Central components in the antinociceptive activity of dipyrone in mice

Dipyrone is classified as a nonsteroidal anti-inflammatory drug. It has analgesic, antipyretic and anti-inflammatory properties and exerts its analgesic effect via both peripheral and central action. Dipyrone at the dose of 250 and 500 mg/kg showed dose-dependent antinociceptive activity in the hot plate, tail flick tests to radiant heat and tail clip test and the writhing test induced by acetic acid in mice. The antinociceptive effects of dipyrone (500 mg/kg) were antagonized by naloxone (1, 2, 5 mg/kg) in the tail flick test to radiant heat and tail clip test and hot plate tests but not in the writhing test. Cyproheptadine (100 g/kg) decreased the antinociceptive effect of dipyrone. There was an increase in the antinociceptive effects of dipyrone (500 mg/kg) when combined with buspiron (0.5 mg/kg) in the tail flick test to radiant heat and tail clip test. The results provide evidence for a central antinociceptive effect of dipyrone antagonized by naloxone which suggests that its activity may also involve the serotoninergic system.     

盐酸丁螺环酮缓释片家兔体内血药浓度的测定

目的:建立盐酸丁螺环酮缓释片在家兔体内的血药浓度测定方法.方法:采用Nova-Pak C18柱(250mm×4.6mm,5μm),流动相为甲醇-乙腈-离子对试剂(10:50:40),检测波长为254nm.结果:缓释片中盐酸丁螺环酮在1～28ng·mL-1范围内呈良好的线性关系,r=0.999 5,平均回收率为98.45%,日内、日间精密度RSD均＜6%(n=6).结论:该测定方法准确、重现性好,简便、快速,适用于盐酸丁螺环酮缓释制剂研究的质量分析.     

以HPMC为骨架的盐酸丁螺环酮缓释片的制备

以HPMC单用或与卡波姆934p合用，制备盐酸丁螺环酮缓释片并进行体外释放度的测定。结果表明本品可持续释药24h，且加入卡波姆比单用HPMC为骨架具有更好的缓释效果。     

Inhibition of hepatobiliary transport as a predictive method for clinical hepatotoxicity of nefazodone.

Treatment with the antidepressant nefazodone has been associated with clinical idiosyncratic hepatotoxicty. Using membranes expressing human bile salt export pump (BSEP), human sandwich hepatocytes, and intact rats, we compared nefazodone and its marketed analogs, buspirone and trazodone. We found that nefazodone caused a strong inhibition of BSEP (IC(50) = 9 microM), inhibition of taurocholate efflux in human hepatocytes (IC(50) = 14 microM), and a transient increase in rat serum bile acids 1 h after oral drug administration. Buspirone or trazodone had no effect on biliary transport system. Nefazodone produced time- and concentration-dependent toxicity in human hepatocytes with IC(50) = 18 microM and 30 microM measured by inhibition of protein synthesis after 6 h and 24 h incubation, respectively. Toxicity was correlated with the amount of unmetabolized nefazodone. Partial recovery in toxicity by 24 h has been associated with metabolism of nefazodone to sulfate and glucuronide conjugates. The saturation of nefazodone metabolism resulted in sustained decrease in protein synthesis and cell death at 50 microM. The toxicity was not observed with buspirone or trazodone. Addition of 1-aminobenzotriazole (ABT), an inhibitor of CYP450, resulted in enhancement of nefazodone toxicity at 10 microM and was associated with accumulation of unmetabolized nefazodone. In human liver microsomes, ABT also prevented metabolism of nefazodone and formation of glutathione conjugates. We suggest that inhibition of bile acid transport by nefazodone is an indicator of potential hepatotoxicity. Our findings are consistent with the clinical experience and suggest that described methodology can be applied in the selection of nonhepatotoxic drug candidates.     

米氮平与丁螺环酮对照治疗广泛性焦虑疗效比较

目的:比较米氮平与丁螺环酮治疗广泛性焦虑的疗效和不良反应。方法:87例符合广泛性焦虑诊断标准的患者随机分成两组,试验组44例,口服米氮平15～45 mg·d~(-1);对照组43例,口服丁螺环酮15～40 mg·d~(-1),疗程均为4周。治疗前及治疗后1,2,4周末采用汉密尔顿焦虑量表(HAMA)、Zung焦虑自评量表(SAS)和临床总体印象量表(CGI)评定临床疗效,不良反应量表(TESS)评价不良反应。结果:试验组和对照组显效率分别为75·0%和76．6%(P＞0．05),两组不良反应比较无显著性差异(P＞0．05)。结论:米氮平治疗广泛性焦虑安全有效。     

Pharmacotherapy for generalized anxiety disorder in adult and pediatric patients: an evidence-based treatment review

Introduction: Generalized anxiety disorder (GAD) often begins during adolescence or early adulthood and persists throughout the lifespan. Randomized controlled trials support the efficacy of selective serotonin and selective serotonin norepinephrine reuptake inhibitors (SSRIs and SNRIs, respectively), as well as benzodiazepines, azapirones, anti-adrenergic medications, melatonin analogs, second-generation antipsychotics, kava, and lavender oil in GAD. However, psychopharmacologic treatment selection requires clinicians to consider multiple factors, including age, co-morbidity, and prior treatment.

Areas covered: The authors review the literature concerning pharmacotherapy for pediatric and adult patients with GAD with specific commentary on the efficacy and tolerability of selected agents in these age groups. The authors describe an algorithmic approach to the pediatric and adult patient with GAD and highlight considerations for the use of selected medications in these patients.

Expert opinion: In adults with GAD, SSRIs and SNRIs represent the first-line psychopharmacologic treatment while second-line pharmacotherapies include buspirone, benzodiazepines, SGAs, and pregabalin. In pediatric patients with GAD, SSRIs should be considered the first line pharmacotherapy and psychotherapy enhances antidepressant response.     

丁螺环酮与阿普唑仑治疗儿童广泛性焦虑症对照研究

目的　比较丁螺环酮与阿普唑仑治疗儿童广泛性焦虑症的临床疗效与不良反应。方法　将76例儿童广泛性焦虑症 患者随机分为丁螺环酮治疗组(研究组)与阿普唑仑治疗组(对照组),每组各38例,疗程8w;于治疗前及治疗第8w末采用汉 密尔顿焦虑量表、临床疗效总评量表评定临床疗效,第4、8周末采用副反应量表评定不良反应。疗效判定标准:汉密尔顿焦虑 量表减分率≥75%为痊愈,60～74%为显著进步,30～59%为进步,<30%为无效。结果　研究组有效率92.1%,对照组有效 率89.5%;治疗前后两组汉密尔顿焦虑量表总分、精神焦虑、躯体焦虑、临床疗效总评量表 GI、 SI评定均有极显著性差异(P <0.01);治疗后两组间精神焦虑因子有显著性差异(P<0.05),临床疗效总评量表 SI、临床疗效总评量表 GI比较均有极显 著性差异(P<0.01)。结论　丁螺环酮是治疗儿童广泛性焦虑症安全有效的药物。     

坦度螺酮与丁螺环酮治疗广泛性焦虑症的疗效和安全性比较研究

目的评价坦度螺酮治疗广泛性焦虑症的有效性和安全性。方法用随机化、双盲、双模拟、多中心、阳性药平行对照研究方法。共入组符合研究方案的病例236例,坦度螺酮组117例,丁螺环酮组119例。试验药的剂量为每日30-60mg,对照药的剂量为每日15-30 mg。结果两组病人的主要疗效指标HAMA评分在治疗结束时与基线比较均显著减低(P相似文献   

帕罗西汀与丁螺环酮对照治疗广泛性焦虑79例

目的:比较帕罗西汀与丁螺环酮治疗广泛性焦虑的疗效和不良反应.方法:79例广泛性焦虑患者随机分成2组,治疗组39例,口服帕罗西汀20～40mg·d-1;对照组40例,口服丁螺环酮15～40mg·d-1,2组疗程均为4周,治疗前及治疗后1,2,4周末采用汉密尔顿焦虑量表(HAMA)、焦虑自评量表(SAS)、临床总体印象量表(CGI)及不良反应量表(TESS)评定临床疗效和不良反应.结果:治疗组显效率为66.7%,对照组显效率为70.0%,2组疗效比较差异无显著性(P＞0.05).药物不良反应与对照组比较差异无显著性(P＞0.05).结论:帕罗西汀治疗广泛性焦虑安全有效.