Identification

Name
Bambuterol
Accession Number
DB01408
Type
Small Molecule
Groups
Approved, Investigational
Description

Bambuterol is a long acting beta-adrenoceptor agonist used in the treatment of asthma. It is a prodrug of terbutaline.

Structure
Thumb
Synonyms
  • (±)-5-(2-(tert-butylamino)-1-hydroxyethyl)-m-phenylene bis(dimethylcarbamate)
  • bambutérol
  • Bambuterol
  • Bambuterolum
Product Ingredients
IngredientUNIICASInChI Key
Bambuterol hydrochloride786Q84QZ3F81732-46-9LBARATORRVNNQM-UHFFFAOYSA-N
International/Other Brands
Bambec / Oxeol
Categories
UNII
Y1850G1OVC
CAS number
81732-65-2
Weight
Average: 367.44
Monoisotopic: 367.210721053
Chemical Formula
C18H29N3O5
InChI Key
ANZXOIAKUNOVQU-UHFFFAOYSA-N
InChI
InChI=1S/C18H29N3O5/c1-18(2,3)19-11-15(22)12-8-13(25-16(23)20(4)5)10-14(9-12)26-17(24)21(6)7/h8-10,15,19,22H,11H2,1-7H3
IUPAC Name
3-[2-(tert-butylamino)-1-hydroxyethyl]-5-[(dimethylcarbamoyl)oxy]phenyl N,N-dimethylcarbamate
SMILES
CN(C)C(=O)OC1=CC(=CC(OC(=O)N(C)C)=C1)C(O)CNC(C)(C)C

Pharmacology

Indication

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.

Pharmacodynamics

Bambuterol is a long acting beta2-adrenoceptor agonist used in the treatment of asthma. It is a prodrug of terbutaline. Bambuterol causes smooth muscle relaxation, resulting in dilation of bronchial passages.

Mechanism of action

The pharmacologic effects of bambuterol are at least in part attributable to stimulation through beta-adrenergic receptors (beta 2 receptors) of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic AMP. Increased cyclic 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.

TargetActionsOrganism
ABeta-2 adrenergic receptor
agonist
Human
Absorption

Bioavailability is 20% following oral administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic, extensive. Further metabolized to terbutaline by plasma cholinesterase.

Route of elimination
Not Available
Half life

13 hours for bambuterol and 21 hours for the primary active metabolite terbutaline.

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Bambuterol.
AcebutololThe therapeutic efficacy of Bambuterol can be decreased when used in combination with Acebutolol.
AcepromazineAcepromazine may decrease the vasoconstricting activities of Bambuterol.
AlclometasoneThe risk or severity of hypokalemia can be increased when Alclometasone is combined with Bambuterol.
AlfuzosinThe therapeutic efficacy of Bambuterol can be decreased when used in combination with Alfuzosin.
AlprenololAlprenolol may decrease the bronchodilatory activities of Bambuterol.
AmcinonideThe risk or severity of hypokalemia can be increased when Amcinonide is combined with Bambuterol.
AmineptineThe risk or severity of adverse effects can be increased when Amineptine is combined with Bambuterol.
AmitriptylineThe therapeutic efficacy of Bambuterol can be decreased when used in combination with Amitriptyline.
AmitriptylinoxideThe risk or severity of adverse effects can be increased when Amitriptylinoxide is combined with Bambuterol.
Food Interactions
Not Available

References

Synthesis Reference

Peter Jaksch, "Method of preparing an intermediate for the manufacture of bambuterol." U.S. Patent US5200551, issued May, 1986.

US5200551
General References
Not Available
External Links
Human Metabolome Database
HMDB0015478
KEGG Drug
D07377
PubChem Compound
54766
PubChem Substance
46505785
ChemSpider
49466
ChEBI
553827
ChEMBL
CHEMBL521589
Therapeutic Targets Database
DAP000250
PharmGKB
PA164743113
Wikipedia
Bambuterol
ATC Codes
R03CC12 — Bambuterol

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHigh Altitude Pulmonary Hypertension1
4CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)1
4Unknown StatusTreatmentCough Variant Asthma / Eosinophilic Bronchitis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.469 mg/mLALOGPS
logP1.69ALOGPS
logP1.4ChemAxon
logS-2.9ALOGPS
pKa (Strongest Acidic)13.91ChemAxon
pKa (Strongest Basic)9.52ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area91.34 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity98.28 m3·mol-1ChemAxon
Polarizability40.74 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8638
Blood Brain Barrier-0.761
Caco-2 permeable-0.6746
P-glycoprotein substrateSubstrate0.7076
P-glycoprotein inhibitor INon-inhibitor0.8708
P-glycoprotein inhibitor IINon-inhibitor0.8921
Renal organic cation transporterNon-inhibitor0.9451
CYP450 2C9 substrateNon-substrate0.7745
CYP450 2D6 substrateNon-substrate0.8167
CYP450 3A4 substrateNon-substrate0.5157
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9155
CYP450 2D6 inhibitorInhibitor0.8689
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.927
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9738
Ames testNon AMES toxic0.7909
CarcinogenicityNon-carcinogens0.762
BiodegradationNot ready biodegradable0.9963
Rat acute toxicity2.5730 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9727
hERG inhibition (predictor II)Non-inhibitor0.937
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0006-1290000000-f8e18061114ec89ffeda

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenoxy compounds. These are aromatic compounds contaning a phenoxy group.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Phenoxy compounds
Direct Parent
Phenoxy compounds
Alternative Parents
Aralkylamines / Carbamate esters / Secondary alcohols / Organic carbonic acids and derivatives / 1,2-aminoalcohols / Dialkylamines / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
show 1 more
Substituents
Phenoxy compound / Aralkylamine / Carbamic acid ester / 1,2-aminoalcohol / Carbonic acid derivative / Secondary alcohol / Secondary aliphatic amine / Secondary amine / Organic oxide / Alcohol
show 10 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
carbamate ester, phenylethanolamines (CHEBI:553827)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Protein homodimerization activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately ...
Gene Name
ADRB2
Uniprot ID
P07550
Uniprot Name
Beta-2 adrenergic receptor
Molecular Weight
46458.32 Da
References
  1. Rosberg B, Schroder C, Nyberg L, Rosenborg J, Wiren JE: Bambuterol and terbutaline in human cerebrospinal fluid and plasma. Eur J Clin Pharmacol. 1993;45(2):147-50. [PubMed:8223836]
  2. Svensson LA: Bambuterol, a bronchodilator prodrug with sustained action, enhances delivery of active drug to the lung. Agents Actions Suppl. 1988;23:271-6. [PubMed:3262993]
  3. Waldeck B: Beta-adrenoceptor agonists and asthma--100 years of development. Eur J Pharmacol. 2002 Jun 7;445(1-2):1-12. [PubMed:12065188]
  4. Coleman RA, Johnson M, Nials AT, Vardey CJ: Exosites: their current status, and their relevance to the duration of action of long-acting beta 2-adrenoceptor agonists. Trends Pharmacol Sci. 1996 Sep;17(9):324-30. [PubMed:8885698]
  5. Zhang D, Cheng M, Hyun MH, Xiong Z, Pan L, Li F: Enantiomeric separation of beta2-agonists on macrocyclic antibiotic chiral stationary phases in high performance liquid chromatography. Pharmazie. 2007 Nov;62(11):836-40. [PubMed:18065099]
  6. Chou YL, Wu CC, Wang HW: Effects of bambuterol and terbutaline on isolated rat's tracheal smooth muscle. Eur Arch Otorhinolaryngol. 2010 Aug;267(8):1305-11. doi: 10.1007/s00405-009-1173-7. Epub 2009 Dec 12. [PubMed:20012638]
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Identical protein binding
Specific Function
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name
BCHE
Uniprot ID
P06276
Uniprot Name
Cholinesterase
Molecular Weight
68417.575 Da
References
  1. Gazic I, Bosak A, Sinko G, Vinkovic V, Kovarik Z: Preparative HPLC separation of bambuterol enantiomers and stereoselective inhibition of human cholinesterases. Anal Bioanal Chem. 2006 Aug;385(8):1513-9. Epub 2006 Jul 25. [PubMed:16865342]

Drug created on July 17, 2007 06:34 / Updated on August 02, 2018 07:44