TERBUTALINE

First approved in 1974

Details

Stereochemistry	RACEMIC
Molecular Formula	C12H19NO3
Molecular Weight	225.2842
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=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

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00871
Curator's Comment: Description was created based on several sources, including

Terbutaline is a relatively selective beta2-adrenergic bronchodilator that has little or no effect on alpha-adrenergic receptors. The drug has exerts a preferential effect on beta2-adrenergic receptors but stimulates beta-adrenergic receptors less selectively than relatively selective beta2-agonists. Terbutaline appears to have a greater stimulating effect on beta-receptors of the bronchial, vascular, and uterine smooth muscles (beta2 receptors) than on the beta-receptors of the heart (beta1 receptors). This drug relaxes smooth muscle and inhibits uterine contractions, but may also cause some cardiostimulatory effects and CNS stimulation. The pharmacologic effects of terbutaline are at least in part attributable to stimulation through beta-adrenergic receptors of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic- 3',5'- adenosine monophosphate (c-AMP). Increased c-AMP levels are associated with relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells. Terbutaline is used for the prevention and reversal of bronchospasm in patients 12 years of age and older with reversible, obstructive airway disease, as well as symptomatic management of reversible bronchospasm associated with bronchitis and emphysema. Also used acute IV and sub-Q therapy in selected women to inhibit uterine contractions in preterm labor (tocolysis) and prolong gestation when beneficial.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Beta-2 adrenergic receptor 203 Target ID: CHEMBL210 Sources: http://www.drugbank.ca/drugs/DB00871	Agonist 2662		3.16 µM [EC50]
cAMP biosynthetic process 6 Target ID: GO:0006171 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10516654	Partial Agonist 288		2.3 µM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Asthma 237 Sources: https://www.drugs.com/pro/terbutaline.html	Preventing		Approved 8360	Terbutaline SULFATE Approved Use indicated for the prevention and reversal of bronchospasm in patients 12 years of age and older with asthma and reversible bronchospasm associated with bronchitis and emphysema. Launch Date 1.41851519E12

C_max

Value	Dose	Co-administered	Analyte	Population
24 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2706188/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:		TERBUTALINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
148.6 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2706188/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:		TERBUTALINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
13.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2706188/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:		TERBUTALINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
2 mg single, transdermal Overdose Dose: 2 mg Route: transdermal Route: single Dose: 2 mg Sources: https://pubmed.ncbi.nlm.nih.gov/8400938	unhealthy, 15 years n = 1 Health Status: unhealthy Age Group: 15 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/8400938	Other AEs: Tachycardia, Systolic murmur... Other AEs: Tachycardia (1 patient) Systolic murmur (1 patient) Tremor (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/8400938
50 mg single, oral Overdose Dose: 50 mg Route: oral Route: single Dose: 50 mg Sources: https://pubmed.ncbi.nlm.nih.gov/7793711	pregnant, 21 years n = 1 Health Status: pregnant Age Group: 21 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/7793711	Other AEs: Abdominal pain, Jitteriness... Other AEs: Abdominal pain (1 patient) Jitteriness (1 patient) Palpitations (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/7793711
500 mg single, oral Overdose Dose: 500 mg Route: oral Route: single Dose: 500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/3692499	unhealthy, 22 years Health Status: unhealthy Age Group: 22 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/3692499	Other AEs: Nausea, Tachycardia... Other AEs: Nausea (1 patient) Tachycardia (1 patient) Tremor (1 patient) Hyperglycemia (1 patient) Hypokalemia (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/3692499
2.5 mg single, subcutaneous Overdose Dose: 2.5 mg Route: subcutaneous Route: single Dose: 2.5 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6102210	pregnant, 35 years n = 1 Health Status: pregnant Age Group: 35 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6102210	Other AEs: Tachycardia... Other AEs: Tachycardia (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/6102210
10 mg 3 times / day multiple, oral Highest studied dose Dose: 10 mg, 3 times / day Route: oral Route: multiple Dose: 10 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2806513	unhealthy, 56 years (range: 44-68 years) n = 12 Health Status: unhealthy Condition: bronchial asthma Age Group: 56 years (range: 44-68 years) Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/2806513	Other AEs: Tremor, Palpitation... Other AEs: Tremor Palpitation Sources: https://pubmed.ncbi.nlm.nih.gov/2806513
10 ug/kg single, intravenous (starting) Dose: 10 ug/kg Route: intravenous Route: single Dose: 10 ug/kg Sources: https://pubmed.ncbi.nlm.nih.gov/10891825	unhealthy, 9.1 years n = 29 Health Status: unhealthy Condition: severe asthma Age Group: 9.1 years Sex: M+F Population Size: 29 Sources: https://pubmed.ncbi.nlm.nih.gov/10891825	Other AEs: Cardiotoxicity... Other AEs: Cardiotoxicity (3 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/10891825

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 1599

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
		Cav1.2 4

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
Cav1.2 49	inducer 27 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0024320509003361 Page: 570.0
hERG 1632	inhibitor 1613 Sources: https://link.springer.com/article/10.1007/s10928-018-9583-z Page: 6.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:9449	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9449
ChemicalBook	CB02131227	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB02131227
MolPort	MolPort-003-850-418	https://www.molport.com/shop/molecule-link/MolPort-003-850-418
eMolecules	27524076	https://www.emolecules.com/cgi-bin/more?vid=27524076
eMolecules	31228026	https://www.emolecules.com/cgi-bin/more?vid=31228026

PubMed

Title	Date	PubMed
Enhanced responsiveness of the myocardial beta-adrenoceptor-adenylate cyclase system in the perfused rat heart (I).	1998 Oct	10192281
Effects of terbutaline on force and intracellular calcium in slow-twitch skeletal muscle fibres of the rat.	1999 Apr	10372813
Effect of beta(2)-adrenoceptor activation and angiotensin II on tumour necrosis factor and interleukin 6 gene transcription in the rat renal resident macrophage cells.	1999 Oct	10525314
Functional, biochemical and molecular biological evidence for a possible beta(3)-adrenoceptor in human near-term myometrium.	2000 Aug	10952688
beta(2)-adrenoceptor agonist suppresses renal tumour necrosis factor and enhances interleukin-6 gene expression induced by endotoxin.	2000 Dec	11096136
beta-adrenergic stimulation restores rat lung ability to clear edema in ventilator-associated lung injury.	2000 Jul	10903255
Pharmacokinetics and pharmacodynamics of terbutaline in healthy horses.	2000 Jul	10895896
Beta2-adrenoceptor agonist suppresses tumour necrosis factor production in rat mesangial cells.	2000 May	10857765
Systemic capillary leak syndrome preceding plasma cell leukaemia.	2001	11713377
Bronchodilators for the prevention and treatment of chronic lung disease in preterm infants.	2001	11687053
Treatment of fetal congenital complete heart block with maternal administration of beta-sympathomimetics (terbutaline): a case report.	2001	11586045
Choices of therapy for exercise-induced asthma in children.	2001	11421936
Age- and gender-specific asthma death rates in patients taking long-acting beta2-agonists: prescription event monitoring pharmacosurveillance studies.	2001	11368253
beta2-Adrenoceptor desensitization in human alveolar macrophages induced by inhaled terbutaline in vivo is not counteracted by budesonide.	2001 Apr	11256987
Contribution of amiloride-insensitive pathways to alveolar fluid clearance in adult rats.	2001 Apr	11247951
Antibacterial activity of apical surface fluid from the human airway cell line Calu-3: pharmacologic alteration by corticosteroids and beta(2)-agonists.	2001 Aug	11509329
Discriminative capacity of bronchodilator response measured with three different lung function techniques in asthmatic and healthy children aged 2 to 5 years.	2001 Aug 15	11520714
Efficacy and safety of Ascoril in the management of cough--National Study Group report.	2001 Feb	11482804
Beta1-adrenergic agonist is a potent stimulator of alveolar fluid clearance in hyperoxic rat lungs.	2001 Feb	11286398
Effects of the perfusion of beta-, beta2-, or beta3-adrenergic agonists or epinephrine on in situ adipose tissue lipolysis measured by microdialysis in underfed ewes.	2001 Feb	11219455
Blunted cardiac responses to receptor activation in subjects with Thr164Ile beta(2)-adrenoceptors.	2001 Feb 27	11222464
The efficacy of terbutaline and magnesium sulfate in the management of preterm labor.	2001 Jan	11281506
Clinical characteristics of asthmatic patients prescribed various beta-agonist metered-dose inhalers at Yamagata University Hospital.	2001 Jan	11201164
Involvement of beta1- and beta2- but not beta3-adrenoceptor activation in adrenergic PYY secretion from the isolated colon.	2001 Jan	11139781
Denopamine, a beta(1)-adrenergic agonist, increases alveolar fluid clearance in ex vivo rat and guinea pig lungs.	2001 Jan	11133887
A single bout of exercise induces beta-adrenergic desensitization in human adipose tissue.	2001 Jan	11124148
Protection against cold air and exercise-induced bronchoconstriction while on regular treatment with Oxis.	2001 Jun	11421506
Adrenergic regulation of ion transport across adult alveolar epithelial cells: effects on Cl- channel activation and transport function in cultures with an apical air interface.	2001 Jun 1	11420606
Attenuation of insulin resistance by chronic beta2-adrenergic agonist treatment possible muscle specific contributions.	2001 Jun 22	11510954
On-demand relief treatment for asthma.	2001 Jun 9	11417575
FeNO measured at fixed exhalation flow rate during controlled tidal breathing in children from the age of 2 yr.	2001 Mar	11254527
Comparison of the acute effects of salbutamol and terbutaline on heart rate variability in adult asthmatic patients.	2001 May	11488317
Effects of terbutaline on NGF formation in allergic inflammation of the rat.	2001 May	11325809
Efficacy of 'functional relaxation' in comparison to terbutaline and a 'placebo relaxation' method in patients with acute asthma. A randomized, prospective, placebo-controlled, crossover experimental investigation.	2001 May-Jun	11340417
Hypoxia reduces alveolar epithelial sodium and fluid transport in rats: reversal by beta-adrenergic agonist treatment.	2001 Nov	11713096
Beta-adrenoceptor signaling in the developing brain: sensitization or desensitization in response to terbutaline.	2001 Nov 26	11718842
Perinatal factors associated with severe intracranial hemorrhage.	2001 Oct	11641666
Sulindac to prevent recurrent preterm labor: a randomized controlled trial.	2001 Oct	11576567
Fatal adverse drug events: the paradox of drug treatment.	2001 Oct	11576320
Regulation of fetal cardiac and hepatic beta-adrenoceptors and adenylyl cyclase signaling: terbutaline effects.	2001 Oct	11557613
Lung deposition and protective effect of terbutaline delivered from pressurized metered-dose inhalers and the Turbuhaler in asthmatic individuals.	2001 Oct 15	11704585
Uterine contractility: vaginal administration of the beta-adrenergic agonist, terbutaline. Evidence of direct vagina-to-uterus transport.	2001 Sep	11594537
Fast enantiomeric separation of basis drugs by electrokinetic chromatography. Application to the quantitation of terbutaline in a pharmaceutical preparation.	2001 Sep	11589279
A cost-effectiveness study comparing the as-needed use of formoterol (Oxis) and terbutaline (Bricanyl) in patients with moderate to severe asthma.	2001 Sep	11575897

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Asthma - Maintenance Tablets: 5 mg orally 3 times a day at 6 hour intervals during waking hours. May decrease to 2.5 mg/dose if side effects are pronounced. Do not exceed 15 mg in 24 hours. Inhalation aerosol: 2 inhalations separated by 60 seconds every 4 to 6 hours. Do not repeat more often than every 4 to 6 hours. Usual Adult Dose for Asthma - Acute Inhalation aerosol: 2 inhalations separated by 60 seconds every 4 to 6 hours. Do not repeat more often than every 4 to 6 hours. Subcutaneous Injection: 0.25 mg into the lateral deltoid area. A second 0.25 mg dose can be administered in 15 to 30 minutes if needed. Do not exceed 0.5 mg in 4 hours. Continuous intravenous infusion: 0.08 to 6 mcg/kg/min.

Route of Administration: Other

In Vitro Use Guide

Terbutaline elicited a relaxation response in isolated rat's tracheal smooth muscle at a dose of 10(-6) M or more

Name

Type

Language

TERBUTALINE

Official Name

English

TERBUTALIN

Common Name

English

(RS)-5-(2-(TERT-BUTYLAMINO)-1-HYDROXYETHYL)BENZENE-1,3-DIOL

Systematic Name

English

ASTHMASIAN

Brand Name

English

TERBUTALINE [MI]

Common Name

English

5-[2-[(1,1-Dimethylethyl)amino]-1-hydroxyethyl]-1,3-benzenediol

Systematic Name

English

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

Systematic Name

English

BAMBUTEROL HYDROCHLORIDE IMPURITY A [EPIMPURITY]

Common Name

English

1,3-Benzenediol, 5-[2-[(1,1-dimethylethyl)amino]-1-hydroxyethyl]-

Systematic Name

English

TERBUTALINE [VANDF]

Common Name

English

terbutaline [INN]

Common Name

English

Terbutaline [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C48149