alpha- and beta-Adrenoceptor activities of norepinephrine analogues in isolated tissues of the rat.

A range of norepinephrine analogues has been studied in rat tracheal, atrial, and aortic preparations. Isopropyl appeared to be the most favorable N-substituent for agonist action on tracheal adrenoceptors, whereas hydroxyphenylisopropyl gave highest activity on atrial adrenoceptors. Selectivity for the beta 2-adrenoceptor was improved with tertiary branching at the gamma-carbon and further increased by aromatic substitution with resorcinol or saligenin. Alpha-Adrenoceptor properties were substantially modified by N-substitution, whereas aromatic substitution was an important factor in determining beta-adrenoceptor agonist or antagonist activity at the beta-adrenoceptor. The data were consistent with norepinephrine analogues having multiple sites of attachment to the receptor membrane influencing receptor potency and selectivity. The data also suggest that compounds of this type can have actions on both alpha- and beta-adrenoceptors.