QuickView for formoterol (compound)

Summary
General Info

PubChem

PubChem Compound 11957546

Name:	formoterol
PubChem Compound ID:	11957546
Molecular formula:	C₄₂H₅₂N₄O₁₂
Molecular weight:	804.882 g/mol
Synonyms:	EU-0100498

DrugBank

Identification

Name:	formoterol
Name (isomeric):	DB00983
Drug Type:	small molecule
Synonyms:	Formoterolum [INN-Latin]; Formoterol fumarate
Brand:	Oxeze Turbuhaler, Oxis, Foradil, Oxeze Turbuhaler Foradil, Foradile
Brand name mixture:	Symbicort 100 Turbuhaler(Budesonide + Formoterol Fumarate Dihydrate), Symbicort 200 Turbuhaler(Budesonide + Formoterol Fumarate Dihydrate)
Category:	Sympathomimetic, Adrenergic beta-Agonists, Bronchodilator Agents
CAS number:	73573-87-2

Pharmacology

Indication:	For use as long-term maintenance treatment of asthma in patients 6 years of age and older with reversible obstructive airways disease, including patients with symptoms of nocturnal asthma, who are using optimal corticosteroid treatment and experiencing regular or frequent breakthrough symptoms requiring use of a short-acting bronchodilator. Not indicated for asthma that can be successfully managed with occasional use of an inhaled, short-acting beta2-adrenergic agonist. Also used for the prevention of exercise-induced bronchospasm, as well as long-term treatment of bronchospasm associated with COPD.
Pharmacology:	Formoterol is a long-acting selective beta2-adrenergic receptor agonist (beta2-agonist). Inhaled formoterol fumarate acts locally in the lung as a bronchodilator. In vitro studies have shown that formoterol has more than 200-fold greater agonist activity at beta2-receptors than at beta1- receptors. Although beta2-receptors are the predominant adren... show more » Formoterol is a long-acting selective beta2-adrenergic receptor agonist (beta2-agonist). Inhaled formoterol fumarate acts locally in the lung as a bronchodilator. In vitro studies have shown that formoterol has more than 200-fold greater agonist activity at beta2-receptors than at beta1- receptors. Although beta2-receptors are the predominant adrenergic receptors in bronchial smooth muscle and beta1-receptors are the predominant receptors in the heart, there are also beta2-receptors in the human heart comprising 10%-50% of the total beta-adrenergic receptors. The precise function of these receptors has not been established, but they raise the possibility that even highly selective beta2- agonists may have cardiac effects. show less «
Mechanism of Action:	The pharmacologic effects of beta2-adrenoceptor agonist drugs, including formoterol, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3', 5'-adenosine monophosphate (cyclic AMP). Increased cyclic AMP levels cause relaxation of bronchi... show more » The pharmacologic effects of beta2-adrenoceptor agonist drugs, including formoterol, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3', 5'-adenosine monophosphate (cyclic AMP). Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibits the release of pro-inflammatory mast-cell mediators such as histamine and leukotrienes. Formoterol also inhibits histamine-induced plasma albumin extravasation in anesthetized guinea pigs and inhibits allergen-induced eosinophil influx in dogs with airway hyper-responsiveness. The relevance of these in vitro and animal findings to humans is unknown. show less «
Absorption:	Rapidly absorbed into plasma following administration by oral inhalation. It is likely that the majority of the inhaled formoterol delivered is swallowed and then absorbed from the gastrointestinal tract.
Protein binding:	The binding of formoterol to human plasma proteins in vitro was 61%-64% at concentrations from 0.1 to 100 ng/mL. Binding to human serum albumin in vitro was 31%-38% over a range of 5 to 500 ng/mL. The concentrations of formoterol used to assess the plasma protein binding were higher than those achieved in plasma following inhalation of a single 120 µg dose.
Biotransformation:	Metabolized primarily by direct glucuronidation at either the phenolic or aliphatic hydroxyl group and O-demethylation followed by glucuronide conjugation at either phenolic hydroxyl groups. Minor pathways involve sulfate conjugation of formoterol and deformylation followed by sulfate conjugation. The most prominent pathway involves direct conjugation at the phenolic hydroxyl group. The second major pathway involves O-demethylation followed by conjugation at the phenolic 2'-hydroxyl group. Four cytochrome P450 isozymes (CYP2D6, CYP2C19, CYP2C9 and CYP2A6) are involved in the O-demethylation of formoterol.
Route of elimination:	Following inhalation of a 12 mcg or 24 mcg dose by 16 patients with asthma, about 10% and 15%-18% of the total dose was excreted in the urine as unchanged formoterol and direct conjugates of formoterol, respectively.
Half Life:	10 hours
Clearance:	Renal cl=150 mL/min [Healty subjects receiving oral administration of 80 mcg]
Toxicity:	An overdosage is likely to lead to effects that are typical of ß2-adrenergic stimulants: nausea, vomiting, headache, tremor, somnolence, palpitations, tachycardia, ventricular arrhythmias, metabolic acidosis, hypokalemia, hyperglycemia.
Affected organisms:	Humans and other mammals

Interactions

Drug interaction:

Bisoprolol	Antagonism
Labetalol	Antagonism
Penbutolol	Antagonism
Bevantolol	Antagonism
Sotalol	Antagonism

Targets

Beta-2 adrenergic receptor

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 30-fold greater affinity than it does norepinephrine

UniProt ID:

P07550

Gene:

ADRB2

Actions:

agonist

References:

Handley DA, Senanayake CH, Dutczak W, Benovic JL, Walle T, Penn RB, Wilkinson HS, Tanoury GJ, Andersson RG, Johansson F, Morley J: Biological actions of formoterol isomers. Pulm Pharmacol Ther. 2002;15(2):135-45.
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Scola AM, Chong LK, Suvarna SK, Chess-Williams R, Peachell PT: Desensitisation of mast cell beta2-adrenoceptor-mediated responses by salmeterol and formoterol. Br J Pharmacol. 2004 Jan;141(1):163-71. Epub 2003 Dec 8.
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Ryall JG, Sillence MN, Lynch GS: Systemic administration of beta2-adrenoceptor agonists, formoterol and salmeterol, elicit skeletal muscle hypertrophy in rats at micromolar doses. Br J Pharmacol. 2006 Mar;147(6):587-95.
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Lofdahl CG, Svedmyr N: Formoterol fumarate, a new beta 2-adrenoceptor agonist. Acute studies of selectivity and duration of effect after inhaled and oral administration. Allergy. 1989 May;44(4):264-71.
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Kompa AR, Molenaar P, Summers RJ: Beta-adrenoceptor regulation and functional responses in the guinea-pig following chronic administration of the long-acting beta 2-adrenoceptor agonist formoterol. Naunyn Schmiedebergs Arch Pharmacol. 1995 Jun;351(6):576-88.
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Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5.
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Bartow RA, Brogden RN: Formoterol. An update of its pharmacological properties and therapeutic efficacy in the management of asthma. Drugs. 1998 Feb;55(2):303-22.
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Cheer SM, Scott LJ: Formoterol: a review of its use in chronic obstructive pulmonary disease. Am J Respir Med. 2002;1(4):285-300.
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Steiropoulos P, Tzouvelekis A, Bouros D: Formoterol in the management of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2008;3(2):205-15.
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Faulds D, Hollingshead LM, Goa KL: Formoterol. A review of its pharmacological properties and therapeutic potential in reversible obstructive airways disease. Drugs. 1991 Jul;42(1):115-37.
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Op't Holt TB: Inhaled beta agonists. Respir Care. 2007 Jul;52(7):820-32.
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Enzymes