Salbutamol targets the β2-adrenergic receptor, a G protein-coupled receptor expressed on airway smooth muscle cells. Upon binding, salbutamol activates the receptor, stimulating adenylyl cyclase to increase intracellular cAMP levels. Elevated cAMP activates protein kinase A, which leads to the relaxation of bronchial smooth muscle, bronchodilation, and inhibition of mast cell mediator release. Salbutamol has a high selectivity for β2-receptors over β1-receptors, minimizing cardiac effects.

In vitro, salbutamol causes concentration-dependent relaxation of precontracted airway smooth muscle in isolated tracheal or bronchial ring preparations, with an EC50 in the nanomolar range. It increases cAMP production in cultured airway smooth muscle cells. Salbutamol also inhibits the release of inflammatory mediators from mast cells and reduces ciliary beat frequency in airway epithelium. Its effects are reversed by β2-antagonists such as propranolol, confirming receptor-mediated activity.

In vivo, salbutamol produces rapid bronchodilation in patients with asthma and COPD, with onset of action within 5-15 minutes and duration of 4-6 hours. It is administered via inhalation to achieve local lung effects with minimal systemic side effects. Oral salbutamol is used for chronic maintenance but has more systemic effects. In animal models, salbutamol reverses bronchoconstriction induced by histamine, methacholine, or allergens. It also reduces airway hyperreactivity and improves lung function parameters.

In vitro enzyme/receptor binding assays for salbutamol are radioligand binding studies using membrane preparations from cells expressing human β1- or β2-adrenergic receptors. The compound's affinity (Ki) is determined by competitive displacement of a labeled ligand such as [3H]CGP-12177. Functional assays measure cAMP accumulation in cells treated with salbutamol; the EC50 for cAMP production is determined. Selectivity for β2 over β1 is calculated from potency differences.

In vitro cellular assays for salbutamol are performed using airway smooth muscle cells or transfected cell lines expressing β2-receptors. Cells are treated with varying concentrations of salbutamol, and intracellular cAMP levels are measured using ELISA or radioimmunoassay. Bronchodilator activity is assessed in isolated organ baths using tracheal rings contracted with carbachol or histamine; the relaxation induced by salbutamol is recorded. Cell viability and cytotoxicity are evaluated using standard assays.

In vivo animal experiments for salbutamol are conducted in guinea pigs, rats, or mice. Bronchoconstriction is induced by aerosolized histamine, methacholine, or antigen challenge. Animals are treated with salbutamol via inhalation or intravenous administration, and airway resistance or compliance is measured using whole-body plethysmography. The protective effect of salbutamol against bronchospasm is quantified. Pharmacokinetic and safety studies are performed in dogs and rodents to support clinical development.

Absorption, Distribution and Excretion
Following inhalation, salbutamol acts locally on bronchial smooth muscle, and the drug is initially undetectable in the blood. Blood concentrations decrease after 2 to 3 hours, likely due to some of the drug being swallowed and absorbed in the intestines. In particular, systemic concentrations of salbutamol are low after inhalation of the recommended dose. A trial in 12 healthy male and female subjects using a higher dose (1080 μg salbutamol base) showed that the mean peak plasma concentration after administration was approximately 3 ng/mL when using the propellant HFA-134a. The time to peak concentration (Tmax) was delayed (Tmax = 0.42 hours) after administration with VENTOLIN (salbutamol) HFA compared to a chlorofluorocarbon-propelled salbutamol inhaler (Tmax = 0.17 hours). Following oral administration, 58–78% of the dose is excreted in the urine within 24 hours, of which approximately 60% is excreted as metabolites. A small amount of the drug is excreted in the feces. The volume of distribution of salbutamol administered intravenously was recorded as 156 ± 38 L. The renal clearance of salbutamol after oral administration was 272 ± 38 mL/min, and after intravenous administration, it was 291 ± 70 mL/min. Furthermore, the renal clearance of the main sulfate-conjugated metabolite after oral administration was 98.5 ± 23.5 mL/min. Elimination routes: Kidney, 69% to 90% (of which 60% is excreted as metabolites). Feces, 4%. Extended-release tablets: After a single dose, the bioavailability is approximately 80% of that of the immediate-release tablet, regardless of whether it is taken with food; however, at steady state, the bioavailability is 100% of that of the immediate-release tablet. Food reduces the absorption rate but does not affect bioavailability. Absorption is rapid and good after oral administration. Time to peak effect: Syrup: within 2 hours. Tablets: 2 to 3 hours. It is unclear whether salbutamol is excreted into human breast milk.

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Metabolism/Metabolites
Salbutamol is not metabolized in the lungs, but is converted to 4'-O-sulfate (salbutamol 4'-O-sulfate) in the liver, with negligible pharmacological activity. It may also be metabolized via oxidative deamination and/or conjugation with glucuronide. Salbutamol is ultimately excreted in the urine as free drug and metabolites.
Sulfate conjugation metabolism to inactive 4'-O-sulfate is carried out by phenol sulfonyltransferase (PST). The (R)-enantiomer of salbutamol is more readily metabolized by PST (at a rate ten times higher) than its (S)-enantiomer.
It is hydrolyzed by esterases in tissues and blood to the active compound codeineol. The drug can also be conjugated to salbutamol 4'-O-sulfate.
Elimination route: Approximately 72% of the inhaled dose is excreted in the urine within 24 hours, of which 28% is the unchanged drug and 44% is metabolites.
Half-life: 1.6 hours
Biological half-life
The elimination half-life of inhaled or oral salbutamol has been recorded as 2.7 to 5 hours, while the apparent terminal plasma half-life of salbutamol has been recorded as approximately 4.6 hours.
Elimination: 3.8 to 6 hours.
Salbutamol has a molecular weight of 239.31 g/mol and a molecular formula of C13H21NO3. It is a white to off-white crystalline powder, freely soluble in ethanol and slightly soluble in water. After inhalation, about 10-20% of the dose reaches the airways, and the rest is swallowed and absorbed from the gut. The oral bioavailability is around 50%. Salbutamol is metabolized in the liver by sulfotransferases to its inactive sulfate conjugate. The plasma half-life is approximately 4-6 hours, and it is excreted primarily in urine.

Toxicity Summary
Salbutamol is a β2-adrenergic agonist, therefore it stimulates β2-adrenergic receptors. Salbutamol binds to β2-receptors in the lungs, leading to relaxation of bronchial smooth muscle. It is believed that salbutamol increases cAMP production by activating adenylate cyclase, and its effects are mediated by cAMP. Elevated intracellular cAMP levels increase the activity of cAMP-dependent protein kinase A, thereby inhibiting myosin phosphorylation and reducing intracellular calcium ion concentration. Decreased intracellular calcium ion concentration leads to smooth muscle relaxation and bronchodilation. In addition to its bronchodilation effect, salbutamol also inhibits the release of bronchodilators from mast cells, inhibits microvascular leakage, and enhances mucociliary clearance.

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Toxicity Data
LD₅₀ = 1100 mg/kg (oral in mice)

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Interactions
In healthy subjects treated with digoxin for 10 days, a 16-22% decrease in serum digoxin concentration was observed after a single intravenous or oral dose of salbutamol.

Adrenaline, other oral or inhaled sympathomimetic amines: May enhance sympathomimetic effects and increase the risk of toxicity. Avoid co-administration with salbutamol.

Monoamine oxidase inhibitors, tricyclic antidepressants: May cause serious cardiovascular adverse reactions and toxicity risks. Avoid co-administration with salbutamol.

Propranolol and other β-blockers: May antagonize the effects of salbutamol. Use with caution.

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Non-human Toxicity Values
Oral LD50 in mice > 2 g/kg

Salbutamol is generally well-tolerated. Common adverse effects include tremor, palpitations, headache, and muscle cramps, which are dose-dependent and more prominent with oral administration. At high doses, tachycardia and hypokalemia may occur. Serious allergic reactions are rare. Overuse can lead to paradoxical bronchospasm. Salbutamol is contraindicated in patients with severe hypersensitivity. It should be used with caution in patients with cardiovascular disease, hyperthyroidism, and diabetes.

Clin Sci (Lond).1986 Feb;70(2):159-65.

Therapeutic Uses
Bronchodilator; Tocolytic agent. Salbutamol…is indicated for the symptomatic treatment of bronchial asthma and for the treatment of reversible bronchospasm that may occur in conjunction with bronchitis, emphysema, and other obstructive airway diseases. (Included on US product label) Salbutamol is indicated for the temporary treatment of acute hyperkalemia in pediatric patients. /Not included on US product label/ /ExpTher/ Orally inhaled salbutamol has been investigated for the prevention or relief of muscle paralysis episodes in some patients with familial hyperkalemic periodic paralysis. Drug Warnings Tremor appears to be the most frequently reported adverse reaction to salbutamol, occurring in up to 20% of patients in clinical trials across various doses. Other common adverse reactions to salbutamol include nervousness, nausea, tachycardia, palpitations, chest pain, and dizziness. …
Salbutamol has been reported to cause maternal and fetal tachycardia and hyperglycemia (especially in diabetic patients), as well as maternal hypotension, acute congestive heart failure, pulmonary edema, and death.
Salbutamol may delay preterm delivery. Due to the potential interference with uterine contractions, caution is advised when using this product in pregnant women to treat bronchospasm.
Pregnancy risk level: C / Risk cannot be ruled out. Currently, adequate, well-controlled clinical studies are lacking, and animal studies have not shown any risk to the fetus or lack relevant data. Use of this product during pregnancy may cause harm to the fetus; however, the potential benefits may outweigh the potential risks. /
For more complete data on drug warnings for salbutamol (22 in total), please visit the HSDB record page.

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Pharmacodynamics
Salbutamol (INN) or abuterol (USAN) is a moderately selective β2-receptor agonist with a structure similar to terbutaline, widely used as a bronchodilator for the treatment of asthma and other chronic obstructive airway diseases. The R-isomer of levosalbutamol has a bronchodilatory effect, while the S-isomer increases bronchial reactivity. The R-enantiomer is marketed as pure levosalbutamol, and therefore, due to the presence of only the R-enantiomer, it may have fewer side effects—although this has not been formally confirmed. Following oral and parenteral administration, β-receptors (including β1 and β2 receptors) are stimulated in the body because (a) β-2 selectivity is not absolute, and (b) salbutamol concentrations are higher in these receptor regions under these routes of administration. This leads to β1 receptor-mediated cardiac excitatory effects (albeit less intense than isoproterenol), and β2 receptor-mediated peripheral vasodilation and hypotension, skeletal muscle tremor, and uterine muscle relaxation. Metabolic disturbances, such as hyperinsulinemia and hyperglycemia, may also occur, but it is unclear whether these disturbances are mediated by β1 or β2 receptors. Serum potassium levels tend to decrease.
Salbutamol is an FDA-approved medication available under many brand names, including Ventolin, Proventil, and Albuterol. It is classified as a short-acting β2-agonist (SABA) and is a first-line rescue medication for acute asthma attacks. It is also used off-label for hyperkalemia and tocolysis. The compound has been used clinically for over 50 years and is on the WHO Model List of Essential Medicines. Its safety and efficacy are well established, making it a cornerstone of respiratory therapy.

C13H21NO3

239.31

239.152

18559-94-9

Salbutamol hemisulfate;51022-70-9;Salbutamol-d3;1219798-60-3;Salbutamol-d9;1173021-73-2;Salbutamol-d9 acetate;1781417-68-2

2083

White to off-white solid powder

1.2±0.1 g/cm3

433.5±40.0 °C at 760 mmHg

157-158ºC

159.5±17.9 °C

0.0±1.1 mmHg at 25°C

1.566

0.01

4

4

5

17

227

0

NDAUXUAQIAJITI-UHFFFAOYSA-N

NDAUXUAQIAJITI-UHFFFAOYSA-N

4-[2-(tert-butylamino)-1-hydroxyethyl]-2-(hydroxymethyl)phenol

Salbutamol Albuterol Proventil Sultanol Aerolin Albuterol Sulfate Proventil Salbutamol Sultanol Ventolin

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 : ~100 mg/mL (~417.87 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (10.45 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (10.45 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (10.45 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)