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UROSCAN
Year : 2007  |  Volume : 23  |  Issue : 2  |  Page : 215-216
 

Search for new α1a-adrenoceptor-selective antagonist for treating lower urinary tract symptoms associated with benign prostatic hyperplasia


Department of Urology and Renal Transplant, SGPGIMS, Lucknow, India

Correspondence Address:
Naval Khurana
Department of Urology and Renal Transplant, SGPGIMS, Lucknow
India
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Source of Support: None, Conflict of Interest: None


PMID: 19675810

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How to cite this article:
Khurana N, Srivastava A. Search for new α1a-adrenoceptor-selective antagonist for treating lower urinary tract symptoms associated with benign prostatic hyperplasia. Indian J Urol 2007;23:215-6

How to cite this URL:
Khurana N, Srivastava A. Search for new α1a-adrenoceptor-selective antagonist for treating lower urinary tract symptoms associated with benign prostatic hyperplasia. Indian J Urol [serial online] 2007 [cited 2019 Jul 16];23:215-6. Available from: http://www.indianjurol.com/text.asp?2007/23/2/215/32084

Kawabe K, Yoshida M, Homma Y: The Silodosin Clinical Study Group. Silodosin, a new alpha-adrenoceptor-selective antagonist for treating benign prostatic hyperplasia: Results of a Phase III randomized, placebo-controlled, double-blind study in Japanese men. BJU Int 2006;98:1019-24.



   Summary Top


This phase III randomized, multicentric, double-blind, placebo-controlled, study[1] in Japanese men has shown the clinical efficacy of silodosin, a new a 1A -adrenoceptor-selective antagonist for treating lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). The change in the total International prostatic symptom score (IPSS) from baseline in the silodosin, tamsulosin and placebo groups was -8.3, -6.8 and -5.3, respectively. There was a significant decrease in the IPSS vs. placebo in the silodosin group from one week. In the early-stage comparison, silodosin showed a significant decrease in IPSS vs. tamsulosin at two weeks. The change in QoL from baseline was -1.7, -1.4 and -1.1 in the silodosin, tamsulosin and placebo groups, respectively. Silodosin showed a significant improvement in the QoL score vs. placebo. In the subgroup of patients with severe symptoms (IPSS ≥ 20) silodosin also gave a significantly better improvement than placebo (-12.4 vs. -8.7). The incidence rates of adverse events and drug-related adverse events were, respectively, 88.6%, 82.3% and 71.6% and 69.7%, 47.4% and 36.4%, respectively. The most common adverse event in the silodosin group was abnormal ejaculation, which occurred more often in the silodosin than in the tamsulosin group (22.3% vs. 1.6%).


   Comments Top


It is well established that all α 1 -adrenoceptor blockers currently recommended for treating LUTS (alfuzosin, doxazosin, tamsulosin, terazosin) have equal clinical effectiveness, producing a mean 4-6 point improvement in the IPSS.[2] However, they differ in side-effect profiles due to difference in the affinity of these blockers on α-adrenoceptor. In the AUA meta-analysis,[2] while the four α1 -adrenoceptor blockers showed incidences of decreased libido (1-3%) and erectile dysfunction (3-5%) closely similar to placebo (3 and 4% respectively), tamsulosin was associated with higher incidence of ejaculatory dysfunction (10%) than other α 1 -adrenoceptor blockers (0-1%) and placebo (1%).The incidence of ejaculatory dysfunction with tamsulosin not only increases with dose[3] but also increases with time.[4]

To date several α 1 -adrenoceptor blockers with very high α 1 -adrenoceptor selectivity have been developed, but their efficacy and safety profiles have not been confirmed clinically in patients with BPH. This study[1] has shown better efficacy of silodosin over tamsulosin (0.2 mg) with more incidence of ejaculatory dysfunction (22.3% vs. 1.6%) but only 2.9% discontinuation rate. Better efficacy might elicit improvement even in patients who could be candidates for surgical therapy but at the cost of more side-effects. Better effect of silodosin could be due to high selectivity for α 1a -adrenoceptor or due to suboptimal does of tamsulosin (0.2 mg) even in the apparently 'α blocker- ultrasensitive' Japanese population.

When treating LUTS associated with BPH it is necessary to focus not just on symptoms generated by bladder outlet obstruction (voiding symptoms mediated by α1a-adrenoceptor) but also on symptoms generated by bladder dysfunction (storage symptoms mediated by α1d-adrenoceptor). Both silodosin and tamsulosin have more affinity for α1a -adrenoceptor hence are more effective in relieving voiding symptoms. Drugs alleviating both storage and voiding symptoms have been discovered like naftopidil which has high affinity for α1d[5] in comparison to α1a-adrenoceptor. Naftopidil has been found more effective than tamsulosin in alleviating storage symptoms with equal efficacy on voiding symptoms.[6] Hence search for potent and selective α1- adrenoceptor blockers with minimal side-effects for treatment of LUTS associated with BPH is still continuing.

 
   References Top

1.Kawabe K, Yoshida M, Homma Y; Silodosin Clinical Study Group. Silodosin, a new alpha adrenoceptor-selective antagonist for treating benign prostatic hyperplasia: Results of a phase III randomized, placebo-controlled, double-blind study in Japanese men. BJU Int 2006;98:1019-24.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.AUA Practice Guidelines Committee. AUA guideline on management of benign prostatic hyperplasia (2003). Chapter 1: Diagnosis and treatment recommendations. J Urol 2003;170:530-47.  Back to cited text no. 2    
3.Lepor H. Phase III multicenter placebo-controlled study of tamsulosin in benign prostatic hyperplasia. Tamsulosin Investigator Group. Urology 1998;51:892-900.  Back to cited text no. 3    
4.Lepor H. Long-term evaluation of tamsulosin in benign prostatic hyperplasia: Placebo-controlled, double-blind extension of phase III trial. Tamsulosin Investigator Group. Urology 1998;51:901-6.  Back to cited text no. 4    
5.Takei R, lkeqaki I, Shibata K, Tsujimoto G, Asano T. Naftopidil, a novel alpha 1 adrenoreceptor antagonist, displays selective inhibition of canine prostatic pressure and high affinity binding to cloned human alpha 1-adrenoreceptors. Jpn J Phrmacol 1999;79:447-54.   Back to cited text no. 5    
6.Nishino Y, Masue T, Miwa K, Takahashi Y, Ishihara S, Deguchi T. Comparison of the two a1 adrenoreceptor antagonist naftopidil and tamsulosin hydrochloride, in the treatment of lower urinary tract symptoms with benign prostatic hyperplasia: A randomized crossover study. BJU Int 2006;97:747-51.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]




 

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