α₁-Adrenoceptors as potential therapeutic targets

Abstract

Adrenergic receptors belong to the seven transmembrane spanning, G-protein-coupled receptor super family, which mediate the actions of the endogenous catecholamines, adrenaline and noradrenaline (also known as epinephrine and norepinephrine). Adrenergic receptors are involved in several disease states such as hypertension, cardiac dysfunction, diabetes, glaucoma, depression, impotence and lower urinary tract disorders. This makes adrenergic receptors a valuable therapeutic target for the treatment of various disorders. Adrenergic receptors are broadly categorised into α₁-,α₂- and β-subtypes. Of these, α₁-adrenoceptors, located in both central and peripheral nervous systems, are of great therapeutic relevance because of their important role in the contraction of smooth muscle tissue, especially in the cardiovascular system and lower urinary tract. The α₁-adrenoceptor subtype has been further divided into α_1A, α_1B and α_1D and ligands acting at these subtypes have therapeutic potential in the treatment of hypertension, stress urinary incontinence (SUI), benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). This review summarises the patent literature from 2001 to early 2005 on the development of selective ligands of the α₁-adrenoceptor and its subtypes.

Keywords::

• α₁-adrenoceptor
• α₁-adrenoceptor antagonist
• α₁-AR agonist
• benign prostatic hyperplasia
• hypertension
• lower urinary tract symptoms
• selectivity