Alpha1 (α1)-adrenergic receptor antagonists, or alpha-blockers, are the most widely used medical therapy for the treatment of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH).1
How Alpha-blockers Work
In the treatment of BPH, these agents work by binding to α1-adrenergic receptors in the bladder neck and prostate, and blocking the neurotransmitter norepinephrine from binding to the receptor.2 This action relaxes the smooth muscle tissue of the bladder and prostate, improving urine flow and reducing BPH symptoms.3
Alpha-adrenergic Receptor Function
The activity of alpha-blockers in the treatment of BPH and their side effect profiles are thought to depend on the degree of selectivity for one or more of the three α1 receptor subtypes: α1A, α1B, and α1D. In general, prostate smooth muscle contraction is regulated by α1A-adrenergic receptors,4 whereas contraction of the smooth muscle of blood vessels is regulated primarily by α1B receptor subtypes.5 The role of α1D receptors is unclear but they are thought to play a role in bladder symptoms (mediated through C-fiber afferent activity), and nasal secretions.2, 6-9
A Selective Profile
In theory, an alpha-blocker that selectively inhibits the α1A receptor subtype would—at therapeutic doses—primarily have effects on contractile response of human prostate tissue without significantly affecting contraction of the vascular smooth muscle or other functions. Clinically, this would mean an alpha-blocker with high efficacy in relieving the symptoms of BPH, but few side effects related to contraction of vascular smooth muscle (eg, blood pressure changes, orthostatic hypotension).