Adsorptive stripping voltammetric methods for determination of aripiprazole

Anodic behavior of aripiprazole(ARP) was studied using electrochemical methods.Charge transfer,diffusion and surface coverage coefcients of adsorbed molecules and the number of electrons transferred in electrode mechanisms were calculated for quasi-reversible and adsorp-tion-controlled electrochemical oxidation of ARP at 1.15 V versus Ag/AgCl at pH 4.0 in Britton-Robinson buffer(BR) on glassy carbon electrode.Voltammetric methods for direct determination of ARP in pharmaceutical dosage forms and biological samples were developed.Linearity range is found as from 11.4 μM(5.11 mg/L) to 157 μM(70.41 mg/L) without stripping mode and it is found as from 0.221 μM(0.10 mg/L) to 13.6 μM(6.10 mg/L) with stripping mode.Limit of detection(LOD) was found to be 0.11 μM(0.05 mg/L) in stripping voltammetry.Methods were successfully applied to assay the drug in tablets,human serum and human urine with good recoveries between 95.0% and 104.6% with relative standard deviation less than 10%.

Effect of Aripiprazole on Methamphetamine-Induced Disruption of Latent Inhibition in Rats

Objectives: To elucidate the pharmacological profile of aripiprazole, we examined its ameliorating effect on the methamphetamine-induced disruption of latent inhibition (LI) in rats. Method: The effect was measured using a conditioned emotional response procedure. The conditioned stimulus was a tone (2.8 kHz, 90 dB), and the unconditioned stimulus was a mild foot shock delivered through a floor grid. The conditioning procedure was repeated five times. Results: Methamphetamine-induced (1.0 mg/kg, i.p.) disruption of LI was ameliorated by the administration of haloperidol (0.2 mg/kg, i.p.) and by a moderate dose of aripiprazole (0.3 mg/kg, i.p.) but not by a lower or higher dose (0.1 or 3.0 mg/kg, i.p.) of aripiprazole. However, immunohistochemical examination showed increased levels of c-Fos expression in the shell of the nucleus accumbens after the administration of haloperidol (0.2 mg/kg, i.p.) but not of aripiprazole (0.3 mg/kg, i.p.). Conclusions: It is suggested that aripiprazole has an ameliorating effect on methamphetamine-induced disruption of latent inhibition within only a marginal therapeutic window.

Effect of aripiprazole and olanzapine on the cognitive function in patients with schizophrenia

Objective:To observe the effect of aripiprazole and olanzapine on the cognitive function in patients with schizophrenia in order to provide a reference evidence for the clinical medication.Methods:A total of 60 patients with schizophrenia who were admitted in our hospital were included in the study and randomized into the treatment 1 group and treatment 2 group.The patients in the two groups were given aripiprazole and olanzapine,respectively.PANSS,WCST,DS,IGT,and EIRT were used to evaluate the disease condition and cognitive function before and after treatment in the two groups.Results:Comparision of PANSS scores and other various scores before treatment between the two groups was not significantly different(P>0.05);however,PANSS scores and other various scores after treatment were significantly reduced(P<0.05).Comparision of PANSS scores and other various scores after treatment between the two groups was not significantly different(P>0.05).DS,WCST,and IGT scores before treatment between the two groups was comparable(P>0.05),and those scores after treatment were significantly elevated(P<0.05).DS score after treatment in the treatment 2 group was significantly higher than that in the treatment 1 group(P<0.05).Comparison of WCST and IGT scores after treatment between the two groups was not significantly different(P>0.05).The four cognition scores of happiness,fear,anger,and disgust after treatment in the treatment 1 group were significantly elevated(P<0.05),while the cognition of happiness and sadness after treatment in the treatment 2 group was significantly elevated when compared with before treatment(P<0.05).The comparison of various scores before and after treatment between the two groups was not significantly different(P>0.05).Conclusions:Aripiprazole and olanzapine can improve the clinical symptoms and partial cognitive function in patients with schizophrenia,while aripiprazole can make a better effect on the work and memory.

Withdrawal seizure associated with high dosage of aripiprazole and fluoxetine: a case report

Aripiprazole, a third-generation antipsychotic, has been considered to have a high safety profile and rare withdrawal symptoms. We reported the case of a schizophrenic patient with a significant obsession, who was treated with a high dosage of aripiprazole and fluoxetine. Generalized tonic-clonic seizure occurred two days after abruptly stopping these two medications. Gradually tapering aripiprazole is suggested in clinical practice, especially when using a high dosage.

Intramuscular Diffusion Status of Risperidone and Aripiprazole Long Acting Injectable (LAI) by Ultrasonography

The aim of this study was to consider the characteristics of intramuscular diffusion status of risperidone and aripiprazole long acting injectable (LAI) by ultrasonography. Subjects were 40 adult subjects diagnosed with schizophrenia and treated with LAI [32 patients were risperidone LAI (RLAI) and 8 patients were aripiprazole LAI (ALAI)]. However, in this paper, only three cases (one RLAI case and 2 ALAI cases) were selected to illustrate the diffusion effects of both LAI. Dorsogluteal intramuscular (IM) injection sites were measured at prone position using the “double cross” method. Before LAI injection, the distance from the epidermis to the under-fascia (DEUF), and distance from the epidermis to the iliac bone (DEI) at the IM injection site were assessed by using ultrasonography: 1) the injection needle was inserted to the gluteus medius, and 2) observed the diffusion status within the muscle injected RLAI and ALAI were confirmed using the B-mode ultrasonography. Both RLAI and ALAI were depicted as high echogenicity with acoustic shadowing. It was considered that the diffusion states of LAIs by ultrasonography were important time course evaluations providing objective evidence.

Dissecting the novel abilities of aripiprazole: The generation of anti-colorectal cancer effects by targeting Gαq via HTR2B

Colorectal cancer(CRC)is a type of malignant tumor that seriously threatens human health and life,and its treatment has always been a difficulty and hotspot in research.Herein,this study for the first time reports that antipsychotic aripiprazole(Ari)against the proliferation of CRC cells both in vitro and in vivo,but with less damage in normal colon cells.Mechanistically,the results showed that5-hydroxytryptamine 2B receptor(HTR2B)and its coupling protein G protein subunit alpha q(Gaq)were highly distributed in CRC cells.Ari had a strong affinity with HTR2B and inhibited HTR2B downstream signaling.Blockade of HTR2B signaling suppressed the growth of CRC cells,but HTR2B was not found to have independent anticancer activity.Interestingly,the binding of Gaq to HTR2B was decreased after Ari treatment.Knockdown of Gaq not only restricted CRC cell growth,but also directly affected the antiCRC efficacy of Ari.Moreover,an interaction between Ari and Gaq was found in that the mutation at amino acid 190 of Gaq reduced the efficacy of Ari.Thus,these results confirm that Gaq coupled to HTR2B was a potential target of Ari in mediating CRC proliferation.Collectively,this study provides a novel effective strategy for CRC therapy and favorable evidence for promoting Ari as an anticancer agent.

阿立哌唑联合奥氮平对精神分裂症患者糖脂代谢及内分泌功能影响的研究

目的 探究阿立哌唑联合奥氮平对精神分裂症(SCZ)患者糖脂代谢及内分泌功能的影响。方法 将2020年1月至2023年1月芜湖市第四人民医院收治的100例SCZ患者纳入本次回顾性研究,根据治疗方法的不同分为联合组(n=50)和对照组(n=50)。联合组患者接受阿立哌唑联合奥氮平治疗,对照组患者接受奥氮平治疗,两组治疗周期均为8周。比较两组的临床疗效,治疗前、治疗8周后的阳性和阴性症状量表(PANSS)评分、糖脂代谢指标[空腹血糖、胰岛素抵抗指数(HOMA-IR)、甘油三酯、总胆固醇、低密度脂蛋白胆固醇(LDL-C)及高密度脂蛋白胆固醇(HDL-C)]、内分泌指标[催乳素及三碘甲状腺原氨酸(T3)、甲状腺素、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)]和不良反应发生情况。结果 联合组的总有效率为94.00%,优于对照组(80.00%),差异有统计学意义(P<0.05)。联合组治疗8周后的PANSS总评分为(59.17±8.92)分,显著低于对照组[(70.36±9.77)分],差异有统计学意义(P<0.05)。联合组治疗8周后的空腹血糖、甘油三酯、总胆固醇、LDL-C水平分别为(4.89±0.98)、(1.91±0.75)、(3.71±0.84)、(1.96±0.79) mmol/L,均显著低于对照组[(5.40±1.09)、(2.60±0.89)、(4.30±0.92)、(2.90±0.84) mmol/L],而HOMA-IR、HDL-C水平分别为1.56±0.18、(5.47±0.83) mmol/L,均显著高于对照组[1.34±0.14、(4.92±0.79) mmol/L],差异均有统计学意义(P<0.05)。联合组治疗8周后的催乳素为(16.89±8.01) ng/mL,显著低于对照组[(51.96±9.32)ng/mL],差异有统计学意义(P<0.05),而两组的T3、甲状腺素、FT3和FT4水平比较,差异均无统计学意义(P>0.05)。两组的不良反应发生率比较,差异均无统计学意义(P>0.05)。结论 阿立哌唑联合奥氮平治疗SCZ的疗效显著,可有效改善患者的糖脂代谢,调节内分泌激素水平,且安全性良好。

维生素D_(3)联合rTMS、阿立哌唑治疗精神分裂症效果及对血清25-(OH)D_(3)、BDNF、认知损伤指标的影响

目的 探讨维生素D_(3)联合重复经颅磁刺激(rTMS)、阿立哌唑治疗精神分裂症效果及对血清25-羟基维生素D_(3)[25-(OH)D_(3)]、脑源性神经生长因子(BDNF)、认知损伤指标的影响。方法 选取2022年1月—2023年3月收治的精神分裂症104例,根据治疗方法不同将其分为观察组和对照组2组各52例。观察组采用维生素D_(3)联合rTMS、阿立哌唑治疗,对照组采用rTMS联合阿立哌唑治疗。比较2组治疗后临床效果,治疗前后精神病性症状[阳性与阴性症状量表(PANSS)评分]、认知损伤指标[胰岛素样生长因子-1(IGF-1)、神经细胞黏附分子(NCAM)、半乳糖凝集素-3(Galectin-3)]、脑电图及星形胶质源性蛋白(S100B)、25-(OH)D_(3)、BDNF水平,以及治疗期间不良反应发生情况。结果 观察组总有效率94.23%(49/52)高于对照组80.77%(42/52)(P<0.05)。治疗后,观察组PANSS各项评分、α波幅及血清S100B水平低于对照组,θ波幅及血清IGF-1、NCAM、Galectin-3、25-(OH)D_(3)、BDNF水平高于对照组(P<0.05,P<0.01)。治疗期间,2组不良反应发生率比较差异无统计学意义(P>0.05)。结论 维生素D_(3)联合rTMS、阿立哌唑治疗精神分裂症可提高临床效果,减轻精神病性症状,改善脑电异常,降低认知功能损伤指标水平。

阿立哌唑联合认知行为治疗慢性精神分裂症的临床效果

目的 观察阿立哌唑联合认知行为治疗慢性精神分裂症的临床效果,为精神科治疗工作提供参考。方法 选取2019年9月—2020年8月山东省临沂市精神卫生中心精神科收治的慢性精神分裂症患者84例,以随机数字表法分为观察组和对照组,每组42例。对照组患者给予阿立哌唑治疗,观察组患者则在对照组基础上实施认知行为治疗,2组均治疗8周进行疗效评价。比较2组患者治疗效果,治疗前后精神状况、认知功能、生活质量评分及不良反应。结果 观察组患者治疗总有效率为95.24%,高于对照组的78.57%(χ^(2)=5.126,P=0.024)。治疗8周后,2组患者阳性与阴性症状量表(PANSS)中阳性症状、阴性症状评分较治疗前均明显降低,且观察组低于对照组(P<0.05或P<0.01);观察组患者威斯康辛卡片分类测验(WCST)中总正确数、完成分类数高于对照组及治疗前,随机错误数、持续错误数低于对照组及治疗前(P<0.05或P<0.01);2组患者精神分裂症生活质量量表(SQLS)评分较治疗前降低,且观察组低于对照组(P均<0.01)。观察组与对照组不良反应总发生率比较差异无统计学意义(11.90%vs. 9.52%,χ^(2)=0.124,P=0.724)。结论 阿立哌唑联合认知行为治疗慢性精神分裂症效果好,有助于改善患者症状、认知功能与生活质量,且患者用药安全性高。

重复经颅磁刺激结合阿立哌唑对精神分裂抑郁症患者认知损害、抑郁程度及症状的改善作用

目的分析重复经颅磁刺激结合阿立哌唑干预后,对精神分裂抑郁症患者认知损害、抑郁程度及精神病症状严重程度的改善作用。方法选取洛阳市第五人民医院精神十二科于2021年5月至2022年5月收治的精神分裂抑郁症患者,符合纳入和排除标准的合计200例。将上述患者按照随机数字表法分为对照组(阿立哌唑,100例)、观察组(阿立哌唑联合重复经颅磁刺激,100例)。观察疗效、认知损害、抑郁、精神病症状严重程度评分、神经递质水平及不良反应。结果观察组治疗总有效率高于对照组,差异有统计学意义(P<0.05)。两组干预前的认知功能各项指标评分差异无统计学意义(P>0.05),干预6周,两组认知功能评分均有所提升,且观察组高于对照组,差异有统计学意义(P<0.05)。两组干预前的抑郁情况差异无统计学意义(P>0.05),干预6周后,两组的抑郁评分均有所降低,且观察组低于对照组,差异有统计学意义(P<0.05)。两组干预前精神病症状的严重程度差异无统计学意义(P>0.05),干预6周后,两组精神病症状的严重程度均有所降低,观察组精神病症状的严重程度评分低于对照组,差异有统计学意义(P<0.05)。两组患者干预前的神经递质水平差异无统计学意义(P>0.05),干预6周后,神经递质水平均升高,且观察组变化幅度大于对照组,差异有统计学意义(P<0.05)。两组头痛、恶心、失眠的总发生率差异无统计学意义(P>0.05)。结论重复经颅磁刺激结合阿立哌唑能够改善精神分裂抑郁症患者的认知损害,减轻抑郁程度及精神病症状的严重程度,还能够调节神经递质水平,治疗效果良好,并且不会增加不良反应的发生率,该治疗策略安全有效。

阿立哌唑联合奥氮平治疗住院男性精神分裂症患者的效果及对代谢综合征的影响

背景 精神分裂症及抗精神病药物使用均可能导致患者发生代谢综合征(MS),增加心血管疾病的发生风险,不利于疾病预后。有效预防或降低精神分裂症患者伴发MS的风险至关重要。目的 探讨阿立哌唑联合奥氮平治疗男性精神分裂症的效果及其对患者MS的影响,以期为男性精神分裂症患者抗精神病药物的选择提供参考。方法 连续选取2023年2月—6月在梅州市第三人民医院住院治疗的、符合《国际疾病分类(第10版)》(ICD-10)精神分裂症诊断标准的80例男性患者。采用随机数表法分为研究组(阿立哌唑联合奥氮平口服)与对照组(奥氮平单药口服)各40例,两组均连续用药6周。治疗前,两组均接受阳性和阴性症状量表(PANSS)评定和MS相关指标[空腹血糖(FPG)、糖化血红蛋白(HbA1c)、体质量指数(BMI)、腰臀比(WHR)及血脂水平]、血清S100钙结合蛋白B(S100B)以及超敏C反应蛋白(hs-CRP)水平检测,于治疗第2、4、6周末再次行PANSS评定,于治疗第2周和第6周末进行临床疗效总评量表(CGI)评定,治疗第6周末再次进行MS相关指标、S100B以及hs-CRP水平检测及副反应量表(TESS)评定。结果 两组PANSS评分的组别效应、时间效应及组别与时间的交互效应均有统计学意义(F=18.092、634.780、2.917,P<0.05或0.01)。两组CGI评分的组别效应和时间效应均有统计学意义(F=20.492、99.190,P均<0.01)。治疗第6周末,研究组HbA1c和甘油三酯(TG)水平均低于对照组(t=-3.495、-3.293,P均<0.05)。治疗第6周末,研究组hs-CRP水平低于对照组(t=-3.916,P<0.05)。研究组TESS评分低于对照组(t=-4.684,P<0.01)。结论 与奥氮平单药治疗相比,阿立哌唑联合奥氮平可能更有助于改善男性精神分裂症患者的精神病性症状,且对MS相关指标的影响更小。

阿立哌唑对男性首发精神分裂症患者性激素、心肌酶谱及勃起功能的影响

目的分析阿立哌唑对男性首发精神分裂症(SCH)患者性激素、心肌酶谱及勃起功能的影响。方法回顾性收集2023年1月至2024年1月秦皇岛市九龙山医院收治的120例男性首发SCH患者的临床资料。根据治疗方法不同分为利培酮组(n=60)、阿立哌唑组(n=60)。利培酮组患者口服利培酮,初始给药量1 mg/d,1~2周给药剂量逐渐增加至6 mg/d,1次/d。阿立哌唑组患者口服阿立哌唑,初始给药量5 mg/d,治疗2~3周剂量增加至30 mg/d,1次/d。比较两组疗效,对比两组治疗前和治疗2个月后空腹血糖、总胆固醇、甘油三酯、性激素(睾酮、雌二醇、黄体生成素)、心肌酶[肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)]变化、国际勃起功能指数-5问卷(IIEF-5)评分变化,比较两组药物不良反应发生情况。结果治疗2个月后,两组睾酮、雌二醇、黄体生成素水平均较治疗前明显升高,阿立哌唑组的睾酮、雌二醇、黄体生成素水平分别为(4.89±0.47)ng/mL、(36.27±3.74)ng/mL、(6.21±0.68)mU/mL,均明显高于利培酮组[(4.05±0.41)ng/mL、(32.22±3.36)ng/mL、(5.11±0.52)mU/mL],差异均有统计学意义(P<0.05)。治疗2个月后,两组CK、CK-MB、LDH水平均较治疗前明显降低,阿立哌唑组CK、CK-MB、LDH水平分别为(111.34±11.23)、(19.24±1.95)、(147.66±15.24)U/L,均明显高于利培酮组[(101.22±10.56)、(16.32±1.85)、(121.85±13.26)U/L],差异均有统计学意义(P<0.05)。治疗2个月后,利培酮组的性信心、性驱动、性高潮满意度、性唤起、阴茎勃起能力评分均较治疗前明显降低,阿立哌唑组性信心、性驱动、性高潮满意度、性唤起、阴茎勃起能力评分分别为(3.75±0.38)、(3.93±0.39)、(3.85±0.38)、(4.08±0.41)、(3.97±0.40)分,均明显高于利培酮组[(2.29±0.22)、(2.41±0.25)、(2.07±0.19)、(2.71±0.28)、(2.20±0.22)分],差异均有统计学意义(P<0.05)。结论阿立哌唑对男性首发SCH患者疗效明确,有效调节患者性激素水平,减轻心肌损伤、勃起功能障碍等。

阿立哌唑联合无抽搐电休克治疗难治性精神分裂症的临床效果观察

目的研究阿立哌唑联合无抽搐电休克治疗难治性精神分裂症患者的临床效果。方法86例难治性精神分裂症患者,以随机数字表法分为试验组及对照组,每组43例。两组均行阿立哌唑药物治疗,试验组在此基础上行无抽搐电休克治疗。比较两组治疗效果、症状评分(阳性症状、阴性症状、一般精神病理评分)、血清神经营养因子[脑源性神经营养因子(BDNF)、神经生长因子(NGF)、神经营养因子-3(NT-3)]、血清炎症因子[白细胞介素-4(IL-4)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)]、不良反应发生率。结果试验组的治疗优良率69.77%高于对照组的41.86%(P<0.05)。治疗后,两组的阳性症状、阴性症状、一般精神病理评分及总分低于治疗前,且试验组的阳性症状、阴性症状、一般精神病理评分及总分分别为(15.51±2.64)、(13.62±2.88)、(22.53±5.82)、(51.66±6.78)分,低于对照组的(20.21±5.47)、(18.69±4.75)、(27.66±7.82)、(66.56±9.24)分(P<0.05)。治疗后,两组的BDNF、NGF、NT-3水平高于治疗前,且试验组的BDNF(14.05±2.56)μg/L、NGF(46.77±9.21)μg/L、NT-3(170.82±22.61)pg/ml高于对照组的(11.18±1.97)μg/L、(38.69±8.41)μg/L、(151.63±20.74)pg/ml(P<0.05)。治疗后,两组的IL-4水平高于治疗前,IL-6、IL-1β水平低于治疗前,且试验组的IL-4(11.35±3.58)pg/ml高于对照组的(9.52±2.64)pg/ml,IL-6(30.31±3.64)pg/ml、IL-1β(26.85±3.62)pg/ml低于对照组的(41.49±5.73)、(35.85±4.86)pg/ml(P<0.05)。两组的不良反应发生率比较差异无统计学意义(P>0.05)。结论阿立哌唑联合无抽搐电休克治疗难治性精神分裂症可显著提高患者治疗效果,在积极减轻症状的同时对调整炎症平衡、增强神经营养亦有良好作用,具有较好的安全性,值得研究推广。

涤痰化瘀理神方治疗精神分裂症疗效观察及对血清BDNF水平的影响

目的:观察涤痰化瘀理神方治疗精神分裂症的临床疗效及对血清脑源性神经营养因子(BDNF)水平的影响。方法:按随机数字表法将94例精神分裂症患者分为对照组和研究组各47例。对照组给予奥氮平片、阿立哌唑片治疗,研究组在对照组基础上加用涤痰化瘀理神方治疗。治疗3个月后,比较2组临床疗效,以及治疗前后阳性与阴性症状量表(PANSS)评分、蒙特利尔认知评估量表(MoCA)评分及血清BDNF水平。结果:研究组总有效率为91.49%,对照组为76.60%,2组比较,差异有统计学意义(P<0.05)。治疗后,2组PANSS中阴性症状评分、阳性症状评分、一般病理评分及总分均较治疗前降低(P<0.05),且研究组上述各项评分均低于对照组(P<0.05)。治疗后,2组MoCA量表中视空间与执行功能、定向、记忆、语言、注意、命名、抽象评分及总分均较治疗前升高(P<0.05),且研究组上述各项评分均高于对照组(P<0.05)。治疗后,2组血清BDNF水平均较治疗前升高(P<0.05),且研究组血清BDNF水平高于对照组(P<0.05)。结论:涤痰化瘀理神方辅助治疗精神分裂症有助于提高临床疗效,改善患者精神行为症状及认知功能,有效调节脑源性神经营养因子水平。

Preparation of aripiprazole-poly(methyl vinyl ether-co-maleic anhydride)nanocomposites via supercritical antisolvent process for improved antidepression therapy

Aripiprazole(ARI),a second-generation atypical antipsychotic drug approved for schizophrenia treatment,shows good efficacy against depression.However,the poorly aqueous solubility of ARI leads to low bioavailability and increased dose-related side effects,seriously limiting its application in pharmaceutics.Herein,we demonstrated the fabrication of ARI and poly(methyl vinyl etherco-maleic anhydride)(PVMMA)composite nanoparticles(PA NPs)using the supercritical antisolvent(SAS)process for enhancing its water-solubility and curative anti-depressant effects.Initially,the optimal experimental conditions(ARI/PVMMA mass ratio of 1:6,pressure of 10MPa,and solution flow rate of 0.75ml min^(-1))were determined by a 23 factorial experimental design,resulting in the PA NPs with an excellent particle morphology.In vitro cell experiments showed that PA NPs significantly inhibited the inflammatory response caused by the microglia activation induced by lipopolysaccharide(LPS).Similarly,mice behavioral tests demonstrated that PA NPs significantly improved LPS-induced depression-like behavior.Importantly,compared with free ARI,the LPS-induced activation of microglia in the mouse brain and the expression of inflammatory factors in serum were significantly reduced after treatment with PA NPs.Together,the innovative PA NPs designed by SAS processmight provide a candidate for developing new ARI-based nano-formulations.