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.