Silodosin

A highly potent, uroselective α1a-adrenoceptor antagonist with Ki of 36 pM; displays 583- and 56-fold lower potency against α1b and α1d respectors, respectively; inhibits norepinephrine-induced increases intracellular Ca2+ concentrations in CHO cells with IC50 of 0.32 nM; inhibits intraurethral pressure (IUP) response in vivo.Other Indication Approved (In Vitro) :Silodosin (KAD 3213; KMD 3213) inhibits norepinephrine-induced increases in intracellular Ca2+ concentrations in alpha 1a-AR-expressing Chinese hamster ovary cells with an IC50 of 0.32 nM but had a much weaker inhibitory effect on the alpha 1b- and alpha 1d-ARs.Silodosin potently inhibits 2-[2- (4-hydroxy-3-[125I]iodophenyl) ethylaminomethyl]-alpha-tetralone binding to the cloned human alpha 1a-AR, with a Ki value of 0.036 nM, but has 583- and 56-fold lower potency at the alpha 1b- and alpha 1d-ARs, respectively.Silodosin (0-10 μM; 24 hours) decreases ELK1 gene expression as a dose-dependent manner in all the bladder cancer cell lines.Silodosin (0-10 μM; 24 hours) decreases ELK1 protein expression as a as a dose-dependent manner.Silodosin (0-10 μM; 96 hours) insignificantly changes cell viability of AR-positive UMUC3 or TCCSUP cultured in an androgen-depleted condition or that of AR-negative 647V. In contrast, silodosin reduced the growth of UMUC3 cells cultured with normal FBS containing androgens (58% decrease at 10 μM) . (In Vivo) :Silodosin (intravenous injection; 0.1-0.3mg/kg) reduces the obstruction-induced increases in MinP by 27.7 % (0.1 mg/kg) and 20.8 % (0.3 mg/kg) . It improves detrusor overactivity and reduces the grade of obstruction, and thus may be effective for both storage and voiding dysfunction for the treatment of LUTS/BPH.