A Concise and Useful Guide to Understand How Alpha1 Adrenoceptor Antagonists Work

Abstract

Adrenoceptors are the receptors for the catecholamines, adrenaline and noradrenaline. They are divided in α (α1 and α2) and β (β1, β2 and β3). α1-Adrenoceptors are subdivided in α1A, α1B and α1D. Most tissues express mixtures of α1-adrenoceptors subtypes, which appear to coexist in different densities and ratios, and in most cases their responses are probably due to the activation of more than one type. The three subtypes of α1-adrenoceptors are G-protein-coupled receptors (GPCR), specifically coupled to Gq/11. Additionally, the activation of these receptors may activate other signaling pathways or different components of these pathways, which leads to a great variety of possible cellular effects. The first clinically used α1 antagonist was Prazosin, for Systemic Arterial Hypertension (SAH). It was followed by its congeners, Terazosin and Doxazosin. Nowadays, there are many classes of α-adrenergic antagonists with different selectivity profiles. In addition to SAH, the α1-adrenoceptors are used for the treatment of Benign Prostatic Hyperplasia (BPH) and urolithiasis. This antagonism may be part of the mechanism of action of tricyclic antidepressants. Moreover, the activation of these receptors may lead to adverse effects such as orthostatic hypotension, similar to what happens with the antidepressants and with some antipsychotic. Structure-activity relationships can explain, in part, how antagonists work and how selective they can be for each one of the subtypes. However, it is necessary to develop new molecules which antagonize the α1-adrenoceptors or make chemical modifications in these molecules to improve the selectivity, pharmacokinetic profile and/or reduce the adverse effects of known drugs.

Elsholtzia ciliata Essential Oil Exhibits a Smooth Muscle Relaxant Effect

“…Some furan-containing compounds have therapeutic applications in systematic diseases. For example, prazosin, an α 1 -adrenergic receptor antagonist, medication prescribed for the treatment of several diseases including hypertension and benign prostatic hyperplasia [10], contains a furan ring. Furosemide, an inhibitor of Na + -K + -2Cl − cotransporter-2, a potent diuretic agent applied to decrease extracellular fluid volume expansion in heart and kidney disease [11], also features this ring in its molecular design.…”