Disease relevance of Silodosin

• Furthermore, the alpha(1A)-adrenoceptor selective antagonist KMD-3213 would be suitable for improving irritative symptoms in patients with benign prostatic hyperplasia [1].
• These results indicate that KMD-3213 is not likely to induce orthostatic hypotension and would be a useful compound for the treatment of urinary outlet obstruction in patients with benign prostatic hyperplasia [2].

High impact information on Silodosin

• KMD-3213, a novel, potent, alpha 1a-adrenoceptor-selective antagonist: characterization using recombinant human alpha 1-adrenoceptors and native tissues [3].
• Chloroethylclonidine treatment of rat heart membranes completely eliminated the low affinity sites for KMD-3213 [3].
• [3H]-silodosin binding sites also showed high affinity for silodosin and tamsulosin but low sensitivity to BMY 7378 (8-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspiro(4.5)decane-7,9-dione) (Research Biochemicals International) in intact segments and in membrane preparations [4].
• After 4 weeks a pressure flow study was done and the effects of the alpha(1)-adrenoceptor antagonists KMD-3213 silodosin, tamsulosin and prazosin on urodynamics were compared [1].
• Alpha-1 adrenoceptor up-regulation induced by prazosin but not KMD-3213 or reserpine in rats [5].

Chemical compound and disease context of Silodosin

• OBJECTIVE To verify the efficacy and safety of the new alpha(1A)-adrenoceptor-selective antagonist silodosin compared with tamsulosin and placebo in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) [6].

Biological context of Silodosin

• In the present study, we investigated the effects of KMD-3213 on the tilt-induced blood pressure response in anesthetized normotensive rats [2].

Anatomical context of Silodosin

• Comparing these functional affinities with those in the mesenteric artery, only KMD-3213 exhibited substantial tissue selectivity, showing more than 100-fold higher affinity for human prostate than for mesenteric artery [7].
• In the in vitro study, after evaluating the inhibitory effects of silodosin on noradrenaline (NA)-induced contractions in the isolated prostate and isolated carotid artery using the Magnus method, we calculated prostatic selectivity [8].
• In the present study, we characterized the inhibitory effect of KMD-3213 on the phenylephrine (alpha 1-adrenoceptor-selective agonist)-induced contraction of rabbit prostate, rabbit thoracic aorta and rat thoracic aorta to functionally confirm the tissue selectivity of KMD-3213 [9].
• These data suggest that KMD-3213 and JTH-601 exhibit higher affinity to alpha1-adrenoceptors in prostate and submaxillary gland than in vascular tissues in vivo [10].
• In contrast, there was only a slight change in the Bmax values in the spleen and cerebral cortex of KMD-3213-treated rats [11].

Associations of Silodosin with other chemical compounds

• [3H]-PZ binding sites consisted of low- and high-affinity sites for KMD-3213 (pKi = 7.6 and 10.7, respectively), for WB4101 (pK = 8.1 and 10.0) and for YM-617 (pKi = 8.7 and 10.8) [12].

Gene context of Silodosin

• Effect of KMD-3213, an alpha 1a-adrenoceptor-selective antagonist, on the contractions of rabbit prostate and rabbit and rat aorta [9].

Analytical, diagnostic and therapeutic context of Silodosin

• 5. The findings of the present study demonstrated that up-regulation of alpha-1 AR is selectively caused by prazosin treatment in some tissues but neither by KMD-3213 treatment nor by chemical denervation with reserpine [5].
• Selective and sustained occupancy of prostatic alpha1-adrenoceptors by oral administration of KMD-3213 and its plasma concentration in rats [11].
• Furthermore, flow cytometry analysis of alpha1A-AR-selective drug, KMD-3213, and alpha1B-AR-selective drug, CEC, revealed that the major determinant of the subtype selectivity of each drug is different [13].
• 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 [6].

References