Additive effect of oral LDD175 to tamsulosin and finasteride in a benign prostate hyperplasia rat model.

Abstract

ObjectiveWe investigated the benefits of the BKCa agonist 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid (LDD175) combined with tamsulosin and finasteride, in a benign prostatic hyperplasia (BPH) rat model.Materials and methodsCastration was performed by bilateral orchiectomy under ketamine anesthesia. A rat model of BPH was established by daily intramuscular administration of testosterone propionate plus 17β-estradiol for 8 weeks. Model rats were administered combinations of 20 mg/kg LDD175, 0.01 mg/kg tamsulosin and 1 mg/kg finasteride once daily by oral gavage for 4 weeks from week 6 to 9 post-surgery. Intraurethral pressure induced by electrostimulation of the hypogastric nerve was measured at the end of administration. Body and genitourinary organ weights were recorded, serums were assayed for hormone concentrations, and tissues were subjected to histopathology, and analyses of α1-adrenoceptor mRNA and protein expression levels after treatment.ResultsCombined LDD175, tamsulosin, and finasteride significantly decreased prostatic index, serum hormone levels, epithelial thickness, and prostate expression of α1-adrenoceptors in BPH model rats. The 3-drug combination was more effective than any other combination or LDD175 alone.ConclusionThese results suggest that LDD175 addition to tamsulosin and finasteride may be beneficial for the treatment of BPH patients who do not respond to tamsulosin plus finasteride.