New clinical evidence of silodosin, an α(1A) selective adrenoceptor antagonist, in the treatment for lower urinary tract symptoms.

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 α(1) -adrenoceptor antagonists. Many α(1) -adrenoceptor antagonists are available in the world. Silodosin is an α(1) -adrenoceptor antagonist developed by Kissei Pharmaceutical, and has a specific selectivity for the α(1A-) adrenoceptor subtype. By antagonizing α(1A) -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 α(1A) -adrenoceptor than for the α(1B) -adrenoceptor, silodosin minimizes the propensity for blood pressure-related adverse effects caused by blockade of α(1B) -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.

Effects of Chronic Hyperlipidemia on Lower Urinary Tract Function-Bladder Dysfunction in Myocardial Infarction-Prone Watanabe Heritable Hyperlipidemic Rabbits.

To evaluate the effects of chronic hyperlipidemia on bladder function, we examined the functional and histological changes of the bladder in myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHL-MI) rabbits. Two age groups of WHHL-MI rabbits (6-12 months old, young WHHL-MI rabbits; and 20-24 months old, old WHHL-MI rabbits group) and the sex- and age-matched control rabbits were prepared. Bladder functions were evaluated using frequency volume charts and cystometrograms, and functional experiments using isolated bladder specimens. Histological studies of bladder were performed with HE staining and immunohistochemical staining with mouse monoclonal S-100 protein antibodies and sheep polyclonal calcitonin gene-related peptide (CGRP) antibodies. In cystometrograms, it has been demonstrated that WHHL-MI rabbits showed significantly shorter micturition interval, smaller voided volume with non-voiding contractions compared to control. There was no significant difference in voiding pressure between young WHHL-MI and control rabbits. However, old WHHL-MI rabbits showed a lower voiding pressure than control rabbits. The functional experiments revealed that carbachol- and electrical field stimulation (EFS)-induced contractile responses of isolated bladder strips were significantly increased in young WHHL-MI rabbits than in control rabbits. However, in the bladder strips of old WHHL-MI rabbits, decreased responses to carbachol and EFS were observed. In WHHL-MI rabbits, bladder urothelium became thinner, smooth muscle area decreased and connective tissue area increased gradually with aging. A significant decrease in S-100 protein-positive neurons, and an increased number of CGRP-positive neurons were observed in both young and old WHHL-MI rabbits. The data demonstrated that there were differences in bladder dysfunction between young and old WHHL-MI rabbits. Old WHHL-MI rabbits showed detrusor hyperactivity with impaired contraction. This study may demonstrate the developmental mechanism of bladder dysfunction in chronic hyperlipidemia.

Safety and efficacy of silodosin for the treatment of benign prostatic hyperplasia.

Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) are highly prevalent in older men. Medical therapy is the first-line treatment for LUTS associated with BPH. Mainstays in the treatment of male LUTS and clinical BPH are the α(1)-adrenergic receptor antagonists. Silodosin is a new α(1)-adrenergic receptor antagonist that is selective for the α(1A)-adrenergic receptor. By antagonizing α(1A)-adrenergic receptors in the prostate and urethra, silodosin causes smooth muscle relaxation in the lower urinary tract. Since silodosin has greater affinity for the α(1A)-adrenergic receptor than for the α(1B)-adrenergic receptor, it minimizes the propensity for blood pressure-related adverse effects caused by α(1B)-adrenergic receptor blockade. In the clinical studies, patients receiving silodosin at a total daily dose of 8 mg exhibited significant improvements in the International Prostate Symptom Score and maximum urinary flow rate compared with those receiving placebo. Silodosin showed early onset of efficacy for both voiding and storage symptoms. Furthermore, long-term safety of silodosin was also demonstrated. Retrograde or abnormal ejaculation was the most commonly reported adverse effect. The incidence of orthostatic hypotension was low. In conclusion, silodosin, a novel selective α(1A)-adrenergic receptor antagonist, was effective in general and without obtrusive side effects. This review provides clear evidence in support of the clinical usefulness of silodosin in the treatment of LUTS associated with BPH.