Dobutamine

Dobutamine

Systematic (IUPAC) name
(RS)-4-(2-{[4-(4-hydroxyphenyl)butan-2-yl]amino}ethyl)benzene-1,2-diol
Clinical data
AHFS/Drugs.com	monograph
MedlinePlus	a682861
Pregnancy cat.	B
Legal status	?
Routes	Intravenous
Pharmacokinetic data
Half-life	2 minutes
Identifiers
CAS number	34368-04-2 Y
ATC code	C01CA07
PubChem	CID 36811
IUPHAR ligand	535
DrugBank	APRD00122
ChemSpider	33786 Y
UNII	0WR771DJXV Y
KEGG	D03879 Y
ChEBI	CHEBI:4670 Y
ChEMBL	CHEMBL926 Y
Synonyms	Dobutrex, Inotrex
Chemical data
Formula	C18H23NO3
Mol. mass	301.38 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C18H23NO3/c1-13(2-3-14-4-7-16(20)8-5-14)19-11-10-15-6-9-17(21)18(22)12-15/h4-9,12-13,19-22H,2-3,10-11H2,1H3 Y Key:JRWZLRBJNMZMFE-UHFFFAOYSA-N Y
N(what is this?)  (verify)

Dobutamine is a sympathomimetic drug used in the treatment of heart failure and cardiogenic shock. Its primary mechanism is direct stimulation of β₁ receptors of the sympathetic nervous system. Dobutamine was developed by a laboratory led by Drs. Ronald Tuttle and Jack Mills at Eli Lilly and Company, as a structural analogue of isoprenaline.^[1]

Clinical uses

Dobutamine is used to treat acute but potentially reversible heart failure, such as which occurs during cardiac surgery or in cases of septic or cardiogenic shock, on the basis of its positive inotropic action.^[2]

Dobutamine can be used in cases of congestive heart failure to increase cardiac output. It is indicated when parenteral therapy is necessary for inotropic support in the short-term treatment of patients with cardiac decompensation due to depressed contractility, which could be the result of either organic heart disease or cardiac surgical procedures. It is not useful in ischemic heart disease because it increases heart rate and thus increases myocardial oxygen demand.

The drug is also commonly used in the hospital setting as a pharmacologic stress testing agent to identify coronary artery disease.

Adverse effects

Primary side effects include those commonly seen for β₁ active sympathomimetics, such as hypertension, angina, arrhythmia, and tachycardia. Used with caution in atrial fibrillation as it has the effect of increasing the atriovenrticular (AV) conduction.^[3]

The most dangerous side effect of dobutamine is increased risk of arrhythmia, including fatal arrhythmias. Studies suggest that while this medication can improve symptoms in chronic CHF, it actually shortens a patient's lifespan.

Pharmacology

Dobutamine is a direct-acting agent whose primary activity results from stimulation of the β₁-adrenoceptors of the heart, increasing contractility and cardiac output. Since it does not act on dopamine receptors to induce the release of norepinephrine (another α₁ agonist), dobutamine is less prone to induce hypertension than is dopamine.

Dobutamine is predominantly a β₁-adrenergic agonist, with weak β₂ activity, and α₁ selective activity, although it is used clinically in cases of cardiogenic shock for its β₁ inotropic effect in increasing heart contractility and cardiac output. Dobutamine is administered as a racemic mixture consisting of both (+) and (−) isomers; the (+) isomer is a potent β₁ agonist and α₁ antagonist, while the (−) isomer is an α₁ agonist.^[4] The administration of the racemate results in the overall β₁ agonism responsible for its activity. (+)-Dobutamine also has mild β₂ agonist activity, which makes it useful as a vasodilator.^[5]

Chemistry

It is synthesized by the reaction of 2-(3,4-dimethoxyphenyl)ethanamine and 1-(4-methoxyphenyl)-3-butanone with a simultaneous reduction of formed imine. The methoxyl-protecting groups of this intermediate are cleaved by hydrogen bromide giving dobutamine.

• R. R. Tuttle, J. Mills, DE 2317710  (1973).
• J. Mills, R. R. Tuttle, U.S. Patent 3,987,200 (1976).

References

1. ^ Tuttle RR, Mills J (January 1975). "Dobutamine: development of a new catecholamine to selectively increase cardiac contractility". Circ Res 36 (1): 185–96. doi:10.1161/01.RES.36.1.185. PMID 234805. http://circres.ahajournals.org/cgi/reprint/36/1/185. 
2. ^ Rang HP, Dale MM, Ritter JM, Flower RJ. Rang and Dale's Pharmacology. 
3. ^ Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 6. ISBN 1-59541-101-1. 
4. ^ Parker K, Brunton L, Goodman LS, Blumenthal D, Buxton I (2008). Goodman & Gilman's manual of pharmacology and therapeutics. McGraw-Hill Medical. pp. 159. ISBN 0-07-144343-6. 
5. ^ Tibayan FA, Chesnutt AN, Folkesson HG, Eandi J, Matthay MA (1997). "Dobutamine increases alveolar liquid clearance in ventilated rats by beta-2 receptor stimulation". Am. J. Respir. Crit. Care Med. 156 (2 Pt 1): 438–44. PMID 9279221. 

[[Category: