β-adrenergic agonist and bronchodilator. It belongs to the benzoxazine class of compounds and is also a phenol, aromatic ether, secondary alcohol, and secondary amino compound. It is the conjugate base of olodaterol (1+). Olodaterol is a novel, long-acting β2-adrenergic agonist (LABA) that exerts its pharmacological effects by binding to and activating β2-adrenergic receptors primarily located in the lungs. β2-adrenergic receptors are membrane-bound receptors, normally activated by endogenous adrenaline. Adrenaline transmits signals via downstream L-type calcium channel interactions, mediating smooth muscle relaxation and bronchodilation. Receptor activation stimulates associated G proteins, which in turn activate adenylate cyclase, catalyzing the production of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA). Elevations in these two molecules induce bronchodilation by relaxing airway smooth muscle. Olodaterol is used to treat chronic obstructive pulmonary disease (COPD) and its characteristic progressive airflow obstruction through this mechanism. Bronchodilator therapy helps relieve related symptoms such as dyspnea, cough, and sputum production. Studies have shown that a single dose of olodaterol can improve forced expiratory volume in one second (FEV1) in COPD patients within 24 hours, thus allowing for once-daily dosing. Compared to short-acting bronchodilators and twice-daily LABAs, once-daily LABA treatment offers several advantages, including greater convenience and adherence, and improved airflow within 24 hours. Despite similar symptoms, olodartrol is not indicated for the treatment of acute exacerbations of COPD or asthma. Orodartrol is a β2-adrenergic agonist. The mechanism of action of olodartrol is as a β2-adrenergic agonist. See also: Orodartrol hydrochloride (active ingredient).

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Drug Indications
Olodartrol is indicated for the treatment of chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. It is not indicated for the treatment of acute exacerbations of COPD or asthma.
FDA LabelMechanism of Action
Olodartrol is a long-acting β2-adrenergic agonist (LABA) that exerts its pharmacological action by binding to and activating β2-adrenergic receptors, primarily located in the lungs. β2-adrenergic receptors are membrane-bound receptors that are normally activated by endogenous adrenaline. Adrenaline transmits signals through downstream L-type calcium channel interactions, mediating smooth muscle relaxation and bronchodilation. Upon receptor activation, it stimulates the associated G protein, which in turn activates adenylate cyclase, catalyzing the production of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA). Elevated levels of these two molecules induce bronchodilation by relaxing airway smooth muscle.

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Olodaterol (BI1744) is an FDA-approved long-acting beta2-adrenergic agonist (LABA) for the treatment of chronic obstructive pulmonary disease (COPD). It is marketed as a once-daily inhaled bronchodilator. The compound's high potency, β2 selectivity, and 24-hour duration of action make it an effective treatment option for COPD patients. Olodaterol is available for research purposes as well as for clinical use.

C21H26N2O5

386.44

386.184

C, 65.27; H, 6.78; N, 7.25; O, 20.70

868049-49-4

Olodaterol hydrochloride; 869477-96-3

11504295

Light yellow to khaki solid powder

1.3±0.1 g/cm3

649.0±55.0 °C at 760 mmHg

346.3±31.5 °C

0.0±2.0 mmHg at 25°C

1.596

1.17

4

6

7

28

521

1

[C@H](C1C=C(O)C=C2NC(COC=12)=O)(O)CNC(C)(C)CC1C=CC(OC)=CC=1

COUYJEVMBVSIHV-SFHVURJKSA-N

InChI=1S/C21H26N2O5/c1-21(2,10-13-4-6-15(27-3)7-5-13)22-11-18(25)16-8-14(24)9-17-20(16)28-12-19(26)23-17/h4-9,18,22,24-25H,10-12H2,1-3H3,(H,23,26)/t18-/m0/s1

6-hydroxy-8-[(1R)-1-hydroxy-2-[[1-(4-methoxyphenyl)-2-methylpropan-2-yl]amino]ethyl]-4H-1,4-benzoxazin-3-one

BI1744; BI-1744; OLODATEROL; 868049-49-4; BI-1,744; BI 1,744; 6-Hydroxy-8-[(1R)-1-hydroxy-2-[[2-(4-methoxyphenyl)-1,1-dimethylethyl]amino]ethyl]-2H-1,4-benzoxazin-3(4H)-one; BI 1744; Striverdi; Olodaterol

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)

DMSO: ~77 mg/mL (~199.3 mM)
Ethanol: ~40 mg/mL

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.

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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).

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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)

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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).

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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

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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.

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