Comparison of two α₁‐adrenoceptor antagonists, naftopidil and tamsulosin hydrochloride, in the treatment of lower urinary tract symptoms with benign prostatic hyperplasia: a randomized crossover study

Abstract

OBJECTIVES To compare the efficacy of two α1‐adrenoceptor antagonists, α1A‐adrenoceptor‐selective tamsulosin hydrochloride and α1D‐adrenoceptor‐selective naftopidil, in the treatment of lower urinary tract symptoms (LUTS) with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS Thirty‐four patients (mean age 72.4 years, sd 4.3, range 66–79) with LUTS (International Prostate Symptom Score, IPSS >8) secondary to BPH were enrolled in a randomized crossover study. Seventeen patients were initially prescribed naftopidil 50 mg for 4 weeks, followed by tamsulosin 0.2 mg for 4 weeks (group A); another 17 were initially prescribed tamsulosin 0.2 mg, followed by naftopidil 50 mg (group B). Patients changed to the alternative treatment after a 1‐week washout period. Efficacy criteria were improvement in LUTS (IPSS), quality of life (QoL), uroflowmetry, and pressure‐flow study (PFS) values based on the treatment with each agent. RESULTS At baseline there were no significant differences between the groups in IPSS, QoL, uroflowmetry values or PFS values, except for the volume at maximum desire to void. After treatment with each agent, the IPSS and QoL were significantly improved and the reduction in bladder outlet obstruction confirmed by PFS. Naftopidil was significantly more effective than tamsulosin in relieving nocturia. The increases from baseline (before treatment) to the endpoint (after treatment with each agent) in the volume at first desire and maximum desire to void were significantly higher with naftopidil than with tamsulosin. Involuntary contractions disappeared in two patients with relief of nocturia with naftopidil, but not with tamsulosin. The decrease in other symptoms of the IPSS, QoL, increase in uroflowmetry values and changes in other PFS values were similar for both agents. CONCLUSIONS The two agents provided similar efficacy in the treatment of LUTS with BPH. However, naftopidil was better than tamsulosin for nocturia. The disappearance of involuntary contraction and the greater increase in first‐desire volume with naftopidil may be associated with the relief of nocturia. The α1D‐adrenoceptor antagonist is effective in alleviating both voiding and storage symptoms. The α1D‐adrenoceptor antagonist may be more effective than the α1A‐adrenoceptor antagonist in LUTS with BPH.

Naftopidil, a selective α‐1 adrenoceptor antagonist, inhibits growth of human prostate cancer cells by G1 cell cycle arrest

“…1 The incidence and mortality of prostate cancer are still lower in Japan than in western countries, but both rates are rapidly increasing recently. Age-adjusted incidence and mortality of prostate cancer have risen from 7.1% in 1975 to 19.9% in 1998, and from 0.5% in 1950 to 8.6% in 2000. 2 In regard to treatment, organ-confined prostate cancer is curable with surgery or radiotherapy, but management of non-organ-confined disease fails in many cases.…”

“…16 Several reports demonstrated that naftopidil improved bladder capacity and relaxed voiding via inhibition of afferent nerve activity, 17,18 and clinically improved not only obstructive voiding symptoms but also storage symptoms associated with BPH. 19,20 Kyprianou and Benning demonstrated that doxazosin and terazosin (quinazoline-derived a-1 adrenoceptor antagonists) had growth-inhibitory effects in human prostate cancer cell lines. 21 Doxazosin induced apoptosis in prostate cancer cells, although that action was independent of the capacity to antagonize a-1 adrenoceptors.…”

Crystal structure of 2-[[4-[2-[4-(4-methoxyphenyl)-1-piperazinyl]ethyl]phenyl] methyl]-1H-isoindole-1,3(2H)-dione, C28H29N3O3

“…Naftopidil is a derivative of arylpiperazine ether and a specific antagonist targeted for the adrenergic receptor [5], which has already been regarded as one of the most commonly utilized antagonists targeted for the adrenergic receptor to treat the benign prostatic hyperplasia (BPH) in Japan [6]. The arylpiperazine derivative mentioned in this paper is a subselective antagonist for BPH [7].…”

Management of benign prostatic hyperplasia with silodosin

“…In a cross-over study comparing tamsulosin (α 1A -AR  α 1D -AR) with naftopidil (α 1D -AR  α 1A -AR), relief of storage symptoms was significantly better in subjects given naftopidil. 1,[51][52][53][54] However, this issue is still controversial and different results have been reported by other authors. 1,55,56 Recently, Kira and colleagues 57 studied the efficacy of silodosin in 85 patients with LUTS/BPH who were resistant to tamsulosin (n = 39) or naftopidil (n = 46), and reported a rapid and significant decrease in scores of decreased urinary stream and nocturia (both p  0.01), which were the most bothersome symptoms among IPSS.…”