For all other endpoints, the effectiveness of monotherapy was similar and combination therapy was superior to the monotherapy groups.

Table 3 MTOPS Versus CombAT Table 4 Outcomes From the CombAT Study New α-Blockers The evolution of α-blockers for the treatment of clinical BPH has involved the development of subtype-selective αwww.selleckchem.com/products/Nilotinib.html -antagonists and novel formulations that ultimately allow for Inhibitors,research,lifescience,medical a single, daily-dose administration without the requirement for dose titration.10 There are three subtypes of the α1A,α1B, and α1D. The α1A- and α1B-adrenoceptor are predominant in the prostate and vasculature, respectively, whereas the α1D-adrenoceptor is present in the bladder and nerve junctions (Figure 6).16 Of all α-blockers, only silodosin exhibits any degree of α-adrenoceptor subtype selectivity that can be leveraged in the clinical

setting. Silodosin exhibits very high selectivity for α1A versus α1B and modest selectivity for α1A versus α1D. If efficacy is mediated by α1A and α1D and toxicity by α1B, then silodosin has the potential for unique Inhibitors,research,lifescience,medical clinical properties. The clinical data suggest that silodosin is essentially devoid of cardiovascular side effects.17,18 On the other hand, the incidence of ejaculatory Inhibitors,research,lifescience,medical dysfunction exceeds all other α-blockers.17 Interestingly, the subset of men experiencing ejaculatory dysfunction experiences the greatest efficacy (Figure 7).19 Therefore, the utility of silodosin in the treatment of BPH must balance maximizing effectiveness, limiting cardiovascular side effects, and preventing ejaculatory dysfunction. Figure 6 New concepts in drug development of α-blockers. AR, androgen receptor; Inhibitors,research,lifescience,medical BOO, bladder outlet obstruction; LUTS, Inhibitors,research,lifescience,medical lower urinary tract symptoms. Reproduced with permission

from Lepor H, Rev Urol. 2009;11 (suppl 1):S9–S13. Figure 7 Silodosin post hoc responder analysis by selleckchem ejaculation status. Based on patient subanalysis. IPSS, International Prostate Symptom Score; RE, retrograde ejaculation. Data on file, Watson Pharmaceuticals, Inc., Corona, CA. Novel Nonsurgical Treatment of BPH The mechanism by which BPH causes LUTS is still poorly understood. In men with BPH, there is only a weak correlation between severity of LUTS and BOO.20 There is also a poor correlation between the improvement in LUTS and BOO in men following medical and surgical therapy of Brefeldin_A BPH.20 Thus, although the concept that BPE causes BOO leading to LUTS was the foundation for developing α-blocker and 5-ARI therapy, this is an oversimplification. There is little doubt that the prostate plays a central role in LUTS, because the majority of men experience dramatic improvement in symptoms following a transurethral or radical prostatectomy. 21 Therefore, the development of novel nonsurgical therapies does not necessarily need to target relieving BOO exclusively.