New clinical evidence of silodosin, an α_1A selective adrenoceptor antagonist, in the treatment for lower urinary tract symptoms

Abstract

Abbreviations & Acronyms a1-AR = a1-adrenoceptor a1A-AR = a1A-adrenoceptor AE = adverse effects BOO = bladder outlet obstruction BOOI = bladder outlet obstruction index BPH = benign prostatic hyperplasia CI = confidence interval CP/CPPS = chronic prostatitis/chronic pelvic pain syndrome DE = disorders of ejaculation GRA = global response assessment HR-QOL = health-related quality of life IPSS = International Prostate Symptom Score ITT = intention to treat LOCF = last observation carried forward LUTS = lower urinary tract symptoms LUTS/BPH = lower urinary tract symptoms associated with benign prostatic hyperplasia mRNA = messenger ribonucleic acid NIH-CPSI = National Institutes of Health Chronic Prostatitis Symptom Index Pdet•Qmax = detrusor pressure at maximal flow PI = prostate implantation PP = per protocol PVR = post-void residual urine Qmax = maximal flow rate RE = retrograde ejaculation SF-12 = Medical Outcomes Study Short Form 12 SIL + EjD = silodosin-treated group with ejaculation disorder SIL -EjD = silodosin-treated group without ejaculation disorder TEAE = treatment emergent adverse effects. Abstract: Lower urinary tract symptoms associated with benign prostatic hyperplasia are highly prevalent in older men. Pharmacological treatment is the first-line treatment for lower urinary tract symptoms associated with benign prostatic hyperplasia. The first choice in the pharmacological treatment for lower urinary tract symptoms associated with benign prostatic hyperplasia is the a1-adrenoceptor antagonists. Many a1-adrenoceptor antagonists are available in the world. Silodosin is an a1-adrenoceptor antagonist developed by Kissei Pharmaceutical, and has a specific selectivity for the a1A-adrenoceptor subtype. By antagonizing a1A-adrenoceptor in the prostate and urethra, silodosin causes smooth muscle relaxation in the lower urinary tract. As a result of the high affinity for the a1A-adrenoceptor than for the a1B-adrenoceptor, silodosin minimizes the propensity for blood pressure-related adverse effects caused by blockade of a1B-adrenoceptor. The efficacy and safety of silodosin for treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia was first reported by Japanese investigators in 2006. At present, silodosin is used in many countries. In the present review, we summarize the new clinical evidence for lower urinary tract symptoms associated with benign prostatic hyperplasia and introduce the data supporting the new clinical indications of silodosin.Key words: a1A adrenergic receptor subtypes, a1-adrenoceptor antagonists, benign prostatic hyperplasia (BPH), lower urinary tract symptoms (LUTS), silodosin.

Silodosin versus naftopidil in Japanese patients with lower urinary tract symptoms associated with benign prostatic hyperplasia: A randomized multicenter study

“…These adverse reactions were considered attributable to the pharmacological actions of these α 1 ‐receptor blockers themselves. In concordance with this observation, the previous study also showed more frequent occurrence of ejaculation disorder in patients treated with silodosin (which has a very high affinity to the α 1A receptor) than in untreated patients; however, the ages of the patients enrolled in the present study were not in the range where their sexual function was of concern.…”

Six‐year follow up of silodosin monotherapy for the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia: What are the factors for continuation or withdrawal?

“…BPH is a common enlargement of the prostate gland that can lead to bladder outlet obstruction, LUTS and impaired quality of life. BPH is present in 50% of men aged older than 50 years, and in approximately 90% of those over the age of 80 years . BPH is a progressive condition.…”

Investigation of ejaculatory disorder by silodosin in the treatment of prostatic hyperplasia

“…The affinity of tamuslosin hydrochloride to α1A receptor is comparatively high while naftopidil is characterized to have comparatively high affinity to α1D receptor subtype [3,4]. On the other hand, silodosin acts on α1A receptor in a very specific manner [5]. The practical clinical application of silodosin started in Japan in 2006.…”