Drug/Small Molecule:

salbutamol

Overview

Generic Names:	Albuterol; Albuterol Sulfate; Albuterol Sulphate; Levalbuterol; Salbutamol Sulfate; Salbutamol Sulphate
IUPAC Name:	4-[2-(tert-butylamino)-1-hydroxyethyl]-2-(hydroxymethyl)phenol
Trade Names:	Accuneb; Aerolin; Airomir; Asmaven; Asmol; Asthalin; Asthavent; Broncovaleas; Buventol; Cetsim; Cobutolin; Ecovent; Loftan; ProAir; Proventil; Rotahaler; Salamol; Salbulin; Salbutard; Salbutine; Salbuvent; Solbutamol; Sultanol; Venetlin; Ventalin Inhaler; Ventolin; Ventolin Inhaler; Ventolin Rotacaps; Volma; Volmax; Xopenex
Brand Mixtures:	Combivent (Ipratropium Bromide + Salbutamol Sulfate); Gen-Combo Sterinebs (Ipratropium Bromide + Salbutamol Sulfate)
PharmGKB Accession Id:	PA448068

Description

A racemic mixture with a 1:1 ratio of the r-isomer, levalbuterol, and s-albuterol. It is a short-acting beta2-adrenergic agonist with its main clinical use in asthma. [PubChem]

Indication

For relief and prevention of bronchospasm due to asthma, emphysema, and chronic bronchitis.

ATC Therapeutic Categories

• R03AC:Selective beta-2-adrenoreceptor agonists
• R03CC:Selective beta-2-adrenoreceptor agonists

Pharmacology and Interactions

Mechanism Of Action

Salbutamol is a beta(2)-adrenergic agonist and thus it stimulates beta(2)-adrenergic receptors. Binding of albuterol to beta(2)-receptors in the lungs results in relaxation of bronchial smooth muscles. It is believed that salbutamol increases cAMP production by activating adenylate cyclase, and the actions of salbutamol are mediated by cAMP. Increased intracellular cyclic AMP increases the activity of cAMP-dependent protein kinase A, which inhibits the phosphorylation of myosin and lowers intracellular calcium concentrations. A lowered intracellular calcium concentration leads to a smooth muscle relaxation. Increased intracellular cyclic AMP concentrations also cause an inhibition of the release of mediators from mast cells in the airways.

Pharmacology

Salbutamol (INN) or albuterol (USAN), a moderately selective beta(2)-receptor agonist similar in structure to terbutaline, is widely used as a bronchodilator to manage asthma and other chronic obstructive airway diseases. The R-isomer, levalbuterol, is responsible for bronchodilation while the S-isomer increases bronchial reactivity. The R-enantiomer is sold in its pure form as Levalbuterol. The manufacturer of levalbuterol, Sepracor, has implied (although not directly claimed) that the presence of only the R-enantiomer produces fewer side-effects.

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hydrolyzed by esterases in tissue and blood to the active compound colterol. The drug is also conjugatively metabolized to salbutamol 4'-O-sulfate.

Absorption

Systemic absorption is rapid following aerosol administration.

Half Life

1.6 hours

Toxicity

LD₅₀=1100 mg/kg (orally in mice)

Chemical Properties

Chemical Formula:

C₁₃H₂₁NO₃

SMILES Code:

CC(C)(C)NC[C@@H](C1=CC(=C(C=C1)O)CO)O

(Format: OpenEye Isomeric)

Molecular Weight ( average / monoisotopic )

239.3107 / 239.1521

Curated Annotations ()

1. rs1042713 at chr5:148186633 in ADRB2
   Subjects who are homozygous for Arg16 and who are on regular albuterol treatment reported to have lower morning peak flows compared with those who were not on regular albuterol treatment, suggesting that regular albuterol therapy may not be approporiate for Arg16 homozygous sugjects

   Variant Name:

   ADRB2: Gly16Arg; 46G>A; Arg16

   Related Drugs:

   salbutamol

   Related Diseases:

   Asthma

   Evidence:

   PMID:15500895
   

2. rs2781659 at chr6:131933513 in ARG1
   This variant is associated with acute response to inhaled ß agonists in both childhood and adult asthmatic patients.

   Related Drugs:

   budesonide, fluticasone propionate, nedocromil, salbutamol

   Related Diseases:

   Asthma

   Evidence:

   PMID:18617639
   

3. rs2267715 at chr7:30682612 in CRHR2
   This variant in the corticotropin-releasing hormone receptor-2 gene was associated with acute bronchodilator response in the 608-participant Childhood Asthma Management Program (CAMP), but was not found to be associated in the 427-participant Sepracor study or the 152-participant LODO trial. The mean ages of the participants in the CAMP, Sepracor, and Lodo cohorts were 8.9, 32.6, and 42.9 years of age, respectively. Only Caucasians were analyzed in each of these studies.

   Related Drugs:

   salbutamol, selective beta-2-adrenoreceptor agonists

   Related Diseases:

   Asthma

   Evidence:

   PMID:18408560
   

4. rs2284220 at chr7:30684628 in CRHR2
   This variant in the corticotropin-releasing hormone receptor-2 gene was associated with acute bronchodilator response in the 427-participant Sepracor study, but not in the 608-participant Childhood Asthma Management Program (CAMP) or the 152-participant LODO trial. The mean ages of the participants in the CAMP, Sepracor, and Lodo cohorts were 8.9, 32.6, and 42.9 years of age, respectively. Only Caucasians were analyzed in each of these studies.

   Related Drugs:

   salbutamol, selective beta-2-adrenoreceptor agonists

   Related Diseases:

   Asthma

   Evidence:

   PMID:18408560
   

5. rs7793837 at chr7:30693302 in CRHR2
   Risk or phenotype-associated allele: T Phenotype: The T variant of CRHR2 rs7793837 was associated with reduced acute bronchodilation response to short-acting beta2-agonist treatment in the CAMP and LODO studies but not the Sepracor study. Study size: 607 (CAMP); 152 (LODO); 427 (Sepracor) Study population/ethnicity: Caucasian children with asthma with a mean age of 8.83 years enrolled in the Childhood Asthma Management Program (CAMP); Adult Caucasian participants with asthma enrolled in the Clinical Trial of Low-Dose Theophylline and Montelukast conducted by the American Lung Association Asthma Clinical Research Centers (LODO); Adult Caucasian participants with asthma enrolled in a completed clinical trial conducted by Sepracor Inc. Significance metric(s): p = 0.003 (CAMP); p = 0.05 (LODO); p = 0.24 (Sepracor) Type of association: PD

   Variant Name:

   CRHR2: Intronic, downstream of exon beta 1b

   Related Drugs:

   salbutamol, selective beta-2-adrenoreceptor agonists

   Related Diseases:

   Asthma

   Evidence:

   PMID:18408560
   

6. rs255100 at chr7:30695433 in CRHR2
   This variant in the corticotropin-releasing hormone receptor-2 gene was associated with acute bronchodilator response in the 608-participant Childhood Asthma Management Program (CAMP), but was not found to be associated in the 427-participant Sepracor study or the 152-participant LODO trial. The mean ages of the participants in the CAMP, Sepracor, and Lodo cohorts were 8.9, 32.6, and 42.9 years of age, respectively. Only Caucasians were analyzed in each of these studies.

   Related Drugs:

   salbutamol, selective beta-2-adrenoreceptor agonists

   Related Diseases:

   Asthma

   Evidence:

   PMID:18408560
   

Curated Information

The following genes are in curated knowledge about this drug.

Non-Curated Information

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

• IL8
• ADRB2

PharmGKB Curated Pathways

• Sympathetic Nerve Pathway (Neuroeffector Junction)

Non-Curated Information

A list of non-curated publications that mention this drug along with other drugs is available.

Curated Information

The following diseases are in curated knowledge about this drug.

	Disease	Relationship	Evidence
	Asthma	CO PD PK FA GN	Publications, Variants
	Essential hypertension	PD       GN	Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

Curated Phenotype Datasets

These datasets are sorted alphabetically by title.

1. Bronchodilator response to beta agonist in asthmatics

   • 
   • 
   • 
   • 
   • PD

   Submitted by Richard Judson, PhD involving ADRB2, salbutamol, and Asthma

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

1. National Heart, Lung, and Blood Institute SNP Health Association Asthma Resource Project (SHARP). dbGaP ID: phs000166.v1.p1
2. Physicochemical determinants of human renal clearance
3. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease

Downloads

You must sign in before you can download data.

LinkOuts

Common Searches

Search PubMed
Search Medline Plus
Search PubChem
Search CTD

Non-Curated Publications

A list of non-curated publications that mention this drug is available.