6.11:
Adrenergic Antagonists: Chemistry and Classification of ɑ-Receptor Blockers
Adrenergic antagonists, or sympatholytics, bind to adrenoceptors to prevent receptor activation by catecholamines or other agonists.
They can be classified as ɑ or β adrenergic blockers based on their affinities for adrenoceptors.
α-blockers bind to the ɑ1 and ɑ2 subtypes. They are either nonselective or selective, based on their specificity.
Nonselective α-blockers, such as phenoxybenzamine and phentolamine], contain haloalkylamine and imidazoline moieties, respectively.
Selective α1-blockers feature quinazoline and piperazine rings along with an acyl group.
The optimal activity of these compounds depends on the 4-amino group and the nature of the acyl group, which yields prazosin and its analogs.
Selective α2-blockers, such as yohimbine, belong to the indole alkylamines category.
In conclusion, the α-blockers exhibit structural diversity and bear little resemblance to their agonist counterparts. Nevertheless, they effectively antagonize the actions of agonists on the adrenoceptors.
6.11:
Adrenergic Antagonists: Chemistry and Classification of ɑ-Receptor Blockers
Adrenergic antagonists, or sympatholytics, inhibit adrenoceptor activation driven by catecholamines or agonists. Based on their adrenoceptor specificity, adrenergic blockers can be categorized into two primary groups: α-adrenergic blockers (α-blockers) and β-adrenergic blockers (β-blockers). α-blockers interact with α1 and α2 subtypes of α-adrenoceptors.
Nonselective α-blockers: Nonselective α-blockers contain haloalkylamine or imidazoline moieties. Phenoxybenzamine, with a haloalkylamine structure, and phentolamine, featuring an imidazoline ring, are nonselective α-blockers.
Selective α1 blockers: Selective α1 blockers possess quinazoline and piperazine rings with an acyl group. Prazosin, a highly selective α1 blocker, exhibits optimal efficacy due to the presence of the 4-amino group and the specific characteristics of the acyl group. Various analogs with alternative heterocyclic rings can substitute the piperazine ring in selective α1 blockers while maintaining comparable pharmacological properties.
Selective α2 blockers: Selective α2 blockers, such as yohimbine, have an indole alkylamine structure. Yohimbine is found in the bark of Pausinystalia yohimbe and Rauwolfia roots. It selectively targets α2 receptors predominantly located on presynaptic nerve terminals, modulating norepinephrine release and amplifying sympathetic outflow.
Overall, α-adrenergic blockers encompass a diverse range of molecules that differ structurally from adrenergic agonists. Through α-adrenoceptor inhibition, they modulate the sympathetic nervous system.