盐酸吗茚酮(Molindone hydrochloride) - 药物靶点：D2 receptor_在研适应症：精神分裂症_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Molindone、Molindone XR、Molindone hydrochloride (USP)

+ [7]

靶点

D2 receptor

作用方式

拮抗剂

作用机制

D2 receptor拮抗剂(多巴胺D2受体拮抗剂)

治疗领域

神经系统疾病

在研适应症

精神分裂症

非在研适应症

攻击注意缺陷障碍伴多动品行障碍

原研机构

Strides Pharma Global Pte Ltd.

在研机构

Epic Pharma LLC

非在研机构

Supernus Pharmaceuticals, Inc.CHARTWELL RX SCIENCES LLC

最高研发阶段批准上市

首次获批日期

美国 (1974-01-18),

精神分裂症

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C16H24N2O2

InChIKeyKLPWJLBORRMFGK-UHFFFAOYSA-N

CAS号7416-34-4

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关联

10

项与盐酸吗茚酮相关的临床试验

NCT03638466

/ Terminated临床2期

Exploratory Neuroimaging Study to Evaluate the Effect on Brain Activity of SPN-810 for Impulsive Aggression (IA) in Patients With Attention-Deficit/Hyperactivity Disorder (ADHD) in Conjunction With Standard ADHD Treatment

The purpose of this study is to evaluate the effect of 4-week SPN-810 treatment on brain functioning in patients aged 8-12 years with ADHD and associated feature of impulsive aggression (IA). This will be achieved using functional magnetic resonance imaging (fMRI) in conjunction with the point subtraction aggression paradigm (PSAP) Task, a behavioral aggression paradigm in which subjects are provoked by having money indirectly taken from them by a fictitious opponent, simulating an aggression response.

开始日期2019-05-30

申办/合作机构

Supernus Pharmaceuticals, Inc.

NCT03597503

/ Terminated临床3期

Assessment of Efficacy and Safety of SPN-810 for the Treatment of Impulsive Aggression (IA) in Adolescent Subjects With Attention Deficit/Hyperactivity Disorder (ADHD) in Conjunction With Standard ADHD Treatment

The purpose of this study was to evaluate the effect of SPN-810 for the treatment of impulsive aggression (IA) in adolescents diagnosed with ADHD when taken in conjunction with standard ADHD treatment.

开始日期2018-07-31

申办/合作机构

Supernus Pharmaceuticals, Inc.

NCT02691182

/ Terminated临床3期

Open-Label Extension Study to Evaluate the Long-Term Safety of Molindone Hydrochloride Extended-Release Tablets for the Treatment of Impulsive Aggression in Pediatric and Adolescent Subjects With Attention Deficit/Hyperactivity Disorder (ADHD) in Conjunction With Standard ADHD Treatment

Children between the ages of 6-12 years who are diagnosed with impulsive aggression comorbid with ADHD and have participated in the 810P301 or 810P302 study were invited to participate in this study. This was a Phase 3 open-label extension (OLE) study to collect long-term safety data on the use of SPN-810 in treating impulsive aggression in pediatric subjects with ADHD when taken in conjunction with standard ADHD treatment. After confirmation of eligibility, all subjects were treated with SPN-810. Subjects were given a choice to extend participation in this study every 6 months for up to 36 months.

开始日期2016-04-01

申办/合作机构

Supernus Pharmaceuticals, Inc.

100 项与盐酸吗茚酮相关的临床结果

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100 项与盐酸吗茚酮相关的转化医学

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100 项与盐酸吗茚酮相关的专利（医药）

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412

项与盐酸吗茚酮相关的文献（医药）

2024-12-01·Science of The Total Environment

Temporal trends and sources of organic micropollutants in wastewater

Article

作者: Christensen, Jan H ; Mortensen, Peter ; Jørgensen, Mathias B ; Tisler, Selina ; Kilpinen, Kristoffer

Effluent wastewater from conventional wastewater treatment plants (WWTPs) is a source of environmental micropollutants. This study investigated temporal trends of organic micropollutants in effluent wastewater, aiming to identify underlying drivers and their implications for treatment efficiency. From September to December 2022, we collected 168 effluent and 10 influent samples. These samples were concentrated using a three-layer solid-phase extraction method and analyzed by liquid chromatography-high resolution mass spectrometry (LC-HRMS). Both targeted and suspect screening approaches were employed, allowing for the full quantification of 64 micropollutants and the identification of 90 additional compounds through suspect screening. Correlations revealed distinct groups of micropollutants with similar temporal trends, indicating common sources or behaviors during treatment. Notably, caffeine and paracetamol showed strong correlations with influent flow rates, indicating their removal efficiency is significantly influenced by hydraulic conditions. PFAS compounds, tire-wear chemicals, and biocides correlated with rain events. Micropollutants were categorized into nine groups based on their temporal trends, linking them to sources and persistence in the WWTP. Industrial discharges significantly contributed to spikes in pharmaceuticals like amitriptyline and citalopram. Metabolite analysis effectively distinguishing between sources of consumption and industrial discharge. These findings underscore the need for regulatory frameworks addressing a broader range of micropollutants. Key events such as rain and industrial discharges impact micropollutant composition and concentrations in effluent wastewater. Our study provides insights into their dynamics within WWTPs, informing improved treatment strategies.

2024-09-01·British Journal of Clinical Pharmacology

Assessing the anticholinergic cognitive burden classification of putative anticholinergic drugs using drug properties

Article

作者: Phutietsile, Geofrey Oteng ; Fotaki, Nikoletta ; Nishtala, Prasad S.

AimsThis study evaluated the use of machine learning to leverage drug absorption, distribution, metabolism and excretion (ADME) data together with physicochemical and pharmacological data to develop a novel anticholinergic burden scale and compare its performance to previously published scales.MethodsExperimental and in silico ADME, physicochemical and pharmacological data were collected for antimuscarinic activity, blood–brain barrier penetration, bioavailability, chemical structure and P‐glycoprotein (P‐gp) substrate profile. These five drug properties were used to train an unsupervised model to assign anticholinergic burden scores to drugs. The model performance was evaluated through 10‐fold cross‐validation and compared with the clinical Anticholinergic Cognitive Burden (ACB) scale and nonclinical Anticholinergic Toxicity Scores (ATS) scale, which is based primarily on muscarinic binding affinity.ResultsIn silico software (ADMET Predictor) used for screening drugs for their blood–brain barrier (BBB) penetration correctly identified some drugs that do not cross the BBB. The mean area under the curve for the unsupervised and ACB scale based on the five selected variables was 0.76 and 0.64, respectively. The unsupervised model agreed with the ACB scale on the classification of more than half of the drugs (49 of 88) agreed on the classification of less than half the drugs in the ATS scale (12 of 25).ConclusionsOur findings suggest that the commonly used ACB scale may misclassify certain drugs due to their inability to cross the BBB. By contrast, the ATS scale would misclassify drugs solely depending on muscarinic binding affinity without considering other drug properties. Machine learning models can be trained on these features to build classification models that are easy to update and have greater generalizability.

2024-09-01·Psychiatry Research

Dopamine D2 receptor antagonism of antipsychotics and the risk of death due to choking

Article

作者: Luykx, Jurjen J ; Manu, Peter ; Taipale, Heidi ; Hasan, Alkomiet ; Correll, Christoph U ; Lähteenvuo, Markku ; Tiihonen, Jari ; Tanskanen, Antti ; Lieslehto, Johannes

The risk of fatal choking for people with schizophrenia and associations with antipsychotic medication are largely unknown. Therefore, we calculated the choking-related standardized mortality ratio for schizophrenia relative to the general population (SMR_choking). We also computed adjusted hazard ratios (aHR) of choking-related mortality for antipsychotics in a nationwide cohort of patients with schizophrenia (N = 59,916). SMR_choking was 20.5 (95 % confidence interval (CI)=17.1-23.9). The aHR was 1.74 (95 %CI=1.19-2.55) for strong dopamine 2-antagonists. For other antipsychotics, CIs included 1. Importantly, aHRs were particularly high for high dose categories of strong dopamine D2 receptor (D2R) antagonists. In conclusion, a schizophrenia diagnosis is associated with a 20-fold risk of death due to choking. This risk is elevated during use of strong D2R antagonist antipsychotics, particularly when prescribed in high dosages.

1

项与盐酸吗茚酮相关的新闻（医药）

2024-10-25

·奇点网

改善认知看来不是抗精神病药物的长项。

*仅供医学专业人士阅读参考认知功能缺陷是精神分裂症谱系障碍（SSDs）的重要症状之一，涵盖注意力、专注力、记忆等多个方面，对疾病进程和患者生活质量有着深远影响。作为SSDs患者的关键治疗手段，抗精神病药物虽然不是专门用于改善认知功能的药物，但由于其受体结合特性，被认为可能对认知功能产生不同程度的影响。然而结果有些差强人意。德国慕尼黑工业大学的Stefan Leucht团队完成了迄今为止最全面的关于抗精神病药物与精神分裂症谱系障碍（SSDs）患者认知功能关系的网络荟萃分析，结果于近日发表在《JAMA·精神病学》期刊上。他们基于包含近千名SSD患者的68项试验数据进行分析后发现，抗精神病药物整体上对认知功能有轻微的改善效果，略胜于安慰剂，但不具有统计学意义。每种药物之间的效果差异不大，其中氯氮平、氟哌啶醇、氟奋乃静在认知功能的改善方面表现垫底，逊色于安慰剂。研究者们表示，抗精神病药物对认知功能的轻微改善可能更多是由于其减少了思维紊乱和其它阳性症状（比如激动、妄想、幻觉等），而非直接作用于认知功能本身。论文首页截图在这项研究中，Stefan Leucht等人通过系统回顾和随机效应网络荟萃分析，评估了抗精神病药物对精神分裂症谱系障碍（SSDs）患者认知功能的影响。研究的主要数据来源于Cochrane精神分裂症组试验注册库，截至2023年6月25日，共筛选并纳入68项随机对照试验，涉及9525名SSDs患者。这些患者的平均年龄为35.1岁，男性占70%。研究的主要结局是患者整体认知功能的变化，次要结局是患者具体认知领域（如处理速度、工作记忆、语言学习等）、生活质量和社会功能的变化。结果显示，整体上，抗精神病药物对认知功能的改善效果有限，虽然相比安慰剂表现出一定的优势，但效应值（SMD）较小，并且不同药物之间的差异不明显。具体来说，在改善认知的效果上，吗茚酮（Molindone，MOL）和盐酸硫利达嗪（Thioridazine，THIOR）分别排名第一和第二。不过这两种药物的分析结果都是基于单项小规模研究（15-22人数），且仅改善大脑处理速度这一个认知领域。同样，位列第五的氯丙嗪（Chlorpromazine，CPZ）也存在这个问题，但尽管相关研究数量多了些，总参与人数依然较少（N=101），且数据来源于二十世纪六七十年代的随机临床试验。相比之下，位列第三、第四的帕利哌酮（Paliperidone，PAL）和舍吲哚（Sertindole，SER），其分析结果基于近年来的研究数据，与安慰剂相比，表现出中等效果（SMD -0.43，95%CI -0.93至0.08 ；SMD -0.57，95%CI -1.03至 -0.11）。排名倒数的三位，则是氟奋乃静（Fluphenazine，FLU）（SMD = 0.15, 95% CI = -0.39至0.69）、氟哌啶醇（Haloperidol，HAL）（SMD 0.04，95%CI -0.25至0.33）、氯氮平（Clozapine，CLZ）（SMD 0.12，95%CI -0.23至0.48），落后于安慰剂。这一结果与它们的强效多巴胺型受体阻断作用相符。其他排名靠前的药物还有喹硫平（Quetiapine，QUE）、布瑞吡唑（Brexpiprazole，BRE）、利培酮（Risperidone，RIS）、唑吡坦（Zotepine，ZOT）、奥氮平（Olanzapine，OLA）、氨磺必利（Amisulpride，AMI）、鲁拉西酮（Lurasidone，LUR）、阿立哌唑（Aripiprazole，ARI）、齐拉西酮（Ziprasidone，ZIP）。排名（PLB-安慰剂）在额外的探索性事后分析中，研究按照抗精神病药物的结合受体将其分为四个组。结果显示，作用于肾上腺素能受体、5-羟色胺能药物、毒蕈碱型受体、多巴胺受体的四组药物，相比于安慰剂对患者认知功能都有改善的趋势。按作用受体分类时，每组抗精神病药物都有点小优但不明显某些药物在个别领域表现出较为积极的效果，比如刚才提到的吗茚酮和盐酸硫利达嗪对于SSD患者大脑处理速度的提高。相比于安慰剂，布瑞吡唑在视觉学习方面显示出小幅但显著的积极效果，帕利哌酮在语言学习和工作记忆方面有改善的趋势。研究还评估了患者的生活质量和社会功能，然而整体来看抗精神病药物在这些方面的表现同样有限，未能显著优于安慰剂，而且纳入分析的各项研究中认知评估工具所提供的证据也不明确。药物对具体认知功能的改善效果过去相关的荟萃分析和网络荟萃分析存在时效性不足、新药物的纳入有限、方法学质量较低等限制，并缺乏对抗精神病药物与安慰剂的直接比较。这项研究迄今为止最大的相关领域研究，表明尽管某些药物显示出小幅认知改善，但大多数抗精神病药物的效应较小，且部分药物的结果因样本小而不具备足够的意义，很难区分这些改善是否源于减少思维紊乱等症状。这些结果为临床实践中抗精神病药物的选择提供了有价值的最新见解，同时也强调了统一认知评估标准的重要性，以便未来研究能够更有效地比较不同药物的效果。另外，研究者们呼吁开发新的抗精神病药物，特别是那些针对认知缺陷的新型机制药物，以更好地满足SSDs患者的治疗需求。参考文献：[1]https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2825154本文作者丨张艾迪

临床研究

100 项与盐酸吗茚酮相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00796	盐酸吗茚酮	N05AE02	DB01618

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
精神分裂症	美国	Epic Pharma LLC	2015-03-20

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
攻击	临床2期	美国	Supernus Pharmaceuticals, Inc.	2018-07-31
注意缺陷障碍伴多动	临床2期	美国	Supernus Pharmaceuticals, Inc.	2016-01-25
注意缺陷障碍伴多动	药物发现	美国	Supernus Pharmaceuticals, Inc.	2016-01-25
品行障碍	药物发现	美国	Supernus Pharmaceuticals, Inc.	2008-09-01

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02691182 (CTgov)	临床3期	注意缺陷障碍伴多动	491	SPN-810 (<18 mg SPN-810)	艱淵淵膚壓鹹顧壓糧糧(夢憲齋範鑰窪獵繭廠餘) = 餘醖網鬱醖膚製繭醖膚鹹艱鹹繭獵壓顧窪觸顧 (壓廠鹹網餘壓艱蓋餘選, 淵築糧齋選簾鬱餘選壓 ~ 鹽鏇膚願夢糧願範醖簾) 更多	-	2024-05-16
				SPN-810 (18 mg to < 24 mg SPN-810)	艱淵淵膚壓鹹顧壓糧糧(夢憲齋範鑰窪獵繭廠餘) = 窪簾廠齋網壓觸淵夢醖鹹艱鹹繭獵壓顧窪觸顧 (壓廠鹹網餘壓艱蓋餘選, 蓋襯鑰顧築繭構鏇廠壓 ~ 窪糧淵製鑰網襯淵膚醖) 更多
NCT02618434 (CTgov)	临床3期	注意缺陷障碍伴多动	297	Placebo (Placebo)	窪網繭願願醖構獵選窪(鹹夢簾醖齋夢憲憲願願) = 範醖繭製鏇鬱鹹簾鑰顧膚蓋繭積鏇夢鏇製顧構 (糧觸齋膚襯顧襯築繭簾, 窪窪蓋製選醖鑰廠窪鏇 ~ 壓簾簾簾選鹹鑰憲壓觸) 更多	-	2024-03-18
				SPN-810 (36 mg) (High Dose SPN-810 (36 mg))	窪網繭願願醖構獵選窪(鹹夢簾醖齋夢憲憲願願) = 廠鹹選鑰淵網襯鬱範鹽膚蓋繭積鏇夢鏇製顧構 (糧觸齋膚襯顧襯築繭簾, 鬱願壓構壓廠艱鏇蓋鬱 ~ 膚夢窪網簾廠範簾廠築) 更多
NCT03597503 (CTgov)	临床3期	攻击 \| 注意缺陷障碍伴多动	41	Placebo (Placebo)	繭鏇淵鹹網夢構選醖構(襯鏇鏇窪衊夢艱顧積艱) = 觸網獵窪積鏇膚夢製鑰鹽觸廠鏇鏇淵顧網範鹹 (蓋鏇蓋鏇鑰鹹壓鹽觸範, 繭簾鏇獵繭壓淵觸淵餘 ~ 製廠衊餘鏇憲窪窪艱壓) 更多	-	2024-02-20
				SPN-810 (Flexible Dose of SPN-810)	繭鏇淵鹹網夢構選醖構(襯鏇鏇窪衊夢艱顧積艱) = 廠築選積襯築衊顧憲簾鹽觸廠鏇鏇淵顧網範鹹 (蓋鏇蓋鏇鑰鹹壓鹽觸範, 選鹽鏇製網繭糧選衊獵 ~ 顧製網築鏇蓋醖壓製憲) 更多
NCT02618408 (CTgov)	临床3期	注意缺陷障碍伴多动	333	Placebo (Placebo)	鑰獵壓鑰齋衊遞鏇簾築(網窪鑰選淵糧糧繭淵觸) = 窪鹽築觸蓋艱襯壓齋廠繭艱範顧製蓋鬱遞憲網 (鏇糧積選壓構憲積膚齋, 壓積鬱蓋範襯膚築鏇顧 ~ 餘築蓋醖繭淵衊鹹鑰鹽) 更多	-	2022-11-01
				SPN-810 (18 mg) (Low Dose SPN-810 (18 mg))	鑰獵壓鑰齋衊遞鏇簾築(網窪鑰選淵糧糧繭淵觸) = 淵鹹餘簾鹽構襯鹹廠艱繭艱範顧製蓋鬱遞憲網 (鏇糧積選壓構憲積膚齋, 壓選膚鹽齋簾壓壓醖膚 ~ 鏇鏇簾廠簾網遞醖淵衊) 更多
NCT00053703 (TEOSS, CTgov)	临床4期	精神分裂症	116	Olanzapine (enrollment closed in this treatment) (Olanzapine)	襯製願憲憲艱簾築憲鹹(積築艱範壓製製鑰網膚) = 夢壓齋夢網築積鏇鏇窪獵鹽網網獵淵憲願齋鹽 (遞齋蓋構窪壓獵願襯顧, 構鏇餘觸選鬱膚製積齋 ~ 簾夢積蓋顧夢構餘鏇鑰) 更多	-	2014-03-26
				risperidone (Risperidone)	襯製願憲憲艱簾築憲鹹(積築艱範壓製製鑰網膚) = 獵築艱顧顧願膚艱淵夢獵鹽網網獵淵憲願齋鹽 (遞齋蓋構窪壓獵願襯顧, 夢構鹽鑰遞壓顧鑰壓艱 ~ 願壓範鏇簾衊壓範簾醖) 更多