Naftopidil DiHCl

Naftopidil diHCl possesses 5-HT1A agonistic properties in addition to being an α1-adrenoceptor antagonist. ^[1] Naftopidil has growth inhibitory effect in androgen-sensitive and -insensitive human prostate cancer cell lines. Naftopidil inhibits the growth of androgen-sensitive LNCaP cells and androgen-insensitive PC-3 cells with IC50 of 22.2 μM and 33.2 μM, respectively. Cell growth inhibition by Naftopidil is due to the arrest of the G1 cell cycle. Expressions of p27^kip1 and p21^cip1 are significantly increased in LNCaP cells treated with Naftopidil. In PC-3 cells, Naftopidil induces p21^cip1 but not p27^kip1. ^[2] Naftopidil produces a concentration-dependent inhibition of collagen-induced Ca²⁺ mobilization, maximum inhibition (22.9%) occurring with 40 μM Naftopidil. The adrenaline-induced rise in [Ca²⁺]_i is inhibited dose dependently by Naftopidil. ^[3] Naftopidil is significantly more effective than tamsulosin in relieving nocturia. ^[4] Naftopidil induces G(1) cell-cycle arrest in both PCa cells and PrSC. In Naftopidil-treated PrSC, total interleukin-6 protein is significantly reduced with increased suppression of cell proliferation. ^[5]

Cell cycle analysis is performed by flow cytometry. Cells are treated with either 20 μM Naftopidil (LNCaP), 40 μM Naftopidil (PC-3) or vehicle (0.1% DMSO) for 24 hours, then trypsinized and washed once with phosphate-buffer saline (PBS), fixed in 70% ethanol and stored at 4 °C for subsequent cell cycle analysis. Fixed cells are washed with PBS and incubated with PBS containing 20 μg/mL RNaseA and 0.3% NP-40 for 30 minutes at 37 °C, then stained with 50 μg/mL propidium iodide (PI) for 30 minutes at 4 癈 in the dark. The DNA content of 1 ?10⁶ stained cells is analyzed on a FACS Caliburflow cytometer. The fractions of cells in the G0/G1, S and G2/M phases are calculated using Cell Quest software.

Oral administration of Naftopidil to nude mice inhibits the growth of PC-3 tumors as compared to vehicle-treated controls. Naftopidil improves bladder capacity and relaxed voiding via inhibition of afferent nerve activity. ^[2] Naftopidil (0.1 μg–30 μg) transiently abolishes isovolumetric rhythmic bladder contraction. The amplitude of bladder contraction is decreased by intrathecal injection of naftopidil (3 μg–30 μg). ^[6] Naftopidil selectively inhibits the phenylephrine-induced increase in prostatic pressure compared with mean blood pressure in the anesthetized dog model. ^[7]