Structure-Activity Relationships of Sympathomimetics

Due to its equally high affinity for all a-and p-receptors, epinephrine does not permit selective activation of a particular receptor subtype. Like most catecholamines, it is also unsuitable for oral administration (catechol is a trivial name for o-hydroxyphenol). Norepinephrine differs from epinephrine by its high affinity for a-receptors and low affinity for P2-receptors. In contrast, isoproterenol has high affinity for p-recep-tors, but virtually none for a-receptors (A). 

Knowledge of structure-activity relationships has permitted the synthesis of sympathomimetics that display a high degree of selectivity at adrenoceptor subtypes. 

Absence of one or both aromatic hydroxyl groups is associated with an increase in indirect sympathomimetic activity, denoting the ability of a substance to release norepinephrine from its neuronal stores without exerting an agonist action at the adrenoceptor (p. 88). 

Since structural requirements for high affinity, on the one hand, and oral applicability, on the other, do not match, choosing a sympathomimetic is a matter of compromise. If the high affinity of epinephrine is to be exploited, absorbability from the intestine must be foregone (epinephrine, isoprenaline). If good bioavailability with oral administration is desired, losses in receptor affinity must be accepted (etilefrine). 

1 1 Affinity for a-receptors 1 1 Affinity for p-receptors 1—1 Indirect 1—1 action 1 1 Resistance to degradation 1 1 Absorbability 

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