Background:

Silodosin (Rapaflo; KMD-3213) is an α1-adrenoceptor antagonist with high uroselectivity; In treatment of dysuria.IC50 Value:Target: Adrenergic Receptorin vitro: Silodosin potently inhibited 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 had 583- and 56-fold lower potency at the alpha 1b- and alpha 1d-ARs, respectively. Silodosin inhibited 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.in vivo: Using pharmacologically well characterized native rat tissues [submaxillary gland (alpha 1A-AR-expressing tissue), liver (alpha 1B-AR-expressing tissue), and heart (mixed alpha 1A- and alpha 1B-AR-expressing tissue)], binding studies showed that inhibition curves for Silodosin in submaxillary gland and liver best fit a one-site model (with Ki values of 0.15 and 16 nM, respectively), whereas Silodosin had high and low affinity sites in heart membranes. Chloroethylclonidine treatment of rat heart membranes completely eliminated the low affinity sites for Silodosin. Furthermore, in human liver and prostate Silodosin could identify high and low affinity sites, the Ki values of which corresponded well to those for the cloned human alpha 1a- and alpha 1b-ARs, respectively. Moreover, the affinity of Silodosin was found to be approximately 10-fold higher at the cloned human alpha 1a-AR than at the cloned rat alpha 1a-AR.v

参考文献:
[1]. Kobayashi, Shinya; Tomiyama, Yoshitaka; Effects of silodosin and tamsulosin on the urethra and cardiovascular system in young and old dogs with benign prostatic hyperplasia.European Journal of Pharmacology (2009), 613(1-3), 135-140.
[2]. Tatemichi, Satoshi; Tomiyama, Yoshitaka; Maruyama, Itaru; Uroselectivity in male dogs of silodosin (KMD-3213), a novel drug for the obstructive component of benign prostatic hyperplasia.Neurourology and Urodynamics (2006), 25(7), 792-794.
[3]. Osman NI, Chapple CR, Cruz F, Desgrandchamps F, Llorente C, Montorsi F.Silodosin : a new subtype selective alpha-1 antagonist for the treatment of lower urinary tract symptoms in patients with benign prostatic hyperplasia.Expert Opin Pharmacother. 2012 Oct;13(14):2085-96. Epub 2012 Aug 28.
[4]. Cui Y, Zong H, Zhang Y.The efficacy and safety of silodosin in treating BPH: a systematic review and meta-analysis.Int Urol Nephrol. 2012 Aug 24.
[5]. Goseki T, Ishikawa H, Ogasawara S, Mashimo K, Nemoto N, Taguchi Y, Yago K, Shimizu K.Effects of tamsulosin and silodosin on isolated albino and pigmented rabbit iris dilators: Possible mechanism of intraoperative floppy-iris syndrome.J Cataract Refract Surg. 2012 Sep;38(9):1643-9. Epub 2012 Jul 11.