Dobutamine

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.

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.

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.

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.

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. 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.

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, (1973).
 * J. Mills, R. R. Tuttle, (1976).