Who can benefit more from its twelve-week treatment:A prospective cohort study of blonanserin for patients with schizophrenia

BACKGROUND Blonanserin(BNS)is a well-tolerated and effective drug for treating schizophrenia.AIM To investigate which types of patients would obtain the most benefit from BNS treatment.METHODS A total of 3306 participants were evaluated in a 12-week,prospective,multicenter,open-label post-marketing surveillance study of BNS.Brief psychiatric rating scale(BPRS)scores were calculated to evaluate the effectiveness of BNS,and its safety was assessed with the incidence of adverse drug reactions.Linear regression was used to screen the influencing factors for the reduction of BPRS total score,and logistic regression was used to identify patients with a better response to BNS.RESULTS The baseline BPRS total score(48.8±15.03)decreased to 27.7±10.08 at 12 weeks(P<0.001).Extrapyramidal symptoms(14.6%)were found to be the most frequent adverse drug reactions.The acute phase,baseline BPRS total score,current episode duration,number of previous episodes,dose of concomitant antipsychotics,and number of types of sedative-hypnotic agents were found to be independent factors affecting the reduction of BPRS total score after treatment initiation.Specifically,patients in the acute phase with baseline BPRS total score≥45,current episode duration<3 months,and≤3 previous episodes derived greater benefit from 12-week treatment with BNS.CONCLUSION Patients in the acute phase with more severe symptoms,shorter current episode duration,fewer previous episodes,and a lower psychotropic drug load derived the greatest benefit from treatment with BNS.

Case Report: Augmentation with Blonanserin for a Schizophrenia Patient with Insufficient Response to Clozapine

Background: Clozapine is the most efficacious among antipsychotics for patients with schizophrenia. Nevertheless, clozapine is not effective in more than about 50% of treatment refractory schizophrenia patients, and several pharmacological strategies are used to augment it. Several reviews including meta-analyses have been published, but the efficacy of augmentation therapy for clozapine-resistant patients is not adequately supported. Though there is a weak connection between the oral dose and plasma concentration of clozapine, there is no report of augmentation therapy considering the plasma concentration of clozapine. Blonanserin is reported to be effective in treatment of both positive and negative symptoms of schizophrenia and well tolerated. Methods: We obtained consent to evaluate clinical presentations and clozapine plasma concentrations at the Okayama Psychiatric Medical Center and had not identified the individual for ethical reasons. This is a case report. Results: This case fulfilled the diagnostic criteria of neuroleptic-induced dopamine supersensitivity psychosis. Monotherapy with blonanserin was not effective, but augmentation of blonanserin with clozapine was effective and well tolerated by a clozapine-resistant schizophrenia patient. Conclusion: Because clozapine may ameliorate dopamine supersensitivity psychosis, the addition of blonanserin to clozapine may be effective even if monotherapy with blonanserin was not.

Possible effect of blonanserin on gambling disorder:A clinical study protocol and a case report

BACKGROUND Gambling disorder is characterized by excessive and recurrent gambling and can have serious negative social consequences.Although several psychotherapeutic and pharmacological approaches have been used to treat gambling disorder,new treatment strategies are needed.Growing evidence suggests that dopamine D3 receptor plays a specific role in the brain reward system.AIM To investigate if blonanserin,a dopamine D3 receptor antagonist,would be effective in reducing gambling impulses in patients with gambling disorder.METHODS We developed a study protocol to measure the efficacy and safety of blonanserin as a potential drug for gambling disorder,in which up to 12 mg/d of blonanserin was prescribed for 8 wk.RESULTS A 37-year-old female patient with gambling disorder,intellectual disability,and other physical diseases participated in the pilot study.The case showed improvement of gambling symptoms without any psychotherapy.However,blonanserin was discontinued owing to excessive saliva production.CONCLUSION This case suggests that blonanserin is potentially an effective treatment for patients with gambling disorder who resist standard therapies,but it also carries a risk of adverse effects. Further studies are needed to confirm the findings.

布南色林对精神分裂症患者泌乳素水平及认知功能的影响

目的 探讨布南色林对精神分裂症患者泌乳素水平及认知功能的影响。方法 将60例伴高泌乳素血症的精神分裂症患者随机分为研究组(换用布南色林治疗4周)和对照组(维持原治疗方案),各30例。比较两组患者在入组时(基线期)及治疗后的泌乳素水平及蒙特利尔认知评估量表(MoCA)、阳性与阴性症状量表(PANSS)、锥体外系副反应量表(RSESE)、亚利桑那性体验量表(ASEX)评分。结果 治疗后,研究组患者PANSS总分及各因子分、泌乳素水平均较基线期下降(P<0.05或0.01),MoCA总分及视空间与执行、延迟回忆、定向等因子分均较基线期升高(P<0.05或0.01);对照组患者PANSS总分及各因子分均较基线期下降(P<0.05或0.01)。经校正的治疗后两组各指标比较,研究组患者PANSS总分及阴性症状因子分、泌乳素、ASEX评分均低于对照组(P<0.05或0.01),MoCA总分及视空间与执行、注意、延迟回忆、定向因子分均高于对照组(P<0.05或0.01)。结论 将泌乳素高风险的抗精神病药物换为布南色林后,伴高泌乳素血症的精神分裂症患者泌乳素水平下降,认知损害程度、精神症状和性功能均有改善,锥体外系反应无显著变化。

布南色林对早期利培酮治疗无应答首发精神分裂症患者神经因子的影响

目的:探讨布南色林对早期利培酮治疗无应答首发精神分裂症患者神经递质表达的影响。方法:选取本院2022年1月至2022年12月期间住院治疗的120例早期行利培酮单药治疗无应答的首发精神分裂症患者作为研究对象,对照组和研究组各60例。对照组给予氯氮平治疗,研究组给予布南色林治疗,疗程3个月。比较两组患者阳性和阴性精神症状评定量表(positive and negative syndrome scale,PANSS)评分、生活质量综合评定问卷(generic quality of life inventory-74,GQOLI-74)评分、血清脑源性神经营养因子(brain derived neurotrophic factor,BDNF)浓度、血清S100β蛋白、神经元特异性烯醇化酶(neuron specific enolase,NSE)以及神经调节蛋白1(nerve regulatory protein 1,NRG1)水平,记录患者出现的药物不良反应。结果:治疗3个月后,两组PANSS评分均较治疗前有所下降,且研究组PANSS评分更低;两组躯体功能、社会功能、心理功能评分均高于治疗前,且研究组评分高于对照组,差异均有统计学意义(P均<0.05)。治疗3个月后,两组血清BDNF以及NRG1水平高于治疗前,且研究组高于对照组;两组S100β、NSE水平低于治疗前,且研究组低于对照组,差异均有统计学意义(P均<0.05)。两组均未发生严重不良反应事件。结论:布南色林可有效改善早期利培酮单药治疗无应答首发精神分裂症患者的症状,且能够合理调节患者神经递质表达,改善患者认知功能。

Effect of isopropyl myristate on the viscoelasticity and drug release of a drug-in-adhesive transdermal patch containing blonanserin

The purpose of this study was to investigate the effect of isopropyl myristate (IPM), a penetration enhancer, on the viscoelasticity and drug release of a drug-in-adhesive transdermal patch containing blonanserin. The patches were prepared with DURO-TAK (R) 87-2287 as a pressure-sensitive adhesive (PSA) containing 5% (w/w) of blonanserin and different concentrations of IPM. An in vitro release experiment was performed and the adhesive performance of the drug-in-adhesive patches with different concentrations of IPM was evaluated by a rolling ball tack test and a shear-adhesion test. The glass transition temperature (T-g) and rheological parameters of the drug-in-adhesive layers were determined to study the effect of IPM on the mechanical properties of the PSA. The results of the in vitro release experiment showed that the release rate of blonanserin increased with an increasing concentration of IPM. The rolling ball tack test and shear-adhesion test showed decreasing values with increasing IPM concentration. The results were interpreted on the basis of the IPM-induced plasticization of the PSA, as evidenced by a depression of the glass transition temperature and a decrease in the elastic modulus. In conclusion, IPM acted as a plasticizer on DURO-TAK (R) 87-2287, and it increased the release of blonanserin and affected the adhesive properties of the PSA. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND

布南色林临床应用进展

第二代(非典型)抗精神病药布南色林对多巴胺D2、D3受体和5-羟色胺2A(5 Hydroxytryptami ne 2A receptor,5-HT2A)受体均有较高亲和力,而对肾上腺素α1、5-HT2C、组胺H1、毒蕈碱M1和M3等受体亲和力较低。近10年临床研究显示布南色林不仅对精神分裂症的阳性症状、阴性症状均有较好疗效,同时还具有抗焦虑抗抑郁作用,对患者的认知及其社会功能的改善疗效优越。

布南色林对女性精神分裂症患者短期内泌乳素水平及月经的影响研究

目的探讨女性精神分裂症患者采用布南色林的疗效及对泌乳素水平和月经的影响。方法采用随机数字表法将2021年1月至2022年1月赣州市第三人民医院收治的女性精神分裂症患者120例分为三组,各40例。对照1组采用奥氮平治疗,对照2组采用利培酮治疗,观察组采用布南色林治疗,均治疗8周。比较三组治疗效果、性激素、月经情况及不良反应。结果三组治疗总有效率比较,差异无统计学意义(P>0.05)。治疗后,对照1组、对照2组泌卵泡生成激素(FSH)、黄体生成激素(LH)及雌二醇(E2)水平均比治疗前低,泌乳素(PRL)、睾酮(T)水平均比治疗前高,差异有统计学意义(P<0.05);观察组PRL、FSH、LH、T、E2水平与治疗前比较,差异无统计学意义(P>0.05);观察组月经延迟发生率比对照1组、对照2组低,差异有统计学意义(P<0.05);三组闭经发生率比较,差异无统计学意义(P>0.05)。观察组不良反应发生率比对照1组、对照2组低,差异有统计学意义(P<0.05)。结论女性精神分裂症患者采用布南色林治疗效果满意,对PRL及月经影响小,并可减少不良反应发生。

几种新型抗精神病药介绍

综合有关文献,介绍阿利哌唑、Blonanserin(AD5423)、齐哌西酮、SM13496、利培酮长效注射剂等新型抗精神病药。

布南色林和鲁拉西酮改善精神分裂症患者认知功能的机制及临床应用研究进展

认知功能障碍是精神分裂症常见症状之一,主要表现为抽象思维、记忆、注意等方面的障碍。认知功能的改善对患者疾病康复、社会功能恢复具有至关重要的意义。近来研究表明新型非典型抗精神病药物布南色林和鲁拉西酮具有独特的受体作用机制,有望使患者认知功能障碍得到更好的改善。笔者从精神分裂症患者认知功能障碍的病因机制入手,综述布南色林和鲁拉西酮改善精神分裂症患者认知功能的作用机制;介绍两种药物的临床应用进展,以便更好地指导临床用药,为进一步研究提供新方向。

布南色林的合成

对氟苯甲酸甲酯与乙腈缩合得对氟苯甲酰乙腈,在多聚磷酸中反应制得3-(4-氟苯基)-3-氧代丙酰胺,与环辛酮环合得到的4-(4-氟苯基)-5,6,7,8,9,10-六氢环辛烷并[b]吡啶-2(1H)-酮,再用苯膦酰二氯化物氯化、与N-乙基哌嗪亲核取代,得抗精神病药布南色林,总收率约42%。

布南色林治疗精神分裂症的临床应用中日专家建议

第二代(非典型)抗精神病药布南色林对多巴胺D_(2)、D_(3)受体和5-HT_(2A)受体均有较高亲和力,而对肾上腺素α_(1)、5-HT_(2c)、组胺H_(1)、毒蕈碱M_(1)和M_(3)等受体亲和力较低。多项短期和长期临床研究显示:该药对精神分裂症的阳性症状、阴性症状均有较好疗效,并改善患者的部分认知症状和社会功能。本文在循证证据和多位中日专家临床用药经验基础上撰写,希望为临床精神科医生提供用药参考,帮助精神分裂症患者早日康复,回归社会。

布南色林片在中国健康志愿者体内的药代动力学

为了研究布南色林片单次给药后的中国健康志愿者体内的药代动力学，30例健康志愿者单次口服4mg、8mg和12mg布南色林片后，采集60h内动态血标本，采用LC—MS／MS测定血浆中布南色林的浓度，并用DAS3．2．4软件对试验数据进行处理，计算药代动力学参数。单次口服4mg、8mg和12mg布南色林片的主要药代动力学参数cmax分别为（539．61±388．74）、（1190．39±736．51）和（1637．34±481．45）ng／L，tmax分别为（1．00±0．47）、（1．38±0．79）和（1．43±0．94）h，t1/2分别为（12．05±3．49）、（14．76±3．78）和（13．68±3．92）h，AUC0-60h分别为（4692．21±3041．75）、（7964．42±3988．07）和（9648．22±2565．07）ng·h／L，AUC0-∞分别为（5060．91±3146．10）、（8547．61±4209．87）和（9986．15±2659．51）ng·h／L。可见，在4～12mg给药剂量范围内，布南色林片的主要药代动力学参数的cmax、AUC0-60h、AUC0-∞与剂量呈正相关。

顶空气相色谱法同时测定布南色林原料药中9种有机溶剂的残留量

目的:建立同时测定布南色林原料药中甲醇、乙醇、异丙醇、乙腈、二氯甲烷、正己烷、乙酸乙酯、四氢呋喃和甲苯9种有机溶剂残留量的方法。方法:采用顶空气相色谱法。色谱柱为DB-624毛细管柱,程序升温,进样口温度为150℃,检测器为氢火焰离子化检测器,温度为250℃,载气为高纯氮气,载气流速为2.8 m L/min,分流比为1∶1,顶空进样量为1 m L,顶空加热温度为90℃,平衡时间为35 min。结果:甲醇、乙醇、异丙醇、乙腈、二氯甲烷、正己烷、乙酸乙酯、四氢呋喃和甲苯检测质量浓度线性范围分别为6~1 500μg/m L(r=0.999 8)、10~2 500μg/m L(r=0.999 9)、10~2 500μg/m L(r=0.999 8)、0.82~205μg/m L(r=0.999 4)、1.2~300μg/m L(r=0.999 5)、0.58~145μg/m L(r=0.999 4)、10~2 500μg/m L(r=0.999 9)、1.44~360μg/m L(r=0.999 6)、1.78~445μg/m L(r=0.999 5);定量限分别为17.71、6.02、3.17、7.45、1.53、0.69、0.93、1.01、0.22μg/m L,检测限分别为5.89、1.90、1.05、2.48、0.51、0.23、0.31、0.33、0.07μg/m L;精密度、稳定性试验的RSD<3.0%,重复性试验中只检出异丙醇,RSD=2.1%;加样回收率分别为96.67%~102.66%(RSD=1.9%,n=9)、96.00%~101.83%(RSD=1.9%,n=9)、97.17%~101.50%(RSD=1.4%,n=9)、96.97%~102.44%(RSD=2.2%,n=9)、95.83%~103.33%(RSD=2.5%,n=9)、95.83%~100.28%(RSD=1.9%,n=9)、98.17%~101.25%(RSD=1.0%,n=9)、96.55%~102.30%(RSD=1.9%,n=9)、96.30%~102.22%(RSD=1.8%,n=9)。结论:该方法操作简单、快速,结果准确,可用于布南色林原料药中甲醇、乙醇、异丙醇、乙腈、二氯甲烷、正己烷、乙酸乙酯、四氢呋喃和甲苯9种有机溶剂残留量的同时测定。

布南色林对H_2O_2引起的PC12细胞损伤的神经保护作用研究

目的探讨布南色林对H_2O_2引起的大鼠嗜铬细胞瘤(PC12)细胞损伤的保护作用。方法取对数生长期PC12细胞,接种于96孔板,每孔加入终浓度为分别为0、5、10、20、40、80及160μmol·L^(-1)的布南色林,观察不同浓度布南色林对PC12细胞增殖的影响。另取细胞,分为空白细胞对照(C)组,H_2O_2处理(H)组,布南色林-H_2O_2处理(B)组,阳性对照(维生素E-H_2O_2处理,E)组)。MTT法检测各组细胞的活性变化。用TUNEL法检测各组细胞凋亡情况;倒置显微镜直接观察法以及Hoechst33258染色法观察氧化损伤细胞的形态变化;生化法测定各组细胞的超氧化物歧化酶(SOD)活性以及丙二醛(MDA)含量的改变。结果合适浓度的布南色林(0~20μmol·L^(-1))能促进PC12细胞的生长。与C组比较,H组的细胞活性下降,凋亡指数增加(P<0.05);细胞碎片增多,细胞损伤明显;细胞内的SOD活性减低,MDA水平增高(P<0.05)。与H组比较,B组的细胞活性增强,凋亡指数下降(P<0.05);细胞形态部分恢复;细胞内的SOD活性增强,MDA含量降低(P<0.05)。结论布南色林对H_2O_2引起的神经损伤有保护作用。

LC-MS/MS法测定人尿液中布南色林及其代谢物的浓度

目的建立测定人尿液中布南色林及其代谢产物N-去乙基布南色林(布南色林C)的药物质量浓度方法。方法尿液样品0.5 mL经饱和H2CO3水溶液0.2 mL碱化后用乙酸乙酯-二氯甲烷(体积比4∶1)萃取,布南色林与布南色林C分别以布南色林B和布南色林D为内标,采用LC-MS/MS法测定。色谱柱为Agilent Eclipse plus C18(4.6 mm×150 mm,3.5μm),以乙腈-水(体积比87∶13,含0.005 mol.L-1甲酸铵和质量分数0.1%甲酸)为流动相,流速为0.5 mL.min-1,柱温为40℃;质谱条件采用ESI离子源,检测方式为正离子电离,选择性离子监测(SRM),用于定量分析的离子反应分别为m/z 368.2→297.2(布南色林),m/z 396.3→297.2(布南色林B),m/z 340.2→297.1(布南色林C),m/z 356.2→313.3(布南色林D)。结果布南色林和布南色林C在10～2 000 ng.L-1(r2=0.997)范围内线性良好,其平均回收率分别为93.54%和74.50%以上,日内、日间精密度RSD值分别小于8.6%与16.4%。结论本试验建立的布南色林及布南色林C尿药质量浓度的测定方法简便、快速、准确、灵敏,可用于临床研究中布南色林及其代谢物的药动学研究与治疗药物监测。

顶空气相色谱法测定布南色林残留溶剂的含量

摘要：目的建立气相色谱法测定布南色林中残留溶剂含量的方法。方法采用6％氰丙基苯基-94％二甲基聚硅氧烷为固定液的毛细管柱（DB-624，0．53mm×30m，3．0μm），程序升温，初始温度50℃，保持5min，以20℃／min的速率升温至200℃，保持5min；氢火焰离子化检测器（FID），检测器温度250℃，进样口温度220℃，载气为氮气，流速2mL／min，进样体积1mL。外标法计算残留溶剂的含量。结果5种有机溶剂进样浓度与峰面积呈良好线性关系，相关系数均大于0．9990，加样回收率在97．6％～102．9％之间。结论此法准确可靠，灵敏度高，可用于布南色林中残留溶剂的测定。

电感耦合等离子体质谱法同时测定布南色林原料药中12种金属元素含量

目的建立同时测定布南色林原料药中12种金属元素含量的电感耦合等离子体质谱(ICP-MS)法。方法以硝酸为消解体系,采用微波消解法处理样品,以^(103)Rh和^(187)Re为内标,等离子体流量为18 L/min,雾化气流速为0.94 L/min,辅助气流量为1.2 L/min,射频功率为1.6 kW,模拟电压为-1635 V,脉冲电压为800 V。结果锂(Li)、铬(Cr)、钴(Co)、镍(Ni)、铜(Cu)、银(Ag)、镉(Cd)、钡(Ba)、铅(Pb)、铈(Ce)、钬(Ho)、镥(Lu)质量浓度均在0.5~80 ng/mL范围内与仪器响应值/内标测定值线性关系良好(r≥0.9996);检测限为0.001~0.147 ng/mL;精密度、稳定性、重复性试验结果的RSD均小于3.5%;平均回收率为91.29%~94.59%,RSD为1.93%~2.79%(n=9);3批样品中均仅检出Ni和Cu,平均含量分别为22.64 ng/g和12.10 ng/g。结论该方法操作简单,分析快速,测定结果准确,适用于同时测定布南色林原料药中多种金属元素的含量。

布南色林通过激活PI3K/AKT/GSK3β信号通路对精神分裂症大鼠海马神经元损伤的影响

目的探究布南色林对MK-801诱导精神分裂症大鼠海马神经元损伤及PI3K/AKT/GSK3β信号通路的影响。方法采用MK-801诱导精神分裂症模型,将48只SD大鼠随机分为正常组、模型组、布南色林组(1 mg/kg布南色林)、利培酮组(0.54 mg/kg利培酮)。通过刻板行为、旷场实验和Morris水迷宫实验观察大鼠行为学,用HE染色观察大鼠海马组织病理损伤并评分,检测血清糖脂代谢指标水平,实时荧光定量PCR和免疫印迹法检测海马组织磷脂酰肌醇3激酶(PI3K)、蛋白激酶B(AKT)、糖原合成酶激酶3β(GSK3β)mRNA和蛋白表达。结果与模型组比较,布南色林组和利培酮组刻板行为评分、旷场实验总路程、逃避潜伏期及海马组织病理损伤评分降低;穿越平台原位置次数,PI3K、AKT、GSK3βmRNA,PI3K、AKT和GSK3β磷酸化水平升高(P<0.05);但布南色林组和利培酮组上述指标的比较,差异无统计学意义。正常组、模型组和布南色林组空腹血糖(FPG)、糖化血红蛋白(HbA1c)、三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白(HDL)及低密度脂蛋白(LDL)水平的比较,差异无统计学意义,但利培酮组FPG、HbA1c、TG及TC水平较其他三组升高(P<0.05),HDL和LDL水平差异无统计学意义。结论布南色林可能通过激活PI3K/AKT/GSK3β信号通路对精神分裂症大鼠海马神经元损伤发挥神经保护作用,改善其认知功能和学习记忆能力。