Silodosin in the treatment of benign prostatic hyperplasia

Abstract

Benign prostatic hyperplasia (BPH)-associated lower urinary tract symptoms (LUTS) are highly prevalent in older men. Medical therapy is the first-line treatment for LUTS due to BPH. Alpha-adrenergic receptor blockers remain one of the mainstays in the treatment of male LUTS and clinical BPH. They exhibit early onset of efficacy with regard to both symptoms and flow rate improvement, and this is clearly demonstrated in placebo-controlled trials with extensions out to five years. These agents have been shown to prevent symptomatic progression of the disease. The aim of this article is to offer a critical review of the current literature on silodosin, formerly known as KMD-3213, a novel alpha-blocker with unprecedented selectivity for α1A-adrenergic receptors, as compared with both α1B- and α1D -adrenoceptors, exceeding the selectivity of all currently used α1-blockers, and with clinically promising effects.

New medical treatments for lower urinary tract symptoms due to benign prostatic hyperplasia and future perspectives

“…Non-selective α1-antagonists act on the dynamic component of BPH, counteracting smooth muscle contraction in the prostate, which is augmented in BPH, with a consequent increase in urinary flow, reduction of LUTS and improvement in QoL [ 11 , 12 ]. A recent metanalysis has demonstrated the reduction of bladder outlet obstruction index of −30.45 for silodosin, effect which was higher than all other available α1-antagonists [ 13 ]. However, due to their concurrent action on α1 B -receptors, their use is associated with vascular AE, notably orthostatic hypotension, headaches and dizziness [ 8 ].…”

α1-Blockers in Men with Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Obstruction: Is Silodosin Different?

“…In BPH tissue, therefore, α 1 -AR is by far the predominant subtype, with little expression of α 1D and virtually no expression of α 1B receptors. α 1A -AR subtype also regulates contraction of the smooth muscle in the bladder base and neck, urethra, seminal vesicles, and vas deferens [8]. The α 1B -AR is the predominant subtype in the peripheral vasculature of men aged 65 years or older and it regulates contraction of arterial blood vessels in response to postural redistribution of blood volume.…”

“…Pharmacologic uroselectivity of ABs is defined on the basis of binding affinities for the three α 1 -AR subtypes [3]. Quinazolone first-generation ABs such as terazosin and doxazosin and alfuzosin are non-subtype-selective drugs with similar affinity for all α 1 -ARs [8, 9]. Selective ABs, in contrast, have greater and more favorable interactions with one receptor subtype versus others.…”

“…Tamsulosin, naftopidil, and silodosin are considered subtype selective. Tamsulosin preferentially blocks α 1A -AR and α 1D -AR [8]. Tamsulosin is 15- and 3-fold more selective for the α 1A -AR subtype than for the α 1B -AR and α 1D -AR subtypes [10, 11].…”

“…It has a three times greater affinity for the α 1D -AR subtype than for the α 1A -AR subtype. Silodosin is highly selective for α 1A -AR, with a 162-fold greater affinity than for α 1B -AR and about a 50-fold greater affinity than for α 1D -AR [8, 11]. …”