Dobutamine receptor pharmacology

In vivo, racemic dobutamine increases the inotropic activity of the heart to a much greater extent than it increa.ses chronotropic activity. This pharmacological profile has led to its use in treating congestive heart failure. Since /3 receptors are involved positively in both inotropic and chronotropic effects of the heart, the selective inotropic effect. seen with dobutamine cannot simply be due to its activity at P% receptors. Rather, this effect is the result of a combination of the inotropic effect of (-t- )-dohutamine on Px receptors and that of (-)-dobutamine mediated through 0 receptors. Thus, this is a case where a racemic mixture provides a more desirable pharmacological and therapeutic cITect than would cither enantiomer alone. 

The two isomers of dobutamine have opposing effects at the a, receptor. The + isomer of dobutamine has antagonist activity at the a, receptor, while the isomer has agonist activity. The two isomers are thus dispensed as a racemic mixture, to avoid the pharmacologic variable of alpha-receptor activity. 

The pharmacological effects of dobutamine (see Table 10-1 for structure) result from direct interactions with a and /3 receptors and are complex. The preparation of dobutamine used clinically is a racemate. The (-) isomer of dobutamine is a potent agonist and pressor (+) dobutamine is a potent (Tj antagonist that can block the effects of (-) dobutamine. Both isomers are full agonists at /3 receptors, but the (-I-) isomer is more potent than the (-) isomer by -tenfold. 

The cardiovascular effects of racemic dobutamine are a composite of the pharmacological properties of the (—) and (-V) stereoisomers. Dobutamine has relatively more prominent inotropic than chronotropic effects, compared to isoproterenol. This useful selectivity may arise because peripheral resistance is relatively unchanged due to a counterbalancing ofa receptor-mediated vasoconstriction and receptor-mediated vasodilation. Alternatively, cardiac receptors may contribute to the inotropic effect. At equivalent inotropic doses, dobutamine enfumces automatic-ity of the sinus node to a lesser extent than does isoproterenol however, enhancement of AV and intraventricular conduction is similar for both drugs. 

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