The safety of perampanel in different disorders and doses: A meta-analysis.

PURPOSE: To investigate the safety of perampanel in different disorders and doses. METHODS: Embase, the Cochrane Library, Medline, and ClinicalTrials.gov were searched from inception to July 2022 for randomized controlled trials (RCTs). The meta-analysis was performed by using Review Manager 5.3 and R 4.2.1 software. RESULTS: A total of 17 RCTs with 5711 subjects were included in the final analysis. The double-blind treatment phase was from 12 weeks to 48 weeks. Our results showed that 11 adverse events (aggression, ataxia, balance disorder, dizziness, fall, fatigue, irritability, rash, somnolence, vertigo, and weight increase) were statistically significantly associated with perampanel, and 4 of them (ataxia, dizziness, fatigue, and somnolence) showed a clear dose-response relationship. Psychiatric adverse events occurred most frequently among serious treatment-emergent adverse events (TEAEs). At 8 mg/day, seven adverse events (aggression, balance disorder, dizziness, fatigue, irritability, vertigo, and weight increase) occurred more frequently in patients with epilepsy than in patients with other disorders, whereas dose discontinuation rates due to adverse events were lower in patients with epilepsy than in patients with other disorders. CONCLUSION: The safety profile of perampanel is dependent on diseases and dose. The risk of adverse events was statistically significantly higher, with doses exceeding 4 mg/day. Despite a higher risk of adverse events, patients with epilepsy had a lower perampanel discontinuation rate than patients with other disorders.

Different dosage regimens of nifedipine, labetalol, and hydralazine for the treatment of severe hypertension during pregnancy: a network meta-analysis of randomized controlled trials.

OBJECTIVES: This network meta-analysis aimed to compare the efficacy and safety of intravenous (IV) hydralazine, oral nifedipine, and IV labetalol with different dosage regimens in the treatment of severe hypertension during pregnancy. METHODS: A comprehensive literature search was performed on PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) exploring the effects of hydralazine, nifedipine, and labetalol in the treatment of severe hypertension during pregnancy. RESULTS: A total of 21 RCTs with 2183 patients comparing 7 regimens (oral nifedipine 50,60,90 mg; hydralazine 15,25 mg; and labetalol 220,300 mg) were identified. Compared with IV labetalol 300 mg, nifedipine 50,60, and 90 mg significantly improved the successful treatment rate of severe hypertension during pregnancy, nifedipine 50 and 90 mg and IV hydralazine 25 mg required significantly fewer doses to achieve target blood pressure (BP), and nifedipine 50 mg took significantly shorter time to achieve target BP. Subgroup analysis showed that only nifedipine 50 mg tablets, not capsules, required a significantly shorter time and fewer doses to achieve target BP than IV labetalol 300 mg. Moreover, nifedipine 60,90 mg showed superior effectiveness than IV hydralazine 15,25 mg in the successful treatment rate of severe hypertension during pregnancy. SUCRA analysis suggested that nifedipine 50,60,90 mg as the better regimens with the lower rates of overall ADR and neonatal complications. CONCLUSION: These findings demonstrated the superiority of oral nifedipine 50,60,90 mg, especially oral nifedipine 50 mg tablets, in the treatment of severe hypertension during pregnancy than IV labetalol 300 mg, while oral nifedipine 60,90 mg also showed superiority in the successful treatment rate of severe hypertension during pregnancy than IV hydralazine 15,25 mg. However, the limitations of the underlying data indicate that future large-scale and rigorous RCTs are needed to confirm such findings.

ROCK inhibitor fasudil reduces the expression of inflammatory factors in LPS-induced rat pulmonary microvascular endothelial cells via ROS/NF-κB pathway.

BACKGROUND: Inflammation plays a major role in the pulmonary artery hypertension (PAH) and the acute lung injury (ALI) diseases. The common feature of these complications is the dysfunction of pulmonary microvascular endothelial cells (PMVECs). Fasudil, the only Rho kinase (ROCK) inhibitor used in clinic, has been proved to be the most promising new drug for the treatment of PAH, with some anti-inflammatory activity. Therefore, in the present study, the effect of fasudil on lipopolysaccharide (LPS)-induced inflammatory injury in rat PMVECs was investigated. METHODS: LPS was used to make inflammatory injury model of rat PMVECs. Thereafter, the mRNA and protein expression of pro-inflammatory factors was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) assay respectively. Intracellular reactive oxygen species (ROS) levels were measured by the confocal laser scanning system. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the content of malondialdehyde (MDA) were determined by using commercial kits according to the manufacturer's instructions. Western blot assay was used to detect the protein expression of nuclear factor kappa B (NF-κB) p65. RESULTS: Fasudil effectively prevented inflammatory injury induced by LPS, which is manifested by the decrease of pro-inflammatory cytokines interleukin-6 (IL-6) and monocyte chenotactic protein-1 (MCP-1). Meanwhile, fasudil dramatically reduced the levels of ROS and MDA, and also elevated the activities of SOD and GSH-Px. Furthermore, the nuclear translocation of NF-κB p65 induced by LPS was also suppressed by fasudil. Additionally, the ROS scavengers N-Acetylcysteine (N-Ace) was also found to inhibit the nuclear translocation of NF-κB and the mRNA expression of IL-6 and MCP-1 induced by LPS, which suggested that ROS was essential for the nuclear translocation of NF-κB. CONCLUSIONS: The present study revealed that fasudil reduced the expression of inflammatory factors, alleviated the inflammatory and oxidative damage induced by LPS in rat PMVECs via ROS-NF-κB signaling pathway.

A network meta-analysis on the efficacy of HER2-targeted agents in combination with taxane-containing regimens for treatment of HER2-positive metastatic breast cancer.

PURPOSE: We performed a network meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of HER2-targeted agents in combination with taxanes and to identify the best strategy for HER2+ metastatic breast cancer (MBC). METHODS: Pubmed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials that evaluated any taxanes+HER2-targeted agents in the treatment of HER2+ MBC. The primary outcome was overall survival (OS). The secondary outcomes included overall response rate (ORR) and progression-free survival (PFS). RESULTS: A total of 13 RCTs were eligible, involving 4941 patients and 10 regimens. The result showed that single-HER2-targeted agent+a taxane did improve the effect on ORR and PFS than taxane alone, but only trastuzumab+a taxane had a significant improvement in OS outcomes. Single-HER2-targeted agent (trastuzumab) combined with taxane-based doublets (taxane+carboplatin/capecitabine/doxorubicin/bevacizumab) showed no further benefit than trastuzumab+a taxane. Doublet-HER2-targeted agents combined with a taxane(trastuzumab+pertuzumab+a taxane) showed further improvement in ORR, PFS, and all OS outcomes than single-HER2-targeted agent+a taxane. Ranking analysis based on their P-scores suggested that trastuzumab+pertuzumab+a taxane was the best combination treatment for all the efficacy outcomes. CONCLUSIONS: These findings demonstrate that combining two HER2-targeted agents (trastuzumab+pertuzumab) with a taxane is much more beneficial for the treatment of HER2+ MBC. Dual HER2-targeted agents combined with a taxane appears to be the preferred application of HER2+ MBC.

Comparative Effectiveness of Taxane-Containing Regimens for Treatment of HER2-Negative Metastatic Breast Cancer: A Network Meta-analysis.

STUDY OBJECTIVES: To compare the effectiveness of different taxane-containing regimens and to identify the best strategy for the treatment of human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). DESIGN: Network meta-analysis of 20 randomized controlled trials (RCTs). PATIENTS: A total of 6577 patients with HER2-negative MBC who received treatment (20 different regimens) with taxanes (paclitaxel [4267 patients] or docetaxel [2310 patients]). MEASUREMENTS AND MAIN RESULTS: The PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched (through March 2019) for RCTs that evaluated any taxane-containing regimens for the treatment of HER2-negative MBC. A network meta-analysis in a Bayesian framework was performed using the random-effects model. We compared the surface under the cumulative ranking (SUCRA) curve for each regimen. Overall, paclitaxel-based combinations were superior to paclitaxel alone in objective response rate (ORR) (odds ratio 1.60, 95% credible interval [CrI] 1.15-2.16) and overall survival (OS) (hazard ratio 1.08, 95% CrI 1.01-1.15). Docetaxel-based combinations were also superior to paclitaxel alone in ORR. Among the paclitaxel-based regimens, based on the results of SUCRA, paclitaxel + bevacizumab + capecitabine was likely to be the most efficacious in improving ORR, OS, and progression-free survival (PFS), whereas paclitaxel + gemcitabine was likely to be the most efficacious in 1-year OS rate. Among the docetaxel-based regimens, based on the results of SUCRA, docetaxel + gemcitabine was likely to be the most efficacious in improving PFS and OS. CONCLUSION: These findings demonstrated that paclitaxel-based combinations can provide significant improvement in ORR and OS compared with paclitaxel alone. The regimens of paclitaxel + bevacizumab + capecitabine, docetaxel + gemcitabine, and paclitaxel + gemcitabine may be superior to other regimens for the treatment of HER2-negative MBC.

Protective effect of berberine on aconite­induced myocardial injury and the associated mechanisms.

Aconitum plants, which have analgesic, diuretic and anti­inflammatory effects, have been widely used to treat various types of disease. However, the apparent toxicity of Aconitum­derived agents, particularly in the cardiovascular system, has largely limited their clinical use. Thus, the present study investigated whether berberine (Ber), an isoquinoline alkaloid, may reduce myocardial injury induced by aconitine (AC) in rats and the underlying mechanisms. Rats (n=40) were randomly divided into four groups: Control, Chuan­wu and Chuan­wu + Ber (8 and 16 mg/kg doses). Electrocardiograms (ECG) of the rats were recorded and serum biomarkers of cardiac function [lactate dehydrogenase (LDH), creatine kinase (CK) and CK­MB] were assayed. Histopathological changes were assessed using myocardial tissue sectioning and hematoxylin and eosin staining. Additionally, the effects of Ber on AC­induced arrhythmias in rats were observed. The changes in ECG following AC perfusion were observed, and the types and onset time of arrhythmias were analyzed. Furthermore, the effects of Ber and AC on papillary muscle action potentials were observed. The results suggested that Ber ameliorated myocardial injury induced by Chuan­wu, which was indicated by reduced arrhythmias and decreased LDH, CK and CK­MB levels in serum. Furthermore, histological damage, including dilation of small veins and congestion, was also markedly attenuated by Ber. In addition, the occurrence of arrhythmias was significantly delayed, and the dosage of AC required to induce arrhythmias was also increased by Ber pretreatment. Additionally, AC­induced changes in action potential amplitude, duration of 30% repolarization and duration of 90% repolarization in the papillary muscle were attenuated by Ber. All of these results indicate that Ber had a preventive effect on acute myocardial injury induced by Chuan­wu and arrhythmias caused by AC, which may be associated with the inhibition of delayed depolarization and triggered activity caused by AC. Thus, combination treatment of Ber with Aconitum plants may be a novel strategy to prevent AC­induced myocardial injury in clinical practice.

Protective effect of berberine on doxorubicin­induced acute hepatorenal toxicity in rats.

Doxorubicin (DOX), a potent broad­spectrum chemotherapeutic agent used for the treatment of several types of cancer, is largely limited due to its serious side effects on non­target organs. Thus, the present study aimed to investigate whether berberine (Ber), an isoquinoline alkaloid, could reduce DOX­induced acute hepatorenal toxicity in rats. Fifty rats were randomly divided into five groups: i) Control group, ii) DOX group, iii) DOX+Ber (5 mg kg) group; iv) DOX+Ber (10 mg kg), and v) DOX+Ber (20 mg kg) group. In the tests, body weight, organ index, general condition and mortality were observed. In addition, the serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total cholesterol (TCHO) and blood urea nitrogen (BUN) were determined to evaluate hepatorenal function. Hepatorenal toxicity was further assessed using hematoxylin and eosin stained sections. Furthermore, the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and malondialdehyde (MDA) in rat serum or tissue homogenate were also assessed to determine the mechanisms of action. Results suggested that pretreatment with Ber ameliorated the DOX­induced liver and kidney injury by lowering the serum ALT, AST, TCHO and BUN levels, and the damage observed histologically, such as hemorrhage and focal necrosis of liver and kidney tissues induced by DOX were also attenuated by Ber. Furthermore, Ber also exerted certain antioxidative properties through reversing the changes in the levels of MDA, SOD, GSH and MDA induced by DOX. These findings indicate that Ber has protective effects against DOX­induced acute hepatorenal toxicity in rats. Combination of Ber with DOX is a novel strategy that has the potential for protecting against DOX­induced hepatorenal toxicity in clinical practice.

Efficacy and Safety of Pulmonary Arterial Hypertension-specific Therapy in Pulmonary Arterial Hypertension: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Previous meta-analyses of pulmonary arterial hypertension (PAH)-specific therapy for PAH pooled PAH-specific combination therapy and monotherapy. This flaw may threaten the authenticity of their findings. METHODS: PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials that evaluated any PAH-specific medications in the treatment of PAH. We calculated ORs with 95% CIs for dichotomous data and standardized mean differences for continuous data. RESULTS: In total, 35 randomized controlled trials involving 6,702 patients were included. In monotherapy vs placebo/conventional therapy, significance was obtained in mortality reduction (OR, 0.50 [95% CI, 0.33 to 0.76]; P = .001), 6-min walk test (mean difference, 31.10 m [95% CI, 25.40 to 36.80]; P < .00001), New York Heart Association/World Health Organization functional class (OR, 2.48 [95% CI, 1.51 to 4.07]; P = .0003), and hemodynamic status based on mean pulmonary artery pressure, pulmonary vascular resistance, cardiac index, and incidence of withdrawal due to adverse effects. In combination therapy vs monotherapy, significance was reached for the 6-min walk test (mean difference, 19.96 m [95% CI, 15.35 to 24.57]; P < .00001), functional class (OR, 1.65 [95% CI, 1.20 to 2.28]; P = .002), hemodynamic status, and incidence of withdrawal due to adverse effects (OR, 2.01 [95% CI, 1.54 to 2.61]; P < .00001) but not for mortality reduction (OR, 0.98 [95% CI, 0.57 to 1.68]; P = .94). CONCLUSIONS: Our meta-analysis revealed that PAH-specific monotherapy could improve mortality, exercise capacity, functional class, and hemodynamic status compared with placebo or conventional therapy. However, combination therapy could further improve exercise capacity, functional class, and hemodynamic status compared with monotherapy, but it had no proven effect on mortality. Combination therapy had a much higher incidence of withdrawal due to adverse effects than monotherapy.

Exogenous melatonin for sleep disorders in neurodegenerative diseases: a meta-analysis of randomized clinical trials.

The purpose of this work is to investigate the efficacy of exogenous melatonin in the treatment of sleep disorders in patients with neurodegenerative disease. We searched Pubmed, the Cochrane Library, and ClinicalTrials.gov, from inception to July 2015. We included randomized clinical trials (RCTs) that compared melatonin with placebo and that had the primary aim of improving sleep in people with neurodegenerative diseases, particularly Alzheimer's disease (AD) and Parkinson's disease (PD). We pooled data with the weighted mean difference in sleep outcomes. To assess heterogeneity in results of individual studies, we used Cochran's Q statistic and the I (2) statistic. 9 RCTs were included in this research. We found that the treatment with exogenous melatonin has positive effects on sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI) in PD patients (MD: 4.20, 95 % CI: 0.92-7.48; P = 0.01), and by changes in PSQI component 4 in AD patients (MD: 0.67, 95 % CI: 0.04-1.30; P = 0.04), but not on objective sleep outcomes in both AD and PD patients. Treatment with melatonin effectively improved the clinical and neurophysiological aspects of rapid eye movement (REM) sleep behavior disorder (RBD), especially elderly individuals with underlying neurodegenerative disorders. This meta-analysis provided some evidence that melatonin improves sleep quality in patients with AD and PD, and melatonin can be considered as a possible sole or add-on therapy in neurodegenerative disorders patients with RBD.

[m-Nisodipine inhibited 5-HT-induced proliferation of rat PASMCs through Rho/ROCK signal pathway].

This paper is to report the exploration of the activation of Rho/ROCK signal pathway in 5-HT-induced proliferation of rat pulmonary artery smooth muscle cells (PASMCs) and the inhibitory effect of m-Nis on this pathway. PASMCs were cultured with the explant technique. MTT assay was used to explore the proliferation of PASMCs after 5-HT treated for different time and the intervening effect of m-Nis. RT-PCR and Western blot were used respectively to explore the mRNA expression of RhoA, ROCK1 and the protein expression of p-MYPT1 in 5-HT-treated PASMCs and intervening effect of m-Nis. The results of MTT assay suggested that 5-HT (1 µmol · L(-1)) treatment for 12-72 h significantly induced the proliferation of rat PASMCs (P<0.05 or P < 0.01), which were inhibited by m-Nis (1 x 10(-5), 1 x 10(-6), l x 10(-7), 1 x10(-8) mol · L(-1)) in dose-dependent manners (P < 0.05 or P < 0.01). Similarly, the mRNA expression of RhoA, ROCK1 and the protein expression of p-MYPT1 were also inhibited by m-Nis in different degrees (P < 0.05 or P < 0.01). Thus, the results of this study suggested that Rho/ROCK pathway played an important role in 5-HT-induced proliferation of rat PASMCs, m-Nis inhibited 5-HT-induced proliferation obviously, which may be related to the blockage of Rho/ROCK signal pathway.

Comparative efficacy and safety of OADs in management of GDM: network meta-analysis of randomized controlled trials.

OBJECTIVE: We conducted a network meta-analysis to evaluate the efficacy and safety of oral antidiabetic drugs (OADs) for gestational diabetes. DATA SOURCES: We searched PubMed, the Cochrane Library, ClinicalTrials.gov, and related reviews from inception to October 2014. STUDY SELECTION: We included randomized clinical trials comparing efficacy and safety between different OADs or OADs vs insulin in patients with gestational diabetes. DATA SYNTHESIS: We included 18 randomized clinical trials. Traditional and network meta-analyses were performed to compare different OADs or OADs vs insulin. Traditional meta-analyses confirmed that there was no significant difference in maternal fasting blood glucose or glycated hemoglobin levels in patients treated with insulin, metformin, and glyburide. Compared to insulin, metformin was associated with lower maternal weight gain (weighted mean difference [WMD], -1.49 kg; 95% confidence interval [CI], -2.26 to -0.31), shorter gestational age (WMD, -0.16 wk; 95% CI, -0.30 to -0.03), and increased incidence of premature birth (odds ratio [OR], 1.63; 95% CI, 1.07 to 2.48). Compared to insulin, glyburide was associated with higher neonatal birth weight (WMD, 130.68 g; 95% CI, 55.98 to 205.38), increased incidence of neonatal hypoglycemia (OR, 2.64; 95% CI, 1.59 to 4.38), and increased incidence of macrosomia (OR, 3.09; 95% CI, 1.59 to 6.04). Network meta-analysis revealed that glyburide was associated with higher maternal weight gain, higher neonatal birth weight, increased incidence of neonatal hypoglycemia, and increased incidence of macrosomia than was metformin. CONCLUSION: Both metformin and glyburide are suitable for use in the management of gestational diabetes because of good glycemic control. However, glyburide treatment is associated with increased risk of neonatal hypoglycemia, high maternal weight gain, high neonatal birth weight, and macrosomia.

Risk of fracture with thiazolidinediones: an updated meta-analysis of randomized clinical trials.

OBJECTIVE: The use of thiazolidinediones (TZDs) has been associated with increased fracture risk. We performed a comprehensive literature review and meta-analysis to estimate the risk of fractures with TZDs METHODS: We searched MEDLINE, Embase and the Cochrane Database, from inception to May 2014. We included all randomized trials that described the risk of fractures or changes in bone mineral density (BMD) with TZDs. We pooled data with odds ratios (ORs) for fractures and the weighted mean difference in BMD. To assess heterogeneity in results of individual studies, we used Cochran's Q statistic and the I(2) statistic. RESULTS: We included 24,544 participants with 896 fracture cases from 22 randomized controlled trials. Meta-analysis showed that the significantly increased incidence of fracture was found in women (OR=1.94; 95%CI: 1.60-2.35; P<0.001), but not in men (OR=1.02; 95%CI: 0.83-1.27; P=0.83). For women, the fracture risk was similar in rosiglitazone (OR=2.01; 95%CI: 1.61-2.51; P<0.001) and pioglitazone (OR=1.73; 95%CI: 1.18-2.55; P=0.005) treatment and appeared to be similar for participants aged <60years old (OR=1.89; 95%CI: 1.51-2.36; P<0.001) and aged ≥60years old (OR=2.07; 95%CI: 1.51-2.36; P<0.001). There was a non-significant trend towards increased risk of fractures in different cumulative durations of TZD exposure. TZD treatment was also associated with significant changes in BMD among women at the lumbar spine(weighted mean difference: -0.49%, 95%CI: -0.66% to -0.32%; P<0.001), the femoral neck (weighted mean difference: -0.34%, 95%CI: -0.51% to -0.16%; P<0.001) and the hip(weighted mean difference: -0.33%, 95%CI: -0.52% to -0.14%; P<0.001). CONCLUSIONS: Our results suggest that TZD treatment is associated with an increased risk of fractures in women, effects of rosiglitazone and pioglitazone are similar, fracture risk is independent of age and fracture risk has no clear association with duration of TZD exposure.

[Study on influence of processing methods on chemical constituents in Radix Paeoniae Alba].

OBJECTIVE: The influence of processing methods on chemical constituents in Radix Paeoniae Alba was observed. METHOD: A HPLC method was used for analyzing the changes of eight major constituents, namely gallic acid, paeoniflorin sulfonate, catechin, paeoniflorin sulfonate, albiflorin, paeoniflorin, benzoic acid, pentagalloylglucose and benzoylpaeoniflorin, with the three processing procedures of decorticating, boiling and fumigating by burning of sulphur. Analysis was performed using a Zorbax SB-C18 column (4.6 mm x 250 mm, 5 microm) with the mixture of acetonitrile (A) and 0.015% phosphoric acid solution as mobile phase in gradient mode. The detection wavelength was set at 230 nm and the column temperature was at 30 degrees C. RESULT: Except for gallic acid and pentagalloylglucose, the other constituents decreased during procedure of decorticating and boiling. Fumigating by burning of sulphur would produce a new compound, paeoniflorin sulfonate, which was a byproduct from the reaction of paeoniflorin with SO2. CONCLUSION: The significant changes were produced in chemical constituents of Radix Paeoniae Alba during three processing procedures. Therefore, the processing of Radix Paeoniae Alba should be strictly controlled and standardized.

Chiral selective effects of doxazosin enantiomers on blood pressure and urinary bladder pressure in anesthetized rats.

AIM: To study chiral selective effects of doxazosin enantiomers on blood pressure and urinary bladder pressure in anesthetized rats. METHODS: In anesthetized rats, the carotid blood pressure, left ventricular pressure of the heart and the urinary bladder pressure were recorded. RESULTS: Administration of S-doxazosin at 0.25, 2.5, 25, and 250 nmol/kg iv produced a dose-dependent decrease in blood pressure, but its depressor effect was significantly weaker than that induced by R-doxazosin and racemic-doxazosin (rac-doxazosin), and the ED(30) values (producing a 30% decrease in mean arterial pressure) of R-doxazosin, rac-doxazosin and S-doxazosin were 15.64, 45.93, and 128.81, respectively. Rac-doxazosin and its enantiomers administered cumulatively in anesthetized rats induced a dose-dependent decrease in the left ventricular systolic pressure and +/-dp/dt(max), and the potency order of the 3 agents was R-doxazosin > rac-doxazosin > S-doxazosin. Rac-doxazosin and its enantiomers decreased the vesical micturition pressure dose-dependently at 2.5, 25, and 250 nmol/kg, and the inhibitory potency among the 3 agents was not significantly different. CONCLUSION: S-doxazosin decreases the carotid blood pressure and left ventricular pressure of the heart less than R-doxazosin and rac-doxazosin, but its effect on the vesical micturition pressure is similar to R-doxazosin and rac-doxazosin, indicating that S-doxazosin has chiral selectivity between cardiovascular system and urinary system in anesthetized rats.

[New targets for drug therapeutics: receptors for purines and pyrimidines].

Endogenous nucleoside and nucleotide mediate a lot of functions via cell surface P receptors (receptors for purines and pyrimidines) in many organs. Nucleoside and nucleotide have protective roles in the events such as cancer, apoptosis, ischemia, wound healing, osteoporosis, drug toxicity, inflammation and pain. Moreover, the development of selective agonists and antagonists for P1, P2 receptors and P receptor subtypes may provide novel drugs in therapeutic strategies.