Beta-2 adrenergic receptor (β₂-AR)

- In a biomimetic cell membrane model, terbutaline sulphate showed interaction with lipid bilayers, altering membrane fluidity and potentially enhancing its binding to β₂-AR [2]
- In RAW264.7 macrophages, terbutaline (10 μM) increased MKP-1 expression and reduced LPS-induced TNF-α production, indicating anti-inflammatory effects mediated by MKP-1 activation [3]
Terbutaline (0–10 μM, 1 h) increases the expression of MKP-1 in mouse macrophages that have been activated[3].

- In a randomized controlled trial (RCT) involving 60 pregnant women, terbutaline (0.25 mg subcutaneous injection every 20 minutes for 3 doses) was compared with nifedipine for tocolysis. Terbutaline showed comparable efficacy in delaying delivery but caused more maternal tachycardia and tremors [1]
- In ob/ob mice with diabetic polyneuropathy, terbutaline (1 mg/kg, intraperitoneal injection) reduced mechanical allodynia through activation of β₂-AR and δ opioid receptors, as demonstrated by reversal of effects with selective antagonists [4]
Terbutaline (intraperitoneal injection; 0.5 mg/kg; twice a day; 20 days) treatment can alleviate allodynia in ob/ob mice[4].

Cell Line: J774 macrophages
Concentration: 0-10 μM
Incubation Time: 1 hour
Result: Enhanced MKP-1 expression in J774 macrophages in a dose-dependent manner.

---

- β₂-AR binding assay: HEK293 cells transfected with β₂-AR were incubated with radiolabeled terbutaline. Specific binding was measured by filtration, and competition experiments with unlabeled agonists determined receptor affinity [2]
- Inflammatory cytokine assay: RAW264.7 cells treated with terbutaline (1-10 μM) were stimulated with LPS. TNF-α levels in culture supernatants were quantified by ELISA, showing dose-dependent reduction [3]

- Tocolysis model: Pregnant women (gestational age 28-34 weeks) received terbutaline (0.25 mg subcutaneous) or nifedipine (10 mg orally) every 20 minutes for 3 doses. Maternal heart rate, blood pressure, and uterine activity were monitored [1]
- Diabetic neuropathy model: ob/ob mice (8 weeks old) were treated with terbutaline (1 mg/kg, intraperitoneal) daily for 7 days. Mechanical allodynia was assessed using von Frey filaments, and spinal cord tissues were analyzed for β₂-AR and δ opioid receptor expression [4]

---

Adult male ob/ob mice
0.5 mg/kg
Intraperitoneal injection; 0.5 mg/kg; twice a day; 20 days

Absorption, Distribution and Excretion
Following subcutaneous injection of 0.5 mg terbutaline, the mean peak plasma concentration (Cmax) was 9.6 ± ng/mL, the median time to peak concentration (Tmax) was 0.5 hours, and the mean area under the curve (AUC) was 29.4 ± 14.2 hng/mL. Following oral administration of 5 mg terbutaline tablets, the mean peak plasma concentration (Cmax) was 8.3 ± 3.9 ng/mL, the median time to peak concentration (Tmax) was 2 hours, and the mean AUC was 54.6 ± 26.8 hng/mL. Following oral administration of 5 mg terbutaline solution, the mean peak plasma concentration (Cmax) was 8.6 ± 3.6 ng/mL, the median time to peak concentration (Tmax) was 1.5 hours, and the mean AUC was 53.1 ± 23.5 hng/mL. The bioavailability of orally administered terbutaline is 14-15%. 40% of orally administered terbutaline is excreted in the urine 72 hours later. The main metabolite in urine is terbutaline sulfate conjugate. 90% of injected terbutaline is excreted in the urine, approximately two-thirds of which is unchanged. Less than 1% of the terbutaline dose is excreted in the feces. The mean volume of distribution of terbutaline is 1.6 L/kg. The mean clearance of terbutaline is 3.0 mL/min/kg. Terbutaline undergoes sulfation or glucuronidation before excretion. The elimination half-life of orally administered terbutaline is 3.4 hours, while that of subcutaneously administered terbutaline is 2.9 hours.

---

- Oral bioavailability: 15±6%
- Plasma protein binding: 25%
- Half-life: 3-4 hours
- Toxicity/Toxicokinetics: - Common adverse reactions: tremor, tachycardia, headache, and hypokalemia
- Overdose symptoms: nausea, vomiting, ventricular arrhythmias, and metabolic acidosis
- Plasma protein binding: 25%

Effects During Pregnancy and Lactation
◉ Overview of Medication Use During Lactation
Maternal oral or inhaled terbutaline is unlikely to affect breastfed infants. Authors of multiple reviews and expert guidelines agree that its use during breastfeeding is acceptable due to the low bioavailability of inhaled bronchodilators and low maternal serum concentrations after administration. Terbutaline, as a tocolytic, may shorten the duration of breastfeeding. ◉ Effects on Breastfed Infants
Two papers reported on four infants aged 3 to 8 weeks who were breastfed while their mothers administered 2.5 or 5 mg of terbutaline orally three times daily. None of the infants showed signs of sympathetic excitation and all developed normally. These cases are also summarized in a third publication.
◉ Effects on Lactation and Breast Milk
A small retrospective study in Serbia found that mothers who received beta-agonists (fenoterol or phenobarbital) with similar pharmacological effects to terbutaline as tocolytics had shorter breastfeeding durations than mothers who did not receive tocolytics (4.5 months vs. 9.5 months). It is currently unclear whether terbutaline has a similar effect.
A study at an Australian hospital compared breastfeeding outcomes in women who underwent cesarean sections in two phases. In the first phase, women undergoing grade I or II cesarean sections did not receive terbutaline treatment preoperatively (n = 423). In the second phase, all women undergoing grade I or II cesarean sections received a subcutaneous injection of 250 micrograms of terbutaline as a tocolytic, unless there were contraindications at the time of the decision to perform the cesarean section (n = 253). Breastfeeding rates at discharge were 95% in the first phase and 99% in the second phase. The difference was statistically significant.

---

Protein Binding
Terbutaline has a low protein binding rate in plasma.

[1]. Nifedipine versus terbutaline for tocolysis in external cephalic version. Int J Gynaecol Obstet. 2008 Sep;102(3):263-6.

[2]. The interaction of a β2 adrenoceptor agonist drug with biomimetic cell membrane models: The case of terbutaline sulphate. Life Sci. 2021 Nov 15;285:119992.

[3]. Anti-Inflammatory Effects of β2-Receptor Agonists Salbutamol and Terbutaline Are Mediated by MKP-1. PLoS One. 2016 Feb 5;11(2):e0148144.

[4]. The antiallodynic action of nortriptyline and terbutaline is mediated by β(2) adrenoceptors and δ opioid receptors in the ob/ob model of diabetic polyneuropathy. Brain Res. 2014 Feb 10;1546:18-26.

Terbutaline belongs to the phenylethanolamine class of compounds, with its structure consisting of catechol substituted at the 5-position with 2-(tert-butylamino)-1-hydroxyethyl. It possesses a variety of pharmacological activities, including β-adrenergic agonist, EC 3.1.1.7 (acetylcholinesterase) inhibitor, anti-asthmatic, bronchodilator, sympathomimetic, tocolytic, and hypoglycemic agent. It belongs to the phenylethanolamine and resorcinol classes of compounds. Terbutaline was first synthesized in 1966 and reported in the literature in the late 1960s and early 1970s. It is a selective β2-adrenergic agonist, commonly used to treat bronchodilation in asthmatic patients. Terbutaline was approved by the U.S. Food and Drug Administration (FDA) on March 25, 1974. Terbutaline is an ethanolamine derivative with bronchodilatory and tocolytic effects. Terbutaline selectively binds to and activates β2-adrenergic receptors, activating intracellular adenylate cyclase via trimeric G protein, subsequently increasing the production of cyclic adenosine monophosphate (cAMP). Elevated cAMP levels mediate bronchial and vascular smooth muscle relaxation by activating protein kinase A (PKA), which phosphorylates proteins that control muscle tone. cAMP also inhibits intracellular calcium ion release, reduces calcium ion influx into cells, and induces intracellular calcium ion chelation, all of which contribute to airway muscle relaxation. Terbutaline also increases mucociliary clearance and reduces the release of inflammatory cytokines. A selective β2-adrenergic agonist used as a bronchodilator and uterine contraction inhibitor. See also: Terbutaline sulfate (in saline form). Drug Indications Terbutaline is indicated for the prevention and reversal of bronchospasm in patients aged 12 years and older with asthma and reversible bronchospasm associated with bronchitis and emphysema. Mechanism of Action Terbutaline is a selective β2-adrenergic receptor agonist. Activation of these receptors in the bronchioles activates adenylate cyclase, increasing intracellular cyclic adenosine monophosphate (cAMP) levels. Elevated cAMP levels decrease intracellular calcium ion concentration, activate protein kinase A, inhibit myosin light chain kinase, activate myosin light chain phosphatase, ultimately relaxing the smooth muscle of the bronchioles. Pharmacodynamics Terbutaline is a β2-adrenergic receptor agonist indicated for the treatment of reversible bronchospasm in patients with asthma accompanied by bronchitis and emphysema. Because the inhaled formulation can be taken up to three times daily, it has a shorter duration of action and a wider therapeutic window. Terbutaline is a selective β2-adrenergic receptor agonist used to relieve bronchospasm and inhibit uterine contractions. Activation of its β2-adrenergic receptors can lead to cAMP-mediated smooth muscle relaxation and anti-inflammatory effects [10][12]
- FDA warnings include cardiovascular risks (e.g., arrhythmias) and potential complications from preterm birth [4]

C12H19NO3

225.288

225.136

C, 63.98; H, 8.50; N, 6.22; O, 21.30

23031-25-6

Terbutaline sulfate; 23031-32-5; Terbutaline-d9; 1189658-09-0; Terbutaline-d3

5403

White to off-white crystalline powder

1.171 g/cm3

419.2ºC at 760 mmHg

204-208ºC

165.3ºC

3.42E-07mmHg at 25°C

1.4596 (estimate)

1.91

4

4

4

16

205

0

CC(C)(C)NCC(C1=CC(=CC(=C1)O)O)O

XWTYSIMOBUGWOL-UHFFFAOYSA-N

InChI=1S/C12H19NO3/c1-12(2,3)13-7-11(16)8-4-9(14)6-10(15)5-8/h4-6,11,13-16H,7H2,1-3H3

5-[2-(tert-butylamino)-1-hydroxyethyl]benzene-1,3-diol

Bricaril; Bricyn; KWD 2019; terbutaline; 23031-25-6; Terbutalin; Terbutalina; Terbutalinum; Asthmasian; 5-[2-(tert-butylamino)-1-hydroxyethyl]benzene-1,3-diol; 1,3-Benzenediol, 5-[2-[(1,1-dimethylethyl)amino]-1-hydroxyethyl]-; KWD-2019; KWD2019; Terbutaline

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: ~250 mg/mL (~1109.7 mM)

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.)