ABSTRACT

The amino acid alkaloids are active competitive α-adrenoceptor antagonists with a long duration of action. The non-selective antagonist, phentolamine, increases basal and glucose-stimulated insulin levels in man. Unlike the α-adrenoceptor antagonists, the β-adrenoceptor antagonists show a very close structural similarity to their agonist counterparts. Antagonists of β-adrenoceptors have wide therapeutic application in the management of hypertension, myocardial infarction, angina and cardiac arrhythmias, in addition to other non-cardiovascular uses. The first α-adrenoceptor antagonist was the mixture of alkaloids extracted from ergot which is a product of Claviceps purpurea, a fungal contaminant of rye grain. Among the α-adrenoceptor blockers, the β-haloalkylamines are irreversible antagonists which form covalent bonds with the receptor by alkylation. Prazosin is a quinazoline and was the first selective α1-adrenoceptor antagonist to be introduced. Dihydroergocryptine has been employed in early radioligand binding studies of α1-adrenoceptors, with prazosin used as the unlabelled ligand.