阿立哌唑治疗老年期首发精神分裂症临床分析

目的:比较阿立哌唑和氟哌啶醇治疗老年期首发精神分裂症的疗效和安全性.方法:将60例老年期首发精神分裂症患者随机分为阿立哌唑组和氟哌啶醇组,分别给予阿立哌唑和氟哌啶醇治疗,疗程8周.采用阳性与阴性症状量表(PANSS)评定疗效,用治疗中出现的症状量表(TESS)评定不良反应.结果:阿立哌唑与氟哌啶醇临床疗效差异无显著性,不良反应较轻.结论:阿立哌唑治疗老年期首发精神分裂症疗效好、安全性高,有利于长期巩固治疗.     

Dissociable Control of Impulsivity in Rats by Dopamine D2/3 Receptors in the Core and Shell Subregions of the Nucleus Accumbens

Previous research has identified the nucleus accumbens (NAcb) as an important brain region underlying inter-individual variation in impulsive behavior. Such variation has been linked to decreased dopamine (DA) D2/3 receptor availability in the ventral striatum of rats exhibiting spontaneously high levels of impulsivity on a 5-choice serial reaction time (5-CSRT) test of sustained visual attention. This study investigated the involvement of DA D2/3 receptors in the NAcb core (NAcbC) and the NAcb shell (NAcbS) in impulsivity. We investigated the effects of a DA D2/3 receptor antagonist (nafadotride) and a DA D2/3 partial agonist (aripiprazole) infused directly into either the NAcbC or NAcbS of rats selected for high (HI) and low (LI) impulsivity on the 5-CSRT task. Nafadotride increased significantly the level of impulsivity when infused into the NAcbS, but decreased impulsivity when infused into the NAcbC of HI rats. By contrast, intra-NAcb microinfusions of aripiprazole did not affect impulsivity. Systemic administration of nafadotride had no effect on impulsive behavior but increased the number of omissions and correct response latencies, whereas systemic injections of aripiprazole decreased impulsive and perseverative behavior, and increased the number of omissions and correct response latencies. These findings indicate an opponent modulation of impulsive behavior by DA D2/3 receptors in the NAcbS and NAcbC. Such divergent roles may have relevance for the etiology and treatment of clinical disorders of behavioral control, including attention-deficit hyperactivity disorder and drug addiction.     

Effects of DRD2 and CYP2D6 genotypes on delta EEG power response to aripiprazole in healthy male volunteers: a preliminary study

The aim of the present study was to evaluate the effects of polymorphisms in dopamine D2 receptor (DRD2) and cytochrome P450 (CYP) 2D6 genes on delta EEG power response to aripiprazole in healthy male volunteers. Seventeen volunteers were recruited according to the DRD2 Taq1A genotype, and separated into the following groups: homozygous wild-type (A2/A2, n = 7), heterozygous (A2/A1, n = 5) and homozygous variant-type (A1/A1, n = 5) groups. After enrollment in this study, they were genotyped for CYP2D6. The volunteers received single 10 mg oral doses of aripiprazole, in accordance with an open-label parallel group study design. Plasma levels of aripiprazole and its metabolite were determined and EEGs were obtained simultaneously. The pharmacodynamic parameter was absolute delta power in the Cz channel. The changes of delta power were not different according to DRD2 Taq1A genotypes. As to the CYP2D6 allele, the subjects had the following CYP2D6 genotypes: *10/*10 (n = 4), *1/*10 (n = 5), *1/*5 (n = 2), *1/*1 (n = 3), *2/*41 (n = 1), *2/*2 (n = 1), *2N/*10 (n = 1). Subjects exhibiting the *1/*5 and *1/*10 genotypes showed a trend toward high area under the plasma aripiprazole concentration-time curve (AUC), which was linearly related to area under the EEG response-time curve (AUEC). Our results demonstrate a need for further evaluation of the CYP2D6 genotypic effect on the pharmacodynamics of aripiprazole.     

HPLC分离阿立哌唑有关物质的方法学研究

 目的　建立阿立哌唑有关物质分离的HPLC。方法　采用反相C₈色谱柱,在室温条件下,以甲醇-1.5 %三乙胺(用醋酸调节pH5.6)(80∶20 )为流动相,流速为1mL·min^-1,检测波长为257nm,进样体积10μL。结果　阿立哌唑与中间体Ⅰ、中间体Ⅱ及其降解产物均能较好的分离,理论板数大于4200,且线性良好(r分别为0.9990,0.9996,0.9998)。中间体Ⅰ和中间体Ⅱ的最低检测限分别为3.0和3.3ng。日内、日间RSD分别为2.3%和3.1%。结论　本法可有效分离阿立哌唑有关物质及降解产物,灵敏度高 ,专属性强 ,可用于阿立哌唑有关物质及降解产物检查。     

多巴胺受体部分激动剂阿立哌唑药理作用与临床应用

阿立哌唑是一种多巴胺D2受体部分激动剂,对5-HT1A受体具有部分激动活性和5-HT2A受体阻滞活性.它可以改善精神分裂症阳性症状,而不引起运动障碍和催乳素增高,很少引起锥体外系反应.初步临床研究表明,阿立哌唑对精神分裂症有效,安全、耐受良好.     

RP-HPLC法测定阿立哌唑片剂中的阿立哌唑及有关物质

目的 :建立测定阿立哌唑片剂中阿立哌唑及有关物质的检测方法。方法 :采用反相高效液相色谱法 ,色谱柱为十八烷基硅烷键合硅胶柱 ,流动相为 0 .0 5mol·L-1 磷酸二氢钠水溶液 (含 1%三乙胺 ,磷酸调 pH至 5 .5 ) 乙腈 (5 0∶5 0 ) ,检测波长为2 17nm ,流速为 1.0ml·min-1 。结果 :阿立哌唑在 4.10 6～ 41.0 60mg·L-1 浓度范围内峰面积有良好线性关系 ,平均回收率为99 .90 %(n =9) ,重复性试验的相对标准偏差为 0 .82 %(n =6) ,最低检出限量为 0 .5 1ng ,有关物质与主药有较好的分离度。结论 :此法简单、专属性强、重现性好、结果准确可靠 ,适用于阿立哌唑片的质量控制。     

首发精神分裂症患者治疗前后细胞因子水平的变化

目的探讨阿立哌唑治疗前后首发Ⅰ型(以阳性症状为主)、Ⅱ型(以阴性症状为主)精神分裂症患者血浆细胞因子水平的变化。方法35例首发精神分裂症患者用阿立哌唑进行8周治疗,采用酶联免疫吸附法(ELISA)对治疗前后血浆白细胞介素(IL)-2和IL-4进行了检测。以18例健康志愿者为对照。结果①患者组治疗前血浆IL-2水平((3.27±1.41)ng/L)明显低于对照组((5.23±2.87)ng/L),有显著性差异(P<0.01)。②患者组治疗前血浆IL-4水平((3.06±2.19)ng/L)及治疗后((4.68±2.84)ng/L)均明显低于对照组((8.98±3.97)ng/L)(P均<0.01)。结论精神分裂症患者存在IL-2、IL-4介导的免疫功能紊乱。     

阿立哌唑与氯氮平治疗精神分裂症对照研究

目的：比较阿立哌唑与氯氮平治疗精神分裂症的临床疗效与安全性。方法：将精神分裂症患者100例随机分为阿立哌唑组与氯氮平组。疗程12周。采用阳性与阴性症状量表（PANSS）及治疗中出现的症状量表（TESS）、健康状况问卷（SF-36）评定疗效及不良反应。结果：两组治疗后PANSS评分均显著下降，两组问比较差异无显著性（P〉0．05）。不良反应发生率阿立哌唑组显著低于氯氮平组（P〈0．05）。结论：阿立哌唑治疗精神分裂症疗效与氯氮平相仿，不良反应少，是一种安全有效的抗精神病药。     

Open-label flexible-dose pilot study to evaluate the safety and tolerability of aripiprazole in patients with psychosis associated with Parkinson's disease.

Psychosis affects at least 5% to 8% of medication-treated patients with idiopathic Parkinson's disease (PD). Treatment options include reducing medications used for the treatment of PD-related motor symptoms or introducing an atypical antipsychotic drug. Only clozapine has been demonstrated to be efficacious and tolerated in double-blind controlled trials. This study evaluated the effect of aripiprazole, an atypical antipsychotic, on psychosis in PD in an open-label pilot study. Fourteen patients meeting entry criteria were started on aripiprazole 1 mg/day and titrated up to a maximum dose of 5 mg as needed. Subjects were evaluated on the Unified Parkinson's Disease Rating Scale (UPDRS) part III for motor function, the Neuropsychiatric Inventory (NPI), and the Brief Psychiatric Rating Scale (BPRS) for psychiatric response. Statistically significant improvement in mean BPRS and positive BPRS subscales occurred with open-label aripiprazole, but eight subjects discontinued the study due to worsened Parkinsonism (three), worsened psychosis (two), worsening of both (two), and lack of efficacy (one). While some patients had a favorable response, aripiprazole was associated with an exacerbation of motor symptoms. In this small study on psychosis in PD, aripiprazole did not appear promising.