alpha1-adrenoceptor antagonists are first-line agents for the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia, while their adverse effects on sexual function are reported frequently in recent years, especially the induction of ejaculatory dysfunction. This review presents the distribution of alpha 1-adrenoceptors in the male genital system and the relationship of alpha1-adrenoceptors with ejaculatory function. It also highlights the interesting phenomenon of ejaculatory dysfunction related to these drugs and its possible mechanism, with the intention to provide some essential clues for further research on this problem as well as some references to safer use of these drugs in clinical settings.
Adrenergic alpha-1 Receptor Antagonists ; Adrenergic alpha-Antagonists ; adverse effects ; pharmacology ; Ejaculation ; physiology ; Erectile Dysfunction ; chemically induced ; physiopathology ; Humans ; Male ; Receptors, Adrenergic, alpha-1 ; physiology

Benign prostatic hyperplasia (BPH) is a common senile disease, and its main clinical manifestation is lower urinary tract symptom (LUTS), which has long been afflicting old male patients. Previous study showed that alpha1-receptor in the prostate was involved in the development of LUTS. At present, alpha1-receptor blocker is generally accepted as a choice drug for treating BPH and relieving LUTS. The article reviews the tissue distribution of alpha1-receptor and clinical application of alpha1-receptor blocker.
Adrenergic alpha-1 Receptor Antagonists ; Adrenergic alpha-Antagonists ; adverse effects ; pharmacokinetics ; therapeutic use ; Humans ; Male ; Prostatic Hyperplasia ; drug therapy ; Receptors, Adrenergic, alpha-1 ; analysis

OBJECTIVETo study the biological activities of several alpha1-adrenoceptor antagonists in vitro.

METHODSThe anococcygeal muscle from male Sprague-Dawley rats (300-350 g) was isolated, removed and suspended in a 20-ml organ chamber containing Krebs solution at 37 degrees C, pH 7.4. The muscle preparations were set at a resting tension of 1.0 g and allowed to equilibrate for 1 h in the Krebs solution. After thorough washing, the anococcygeal muscle preparations were examined for the effects of the tested compounds with increased concentrations on its contractile/relaxant responses and the pA2 of antagonistic activity was assessed.

RESULTSSome of the target compounds displayed blocking activity to alpha1-adrenoceptor.

CONCLUSIONCompounds WB IV-1 and WB IV-3 showed good inhibiting activity, and were worth further studying.

Adrenergic alpha-1 Receptor Antagonists ; Adrenergic alpha-Antagonists ; pharmacology ; Anal Canal ; drug effects ; Animals ; In Vitro Techniques ; Male ; Muscle Contraction ; drug effects ; Rats ; Rats, Sprague-Dawley

AIMTo establish new methods for the chiral separation and preparation of three new drugs, alfuzosin, terazosin and doxazosin.

METHODSBy optimizing factors which affect the chiral separation, modifier of solvent, chiral additive, pH of mobile phase, modifier of organic base and stationary phase, the optimum condition for chiral separation were selected. The preparation of enantiomers was carried out on semi-preparative reverse phase column (7.8 mm x 250 mm C4 5 microns). Acetonitrile-water modified by the addition of carboxymethyl-beta-cyclodextrin (2%-5%, w/v) was applied as chiral mobile phase.

RESULTSThe enantiomers of three new drugs were base-line-separated and milligram-scale samples of enantiomer were obtained.

CONCLUSIONThe newly established method can be used in research and development of the enantiomers of three new drugs.

Adrenergic alpha-1 Receptor Antagonists ; Adrenergic alpha-Antagonists ; isolation & purification ; Chromatography, High Pressure Liquid ; methods ; Doxazosin ; isolation & purification ; Molecular Structure ; Prazosin ; analogs & derivatives ; isolation & purification ; Quinazolines ; isolation & purification

OBJECTIVESTo evaluate the efficacy of selective alpha 1A-adrenergic receptor antagonists for the treatment chronic abacterial prostatitis/chronic pelvic pain syndrome (CPPS).

METHODSFrom October 2000 to September 2001, a selective alpha 1A-adrenergic receptor antagonists, tamsulosin, had been used in 43 patients with CPPS for four weeks. 0.2 mg dosage was given daily, and uroflowmetry was followed. Symptom scores were evaluated by the NIH-chronic prostatitis symptom index (NIH-CPSI) before and after the treatment.

RESULTSThese patients had a clinically significant response to the treatment of tamsulosin. Of these, thirty two patients (74.5%) responded to one month therapy and had a decrease in NIH-CPSI scores, while maximal urinary flow rate (MFR) and average urinary flow rate (AFR) in patients with poor MFR improved 30.4% and 65.4%, respectively. No severe side effects were observed.

CONCLUSIONSIt is suggested that Tamsulosin, a selective alpha 1A-adrenergic receptor antagonist, is effective in the treatment of CPPS.

Adolescent ; Adrenergic alpha-1 Receptor Antagonists ; Adrenergic alpha-Antagonists ; therapeutic use ; Adult ; Chronic Disease ; Humans ; Male ; Middle Aged ; Pelvic Pain ; drug therapy ; etiology ; Prostatitis ; complications ; drug therapy ; Receptors, Adrenergic, alpha-1 ; Sulfonamides ; therapeutic use ; Treatment Outcome

Dual dopamine D2/5-HT2A receptor antagonists have potent activity and are referred to atypical antipsychotics due to their lower propensity to elicit EPS and their moderate efficacy toward negative symptoms. However, an on-going challenge in developing atypical antipsychotics drugs is to maintain the favorable profiles and avoid of cardiovascular risk. In this paper, comparative pharmacophore analysis of dual dopamine D2/5-HT2A receptor antagonists, hERG K+ channel blockers, and alA adrenoceptor antagonists is carried out, and the results could give some insight into multi-target drug design.
Adrenergic alpha-1 Receptor Antagonists ; Dopamine D2 Receptor Antagonists ; Drug Delivery Systems ; Drug Design ; ERG1 Potassium Channel ; Ether-A-Go-Go Potassium Channels ; antagonists & inhibitors ; chemistry ; Molecular Conformation ; Molecular Structure ; Receptor, Serotonin, 5-HT2A ; chemistry ; Receptors, Adrenergic, alpha-1 ; chemistry ; Receptors, Dopamine D2 ; chemistry ; Serotonin 5-HT2 Receptor Antagonists ; Structure-Activity Relationship

The epidemiological survey shows that primary hypertension is one of the independent risk factors in the development and the progress of BPH, 25 percent of old male patients aged 60 or more suffer from the two diseases at the same time, which grievously affects their quality of life. There is little literature about the appropriate therapeutic regimen of BPH associated hypertension. The article reviews the progress in the studies of alpha1-adrenoceptor blocker for BPH associated hypertension, and explores the main problems facing us and ventures the prospects for the development in this field.
Adrenergic alpha-1 Receptor Antagonists ; Adrenergic alpha-Antagonists ; adverse effects ; therapeutic use ; Aged ; Aged, 80 and over ; Humans ; Hypertension ; complications ; drug therapy ; Male ; Middle Aged ; Prazosin ; adverse effects ; analogs & derivatives ; therapeutic use ; Prostatic Hyperplasia ; complications ; drug therapy

PURPOSE: Tamsulosin 0.2 mg is used widely in Asian people, but the low dose has been studied less than tamsulosin 0.4 mg or other alpha blockers of standard dose. This study investigated the efficacy and safety of tamsulosin 0.2 mg by a meta-analysis and meta-regression. MATERIALS AND METHODS: We conducted a meta-analysis of efficacy of tamsulosin 0.2 mg using International Prostate Symptom Score (IPSS), maximal urinary flow rate (Qmax), post-voided residual volume (PVR), and quality of life (QoL). Safety was analyzed using adverse events. Relevant studies were searched using MEDLINE, EMBASE, and Cochrane library from January 1980 to June 2013. RESULTS: Ten studies were included with a total sample size of 1418 subjects [722 tamsulosin 0.2 mg group and 696 other alpha-blockers (terazosin, doxazosin, naftopidil, silodosin) group]. Study duration ranged from 4 to 24 weeks. The pooled overall standardized mean differences (SMD) in the mean change of IPSS from baseline for the tamsulosin group versus the control group was 0.02 [95% confidence interval (CI); -0.20, 0.25]. The pooled overall SMD in the mean change of QoL from baseline for the tamsulosin group versus the control group was 0.16 (95% CI; -0.16, 0.48). The regression analysis with the continuous variables (number of patients, study duration) revealed no significance in all outcomes as IPSS, QoL, and Qmax. CONCLUSION: This study clarifies that tamsulosin 0.2 mg has similar efficacy and fewer adverse events compared with other alpha-blockers as an initial treatment strategy for men with lower urinary tract symptoms.
Adrenergic alpha-1 Receptor Antagonists/*administration & dosage/therapeutic use ; Adrenergic alpha-Antagonists ; Dose-Response Relationship, Drug ; Humans ; Male ; Middle Aged ; Prostatic Hyperplasia/*complications ; *Quality of Life ; Sulfonamides/*administration & dosage/therapeutic use

OBJECTIVETo investigate the effect and mechanism of alpha1-adrenoceptor blocker combined with antibiotics in the treatment of chronic prostatitis.

METHODSEighty patients with chronic prostatitis were divided into two groups, one treated with alpha1-adrenoceptor blocker (Terazosin 2 mg qn) and Levo-ofloxacin (0.2 bid), and the other given Levo-ofloxacin (0.2 bid) alone for 6 weeks. Chronic prostatitis symptom index (CPSI), urodynamic data and prostatic secretion examination were compared before and after treatment.

RESULTSThe CPSI score of the treated group decreased from 31.8 +/- 7.4 to 15.5 +/-6.6, while that of the control group decreased from 30.9 +/- 7.1 to 21.4 +/- 6.2. There was significant difference between the two groups (P < 0.05). The maximum flow rates before and after the combined treatment were 16.5 +/- 6.3 ml/s and 20.4 +/- 4.6 ml/s, while those before and after Levo-ofloxacin administration were 16.1 +/-5.8 ml/s and 17.3 +/- 6.8 ml/s. The difference was significant (P < 0.05). The maximum urethral pressure of the combined treatment group decreased from 92.5 +/- 15.3 cm H2O to 72.5 +/- 13.4 cm H2O, while that of the control group decreased from 93.2 +/- 14.8 cm H2O to 91.7 +/- 13.6 cm H2O.

CONCLUSIONAlpha1-adrenoceptor blocker can lower the intraurethral pressure, which prevents urine from refluxing to the prostate. Alpha1-adrenoceptor blocker combined with antibiotics is effective for chronic prostatitis.

Adrenergic alpha-1 Receptor Antagonists ; Adrenergic alpha-Antagonists ; administration & dosage ; Adult ; Anti-Bacterial Agents ; administration & dosage ; Chronic Disease ; Drug Therapy, Combination ; Humans ; Male ; Middle Aged ; Prostatitis ; drug therapy ; physiopathology ; Urodynamics

OBJECTIVESTo evaluate the clinical efficacy and safety of Naftopidil tablet in treating benign prostatic hyperplasia.

METHODSEighty BPH patients were divided into two groups randomly by double-blind, double-simulated and active control parallel study trials. Forty patients in treatment group were given Naftopidil tablet 25 mg, p.o., qn for 42 days, while 40 patients in control group were given Tamsulosin 0.2 mg, p.o., qn for 42 days. Statistical analysis was given from 77 cases in the groups. Estimation of the efficacy was done by the change of major indexes include international prostate symptom score (IPSS), maximum flowrate (Qmax) and secondary indexes such as quality of life (QOL), residual urine (Ru) and volume of prostate (V).

RESULTSThe changes of IPSS, Qmax, QOL had significant difference between two groups before and after treatment(P < 0.05). The change of Ru had no significant difference between two groups before and after treatment (P > 0.05) while there was significant difference between two groups after six-week treatment(P < 0.05). The change of V had no significant difference (P > 0.05). The adverse reactions in both groups were mild, and there was no significant difference between two groups(P > 0.05).

CONCLUSIONSNaftopidil tablet was safe and effective in treating benign prostatic hyperplasia.

Adrenergic alpha-1 Receptor Antagonists ; Adrenergic alpha-Antagonists ; therapeutic use ; Aged ; Double-Blind Method ; Humans ; Male ; Middle Aged ; Naphthalenes ; adverse effects ; therapeutic use ; Piperazines ; adverse effects ; therapeutic use ; Prostatic Hyperplasia ; drug therapy ; psychology ; Quality of Life ; Tablets