Comparison of the antagonistic activity of tamsulosin and doxazosin at vascular α1-adrenoceptors in humans

₁-Adrenoceptor blockers such as prazosin and doxazosin are used to treat hypertension as well as benign prostatic hyperplasia (BPH), whereas the new _l-adrenoceptor blocker tamsulosin is used only for BPH and does not reduce blood pressure at the doses used to relax prostatic smooth muscle. In contrast to prazosin, tamsulosin has a higher affinity for prostatic than vascular ₁-adrenoceptors in vitro. The functional correlate of this observation in humans is the subject of this study. The ₁-adrenoceptor blockade by oral tamsulosin (0.2 mg), doxazosin (1 mg) or placebo on finger tip vascular and dorsal hand venous ₁-adrenoceptors stimulated by cold treatment (immersion in ice water) and the _l-adrenoceptor agonist phenylephrine, was thus studied in a 3-way crossover study in eight, healthy, male adults. Finger tip vasoconstriction after cold stimulation was assessed by laser Doppler flowmetry. A linear variable differential transformer was used to assess the drug effect on phenylephrine-induced venoconstriction. All study parameters were assessed at around 2 and 3.5 h after oral intake of doxazosin and tamsulosin respectively. The drug plasma levels were not significantly different. No significant differences were found for blood pressure or heart rate in the three treatments in supine and erect position. The reduction in finger tip blood flow after cold stimulation was significantly smaller after doxazosin treatment (P<0.01) than after tamsulosin or placebo, whereas there was no significant difference between tamsulosin and placebo treatments. The infusion rate of phenylephrine producing a half-maximum venoconstriction was significantly larger after doxazosin than after tamsulosin (P<0.05) or placebo (P<0.01), whereas there was again no significant difference between tamsulosin and placebo treatments. The data suggest that, at doses producing equal plasma levels after single oral doses in human subjects, the blocking activity at vascular ₁-adrenoceptors is lower for tamsulosin than for doxazosin.     

Apoptotic activity of doxazosin on prostate stroma in vitro is mediated through an autocrine expression of TGF-beta1

BACKGROUND: Doxazosin, an alpha-adrenergic antagonist, has been shown to induce apoptosis in prostatic stromal cells. The mechanism of this apoptotic action by Doxazosin remains undefined. The present study was carried out to demonstrate that the effect of Doxazosin on apoptosis of prostate stromal cells is mediated through an autocrine action of TGF-beta1. METHODS: Primary cultures of human prostate cells were treated with varying concentrations of Doxazosin (0, 0.1, 1, 10, and 100 microM) for a period up to 3 days. At the end of the 3-day culture, cell numbers were counted. Apoptosis was assessed by a colorimetric terminal deoxyribonucleotide transferase labeling technique. TGF-beta1 was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared to control cultures, cell numbers were significantly decreased as much as 68.4% in cultures treated with 10 microM of Doxazosin after 3 days incubation, while apoptosis increased by 64.7% in cultures treated with the same concentration of Doxazosin after 24 h. This decrease in cell number was reversed when antibody to TGF-beta1 was added to these cultures. Addition of TGF-beta1 (0, 1.0, and 10 ng/mL) to the cultures also decreased the cell numbers. Quantitation of TGF-beta1 in lysates of cells by ELISA revealed that the cells treated with Doxazosin (10 microM) produced as much as 62.5% more TGF-beta1 than in that of untreated cells. CONCLUSIONS: These results demonstrate that the apoptotic effect of Doxazosin on human prostatic stromal cells is mediated through an autocrine production of TGF-beta1.     

多沙唑嗪联合帕罗西汀治疗非细菌性慢性前列腺炎的疗效

目的观察多沙唑嗪联合帕罗西汀治疗非细菌性慢性前列腺炎的疗效。方法选择2017年6月至2018年6月深圳市龙华区中心医院门诊治疗的非细菌性慢性前列腺炎患者120例为研究对象,采用随机数字表法分为对照组和观察组,每组60例。对照组给予单一多沙唑嗪治疗,观察组给予多沙唑嗪联合帕罗西汀治疗,连续治疗4个疗程(7 d为1个疗程)。比较两组的疗效和不良反应,观察两组治疗前后血清白细胞介素-2(IL-2)、C-反应蛋白(CRP)、肿瘤坏死因子γ(TNF-γ)水平的变化,评估两组治疗后机体炎症及焦虑、抑郁等负性情绪改善情况。结果观察组治疗总有效率(96. 67%)高于对照组(86. 67%),差异有统计学意义(P <0. 05);观察组不良反应发生率(8. 33%)高于对照组(6. 67%),但差异无统计学意义(P> 0. 05)。与治疗前比较,治疗后两组患者慢性前列腺炎症状(NIH-CPSI)评分、焦虑自评量表(SAS)及抑郁自评量表(SDS)评分均降低,IL-2、CRP以及TNF-γ等细胞因子水平均降低,且观察组上述指标降幅均高于对照组,差异均有统计学意义(P <0. 05)。结论多沙唑嗪联合帕罗西汀治疗非细菌性慢性前列腺炎疗效确切,可缓解患者负性情绪和机体炎性症状,值得推广应用。     

西地那非联合多沙唑嗪治疗早泄的临床观察

目的 探讨枸橼酸两地那非联合多沙唑嗪控释片治疗早泄的临床效果.方法 记录30例患者治疗前后阴道内射精潜伏期,同时记录夫妻性生活的满意程度.结果 治疗前,阴道内射精潜伏期为(0.80±0.20)min,治疗后为(3.60±0.56)min,差异有显著性(P<0.01).治疗后夫妻性生活满意度显著提高.结论 枸橼酸西地那非联合多沙唑嗪片可延长阴道内射精潜伏期,治疗早泄有良好疗效.     

前列舒通胶囊联合多沙唑嗪治疗良性前列腺增生临床观察

目的初步探讨中成药前列舒通胶囊联合多沙唑嗪治疗良性前列腺增生的临床疗效。方法40例BPH患者,随机分为两组,联合治疗组给予前列舒通胶囊,3次／d,3粒／次,多沙唑嗪4mg 1次/d,对照组单独服用多沙唑嗪治疗。用药3月,评估治疗前后国际前列腺症状评分（IPSS）、前列腺体积、最大尿流率（Qmax）、残余尿量,并记录不良事件。结果治疗3月后,两组间比较,联合用药组IPSS评分、前列腺体积变化较对照组明显,组间差异有统计学意义（P〈0．01）,治疗3月后两组间Qmax、残余尿量差异无统计学意义（P〉0．05）。结论前列舒通胶囊与α-受体阻滞剂联合用药能改善BPH症状,缩小前列腺体积,提高最大尿流率;联合用药优于单独使用α-受体阻滞剂。     

甲磺酸多沙唑嗪缓释剂治疗膀胱出口梗阻术后膀胱痉挛的临床观察

目的 探讨甲磺酸多沙唑嗪缓释剂(可多华)对膀胱痉挛的防治作用,总结膀胱痉挛的治疗措施方法 256例患者分为两组.实验组:可多华4 mg临睡前服用,维生素K3 8 mg 3次/d;对照组:溴丙胺太林15 mg 2次/d,维生素K3 8 mg 3次/d.结果 实验组和对照组在治疗后的膀胱痉挛发生率不同,经卡方检验,差异有统计学意义(P<0.01).结论 可多华可降低膀胱三角区及后尿道的平滑肌张力,从而解除膀胱痉挛.     

Insights into cardio-oncology: Polypharmacology of quinazoline-based α1-adrenoceptor antagonists

New uses of cardiovascular drugs with proven experience are emerging, including for treating cancer. Quinazoline is a compound made up of two fused six member simple aromatic rings, benzene and pyrimidine rings, with several biological effects. Cardiologists first used quinazoline-based α₁-adrenoceptor antagonists prazosin, doxazosin, and terazosin; currently available data support their use as safe, well tolerated, and effective add-on therapy in uncontrolled hypertension with additional favourable metabolic effects. Recent findings highlight the anticancer effects of quinazoline-based α₁-adrenoceptor antagonists, indicating that they may have a significant role in uncontrolled hypertensive cancer patients without signs of ischemia.     

Commentary: Doxasozin for Alcoholism

Recent preclinical and clinical evidence using prazosin indicates that α₁‐blockade may represent a new approach to treat alcohol dependence (AD). While most of the alcohol research on α₁‐blockade has been conducted testing prazosin, O'Neil and colleagues recently performed a set of preclinical experiments testing another α₁‐blocker, doxazosin, which has a longer half‐life that may enhance clinical utility. Doxazosin and prazosin share the same chemical structure, in which the central element is a piperazine ring. O'Neil and colleagues' main results are that doxazosin significantly reduced alcohol intake without affecting locomotor activity. As such, O'Neil and colleagues provide the first preclinical evidence of the possible role of doxazosin in AD. Additional translational research is needed to further test this hypothesis.     

索利那新联合多沙唑嗪治疗前列腺增生症的临床观察

目的评估索利那新联合多沙唑嗪治疗前列腺增生症合并膀胱过度活动症的疗效。方法入组84例前列腺增生症合并膀胱过度活动症患者,分为治疗组,采用索利那新5mg,多沙唑嗪4mg,每日一次口服。对照组采用多沙唑嗪4mg,每日一次口服。为期4周。结果两组间基线资料比较差异无统计学差异。用药4周后,联合用药组及多沙唑嗪组IPSS评分及刺激症状评分均改善(P<0.05)。治疗后两组间比较显示:联合用药组IPSS评分的改善优于多沙唑嗪组(P<0.05),联合用药组刺激评分的改善优于多沙唑嗪组(P<0.05),治疗4周后两组间Qmax、残余尿差异无统计学意义(P>0.05)。结论索利那新联合多沙唑嗪治疗前列腺增生症合并膀胱过度活动症较单用多沙唑嗪更有效。