Levosalbutamol

Identification

Name
Levosalbutamol
Accession Number
DB13139  (DB05761)
Type
Small Molecule
Groups
Approved
Description

Levosalbutamol, also known as levalbuterol, is a short-acting β2 adrenergic receptor agonist used in the treatment of asthma and chronic obstructive pulmonary disease (COPD). Salbutamol has been marketed as a racemic mixture, although beta2-agonist activity resides almost exclusively in the (R)-enantiomer. The enantioselective disposition of salbutamol and the possibility that (S)-salbutamol has adverse effects have led to the development of an enantiomerically pure (R)-salbutamol formulation known as levosalbutamol (levalbuterol).

Structure
Thumb
Synonyms
  • (-)-Albuterol
  • (-)-Salbutamol
  • (R)-salbutamol
  • Levalbuterol
  • R-salbutamol
External IDs
ASF-1096
Product Ingredients
IngredientUNIICASInChI Key
Levalbuterol hydrochlorideWDQ1526QJM 50293-90-8OWNWYCOLFIFTLK-YDALLXLXSA-N
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
XopenexSolution, concentrate1.25 mg/.5mLRespiratory (inhalation)Akorn2015-02-26Not applicableUs
XopenexSolution1.25 mg/3mLRespiratory (inhalation)Remedy Repack2013-06-132017-11-04Us
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
LevalbuterolSolution.63 mg/3mLRespiratory (inhalation)Teva2013-04-29Not applicableUs
LevalbuterolSolution.63 mg/3mLRespiratory (inhalation)A S Medication Solutions2013-04-292017-06-20Us
LevalbuterolSolution.31 mg/3mLRespiratory (inhalation)The Ritedose Corporation2016-03-14Not applicableUs
LevalbuterolSolution.31 mg/3mLRespiratory (inhalation)Teva2013-04-29Not applicableUs
LevalbuterolSolution1.25 mg/3mLRespiratory (inhalation)Aurobindo Pharma2016-12-30Not applicableUs
LevalbuterolSolution.63 mg/3mLRespiratory (inhalation)The Ritedose Corporation2016-03-14Not applicableUs
LevalbuterolSolution1.25 mg/3mLRespiratory (inhalation)Teva2013-04-29Not applicableUs
LevalbuterolSolution.31 mg/3mLRespiratory (inhalation)Aurobindo Pharma2016-12-30Not applicableUs
LevalbuterolSolution, concentrate1.25 mg/.5mLRespiratory (inhalation)Aurobindo Pharma2017-01-31Not applicableUs
LevalbuterolSolution1.25 mg/3mLRespiratory (inhalation)The Ritedose Corporation2016-03-14Not applicableUs
LevalbuterolSolution.63 mg/3mLRespiratory (inhalation)Aurobindo Pharma2016-12-30Not applicableUs
Levalbuterol HydrochlorideSolution1.25 mg/3mLRespiratory (inhalation)Impax Generics2013-03-15Not applicableUs
Levalbuterol HydrochlorideSolution.31 mg/3mLRespiratory (inhalation)Impax Generics2013-03-15Not applicableUs
Levalbuterol HydrochlorideSolution.63 mg/3mLRespiratory (inhalation)Impax Generics2013-03-15Not applicableUs
Approved Over the Counter Products
Not Available
Unapproved/Other Products
Not Available
International/Other Brands
Not Available
Brand mixtures
Not Available
Categories
UNII
EDN2NBH5SS
CAS number
34391-04-3
Weight
Average: 239.3107
Monoisotopic: 239.152143543
Chemical Formula
C13H21NO3
InChI Key
NDAUXUAQIAJITI-LBPRGKRZSA-N
InChI
InChI=1S/C13H21NO3/c1-13(2,3)14-7-12(17)9-4-5-11(16)10(6-9)8-15/h4-6,12,14-17H,7-8H2,1-3H3/t12-/m0/s1
IUPAC Name
4-[(1R)-2-(tert-butylamino)-1-hydroxyethyl]-2-(hydroxymethyl)phenol
SMILES
CC(C)(C)NC[[email protected]](O)C1=CC(CO)=C(O)C=C1

Pharmacology

Indication

Levosalbutamol's bronchodilator properties give it indications in treatment of COPD (chronic obstructive pulmonary disease, also known as chronic obstructive lung disease) and asthma.

Structured Indications
Pharmacodynamics

Like other bronchodilators, it acts by relaxing smooth muscle in the bronchial tubes, and thus shortening or reversing an acute "attack" of shortness of breath or difficulty breathing.

Mechanism of action

Activation of β2 adrenergic receptors on airway smooth muscle leads to the activation of adenylate cyclase and to an increase in the intracellular concentration of 3',5'-cyclic adenosine monophosphate (cyclic AMP). The increase in cyclic AMP is associated with the activation of protein kinase A, which in turn, inhibits the phosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in muscle relaxation.

Levosalbutamol relaxes the smooth muscles of all airways, from the trachea to the terminal bronchioles. Increased cyclic AMP concentrations are also associated with the inhibition of the release of mediators from mast cells in the airways. Levosalbutamol acts as a functional agonist that relaxes the airway irrespective of the spasmogen involved, thereby protecting against all bronchoconstrictor challenges.

TargetActionsOrganism
ABeta-2 adrenergic receptor
agonist
Human
Absorption

Inhalation delivers the medication directly into the airways and lungs, thereby minimizing side effects because of reduced systemic absorption of the inhaled medications.

Volume of distribution
Not Available
Protein binding

plasma protein binding is relatively low.

Metabolism

Pure (R)-salbutamol formulation known as levosalbutamol is metabolised up to 12 times faster than (S)-salbutamol by intestine.

Route of elimination

excreted into the urine.

Half life

3.3 - 4 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
LoxapineThe risk or severity of adverse effects can be increased when Levosalbutamol is combined with Loxapine.Approved
Food Interactions
Not Available

References

Synthesis Reference
Not Available
General References
  1. Boulton DW, Fawcett JP: The pharmacokinetics of levosalbutamol: what are the clinical implications? Clin Pharmacokinet. 2001 Jan;40(1):23-40. [PubMed:11236808 ]
  2. Wikipedia [Link]
  3. Sciencedirect [Link]
External Links
KEGG Drug
D08124
KEGG Compound
C11770
ChemSpider
110192
BindingDB
50361247
ChEBI
8746
ChEMBL
CHEMBL1002
HET
68H
Wikipedia
Levalbuterol
ATC Codes
Not Available
AHFS Codes
Not Available
PDB Entries
Not Available
FDA label
Not Available
MSDS
Not Available

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentAsthma Bronchial3
3CompletedTreatmentAsthma Bronchial3
3CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)1
4CompletedHealth Services ResearchAsthma Bronchial / Chronic Obstructive Pulmonary Disease (COPD)1
4CompletedSupportive CareChronic Obstructive Pulmonary Disease (COPD) / Sepsis / Shock1
4CompletedTreatmentAsthma Bronchial4
4TerminatedTreatmentAcute Asthma1
4WithdrawnTreatmentAsthma Bronchial1
Not AvailableCompletedHealth Services ResearchChronic Obstructive Pulmonary Disease (COPD)1
Not AvailableEnrolling by InvitationBasic ScienceOxygen Consumption1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SolutionRespiratory (inhalation).63 mg/3mL
SolutionRespiratory (inhalation).31 mg/3mL
SolutionRespiratory (inhalation)1.25 mg/3mL
Solution, concentrateRespiratory (inhalation)1.25 mg/.5mL
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility2.15 mg/mLALOGPS
logP0.44ALOGPS
logP0.34ChemAxon
logS-2ALOGPS
pKa (Strongest Acidic)10.12ChemAxon
pKa (Strongest Basic)9.4ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area72.72 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity67.87 m3·mol-1ChemAxon
Polarizability26.87 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
LC-MS/MS Spectrum - Quattro_QQQ 10V, N/A (Annotated)LC-MS/MSsplash10-052r-4960000000-11e534d73f624db9d896
LC-MS/MS Spectrum - Quattro_QQQ 25V, N/A (Annotated)LC-MS/MSsplash10-0002-0900000000-1320ba6a3f38ebdb80a3
LC-MS/MS Spectrum - Quattro_QQQ 40V, N/A (Annotated)LC-MS/MSsplash10-002f-8900000000-4735e41255f39d1d99d4
Predicted LC-MS/MS Spectrum - 10V, PositivePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 20V, PositivePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 40V, PositivePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 10V, NegativePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 20V, NegativePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 40V, NegativePredicted LC-MS/MSNot Available
1H NMR Spectrum1D NMRNot applicable
[1H,13C] 2D NMR Spectrum2D NMRNot applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzyl alcohols. These are organic compounds containing the phenylmethanol substructure.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzyl alcohols
Direct Parent
Benzyl alcohols
Alternative Parents
Phenols and derivatives / Aralkylamines / Secondary alcohols / 1,2-aminoalcohols / Dialkylamines / Primary alcohols / Hydrocarbon derivatives / Aromatic alcohols
Substituents
Benzyl alcohol / Aralkylamine / Phenol / Secondary alcohol / 1,2-aminoalcohol / Secondary amine / Secondary aliphatic amine / Hydrocarbon derivative / Aromatic alcohol / Primary alcohol
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
albuterol (CHEBI:8746 )

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. UniProt [Link]
  2. KEGG [Link]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. UniProt [Link]
  2. ChEMBL [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. ChEMBL [Link]
  2. KEGG [Link]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. UniProt [Link]
  2. ChEMBL [Link]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. ChEMBL [Link]
  2. UniProt [Link]
Drug created on October 27, 2016 11:42 / Updated on September 01, 2017 12:28