Dobutamine, (±) 4-[2(4′-hydroxyphenyl)-1-methylpropyl]-3,4-dihydroxyphenylethylamine (11.1.31), differs significantly from all of the presented drugs in terms
of structure, the main difference being the absence of a hydroxyl group at the β-carbon
atom of the phenylethylamine moiety of classic sympathomimetics. The second considerable difference from the examined drugs is the presence of p-hydroxyphenyl-iso-butylamine group as a terminal amine substituent.
용도
Dobutamine is used in situations where, during severe cardiac decompensation, it is necessary to temporarily strengthen contractions of the myocardium, and in particular during
decompensation of cardiac activity associated with surgical intervention on the heart or in
organic diseases.
일반 설명
Dobutamine (Dobutex) is a sympathomimeticdrug that is a β1-adrenergic agonist with α1-activity.It is primarily used in cases of cardiogenic shock, which resultfrom its β1-inotropic effects, which increase heart contractilityand cardiac output. The drug is dispensed and administeredas a racemic mixture consisting of both (+) and(-) isomers. The (+) isomer is a potent 1-agonist, whereasthe (-) isomer is an α1-agonist.
Clinical Use
Among the most promising β1 adrenergic agonists are those derived from dopamine, the endogenous
precursor to norepinephrine. Dopamine itself is a potent stimulator of the β1-receptors, but it results
in many of the undesirable side effects described in Chapter 13. The new analogs of dopamine that
have been developed retain the potent inotropic effect but possess fewer effects on heart rate,
vascular tone, and arrhythmias. Dobutamine is a prime representative of this group of agents. Dobutamine is a potent β1-adrenergic agonist on the myocardium with beneficial
effects, the composite of a variety of actions on the heart and the peripheral vasculature.
Dobutamine is active only by the intravenous route because of its rapid first-pass metabolism via
COMT (catechal-O-methyl transferase). Therefore, its use is limited to critical care situations.
Nonetheless, its parenteral success has led to the search and development of orally active drugs.
One of the major limitations associated with β1-agonists is the phenomenon of myocardial β-receptor
desensitization. This lowered responsiveness (desensitization) of the receptors appears to be due to
a decrease in the number of β1-receptors and partial uncoupling of the receptors from adenylate
cyclase.
