An Open-Label, Randomized, Two-Treatment, Two-Period, Two-Sequence, Multiple-Dose, Steady-State, Fully Replicate, Crossover Bioequivalence Study of Aripiprazole 400 mg Powder and Solvent for Prolonged-Release Suspension for Injection and Abilify Maintena® 400 mg Powder and Solvent for Prolonged-Release Suspension for Injection in Adult Patients withSchizophrenia under Fasting Condition. - NIL

开始日期2024-12-02

申办/合作机构

Laboratorios Liconsa SA

[+1]

TCTR20240524006 / Not yet recruiting临床1期IIT

A randomized, open-label, single dose, two-way crossover design with two-period, two-treatment and two-sequence bioequivalence study of Aripiprazole Tablets 10 mg relative to Abilify (Aripiprazole Tablets 10 mg) in healthy Thai volunteers under fasting condition.

开始日期2024-11-13

申办/合作机构

Bio-innova Co., Ltd

NCT06580041 / Enrolling by invitation临床4期IIT

Precision Care for Major Depressive Disorder

This study aims to assess whether phenotyping-guided intervention selection is superior to intervention selection without phenotyping guidance (i.e., routine clinician and patient judgment regarding treatment selection) for depression.

开始日期2024-11-12

申办/合作机构

The University of California, San Francisco

100 项与 D3 receptor 相关的临床结果

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100 项与 D3 receptor 相关的转化医学

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0 项与 D3 receptor 相关的专利（医药）

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2,867

项与 D3 receptor 相关的文献（医药）

2025-04-01·Neural Regeneration Research

Cortico-striatal gamma oscillations are modulated by dopamine D3 receptors in dyskinetic rats

Article

作者: Zhang, Wangming ; Chen, Jiazhi ; Wang, Pengfei ; Zhou, Ming ; Wen, Huantao ; Wang, Zhuyong ; Luo, Minjie ; Bi, Yuewei ; Li, Min

JOURNAL/nrgr/04.03/01300535-202504000-00031/figure1/v/2024-07-06T104127Z/r/image-tiff Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia. Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia. Currently, studies have reported increased oscillation power in cases of levodopa-induced dyskinesia. However, little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia. Furthermore, the role of the dopamine D3 receptor, which is implicated in levodopa-induced dyskinesia, in movement disorder-related changes in neural oscillations is unclear. We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease. Furthermore, levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components, as well as bidirectional primary motor cortex (M1) ↔ dorsolateral striatum gamma flow. Administration of PD128907 (a selective dopamine D3 receptor agonist) induced dyskinesia and excessive gamma oscillations with a bidirectional M1 ↔ dorsolateral striatum flow. However, administration of PG01037 (a selective dopamine D3 receptor antagonist) attenuated dyskinesia, suppressed gamma oscillations and cortical gamma aperiodic components, and decreased gamma causality in the M1 → dorsolateral striatum direction. These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity, and that it has potential as a therapeutic target for levodopa-induced dyskinesia.

2024-12-01·Carbohydrate Polymers

Antibody conjugated targeted nanotherapy epigenetically inhibits calpain-mediated mitochondrial dysfunction to attenuate Parkinson’s disease

Article

作者: Sardoiwala, Mohammed Nadim ; Sahu, Vikas Kumar ; Biswal, Liku ; Karmakar, Surajit ; Choudhury, Subhasree Roy

Many neurodegenerative and psychiatric malignancies like Parkinson' disease (PD) originate from an imbalance of 17β-Estradiol (E2) in the human brain. However, the peripheral side effects of the usage of E2 for PD therapy and less understanding of the molecular mechanism hinder establishing its neurotherapeutic potential. In the present work, systemic side effects were overcome by targeted delivery using Dopamine receptor D3 (DRD3) conjugated E2-loaded chitosan nanoparticles (Ab-ECSnps) that showed a promising delivery to the brain. E2 is a specific calpain inhibitor that fosters neurodegeneration by disrupting mitochondrial function, while B-cell-specific Moloney murine leukemia virus integration region 1 (BMI1), an epigenetic regulator, is crucial in preserving mitochondrial homeostasis. We showed the administration of Ab-ECSnps inhibits calpain's translocation into mitochondria while promoting the translocation of BMI1 to mitochondria, thereby conferring neurotherapeutic benefits by enhancing cell viability, increasing mitochondrial DNA copy number, and preserving mitochondrial membrane potential. Further, we showed a novel molecular mechanism of BMI1 regulation by calpain that might contribute to maintaining mitochondrial homeostasis for attenuating PD. Concomitantly, Ab-ECSnps showed neurotherapeutic potential in the in vivo PD model. We showed for the first time that our brain-specific targeted delivery might regulate calpain-mediated BMI1 expression, thereby preserving mitochondrial homeostasis to alleviate PD.

2024-11-01·International Journal of Obesity

Novel genomic variants related to visceral adiposity index (VAI) and body adiposity index (BAI) in Indian sib-pairs

Article

作者: Chandak, Giriraj Ratan ; Khadgawat, Rajesh ; Smith, George Davey ; Agarwal, Tripti ; Relton, Caroline ; Gupta, Vipin ; Dudbridge, Frank ; Lyngdoh, Tanica ; Walia, Gagandeep Kaur ; Ebrahim, Shah ; Kinra, Sanjay ; Prabhakaran, Dorairaj

BACKGROUNDObesity is among the leading public health threats globally. Over the last few years, visceral adiposity index (VAI), and body adiposity index (BAI), derived from anthropometric, and biochemical measures, have gained importance as a measure of obesity. However, unlike other common indices like body mass index, and waist circumference, the genetic predisposition of VAI, and BAI under-examined.METHODS2265 sib-pairs from Indian Migration Study were used for examining the association of genetic variants from the Cardio-Metabochip array with VAI, and BAI. Mixed linear regression models were run, and all inferences were based on the within-sib component of the Fulker's association models. Gene-environment/lifestyle interaction analyses were also undertaken.RESULTSrs6659428 at LOC400796 | SEC16B (β = 0.26, SE = 0.05), and rs7611535 at DRD3 | LOC645180 (β = 0.18, SE = 0.04) were associated with VAI at suggestive significance value of <8.21 × 10^-6. For BAI, rs73300702 at JAZF1-AS1 (β = 0.27, SE = 0.06), was the top hit at p value < 8.21 × 10^-6. Further, rs6659428 showed marginal effect modification with rural/urban location (β = 0.26, SE = 0.13, p value = 0.047), and rs73300702 with physical activity (β = -0.29,SE = 0.14, p value = 0.034).CONCLUSIONWe report three novel genetic loci for VAI, and BAI in Indians that are important indicators of adiposity. These findings need to be replicated and validated with larger samples from different ethnicities. Further, functional studies for understanding the biological mechanisms of these adiposity indices need to be undertaken to understand the underlying pathophysiology.

项与 D3 receptor 相关的新闻（医药）

2024-10-10

·医药观澜

针对精神分裂症，超15款在研新药正在中国开展临床研究丨世界精神卫生日

▎药明康德内容团队报道今日（10月10日）是世界精神卫生日。精神分裂症作为一种常见的严重精神疾病，再次引起广泛的关注。根据世界卫生组织（WHO）数据[1]，全球范围内约有2400万人正遭受着精神分裂症的折磨，即每300人中就有1人患有精神分裂症（0.32%）。尽管当下一些疗法可以有效控制某些症状，但仍有很大一部分患者对现有疗法无效，或出现不可接受的副作用。精神分裂症新药开发难度大，失败率高，研发界一直期待能够在这一领域有新的突破。好消息是，随着科学研究的进展，这一领域已经迎来了诸多有希望的进展。本文将根据公开资料，整理当前在中国正在研发的部分精神分裂症产品管线，仅供读者参阅。（注：本文为不完全统计，仅盘点部分在中国正在开展临床研究的精神分裂症在研管线。）图片来源：123RF 再鼎医药/百时美施贵宝：KarXT 作用机制：M1/M4毒蕈碱乙酰胆碱受体激动剂中国研发阶段：3期临床 KarXT（xanomeline-trospium）是一种毒蕈碱类抗精神病药物。该产品于今年9月27日获美国FDA批准，用于治疗成人精神分裂症。彼时FDA新闻稿指出，这是靶向胆碱能受体的首个抗精神病药物，也标志着数十年来首个治疗精神分裂症的新机制药物。KarXT在中枢神经系统中充当M1/M4毒蕈碱乙酰胆碱受体激动剂，被认为可以改善精神分裂症的阳性、阴性和认知症状。且与现有疗法不同，KarXT不会直接阻断多巴胺受体。在中国，再鼎医药拥有KarXT在大中华区的权益。再鼎医药正在开展一项评估KarXT用于精神分裂症的3期桥接注册研究。勃林格殷格翰：lclepertin（BI 425809）作用机制：Gly-T1抑制剂中国研发阶段：3期临床 Iclepertin是勃林格殷格翰（Boehringer Ingelheim）管线中一款新型甘氨酸转运蛋白1（Gly-T1）抑制剂，通过抑制Gly-T1，改善N-甲基-D-天冬氨酸（NMDA）受体的功能减退起到治疗作用。NMDA受体功能低下导致的谷氨酸能途径异常是精神分裂症发病的病理原因之一。目前该产品正在开展针对精神分裂症的全球3期临床，中国同步参与其中。2021年5月，FDA 基于一项2期临床试验的积极结果，授予lclepertin治疗精神分裂症的突破性疗法认定。同年6月，该产品在中国被CDE纳入突破性治疗品种，用于治疗与精神分裂症相关的认知障碍（CIAS）。中泽医药：ZZ6398 作用机制：D2/D3/5-HT1A/5-HT2A受体泛拮抗剂中国研发阶段：2期临床 ZZ6398是一款D2、D3、5-HT1A和5-HT2A四个受体泛拮抗剂，可通过合理D2/D3选择性和5-HT1A拮抗作用，来同时改善精神分裂阳性、阴性和认知症状。目前，中泽医药正在开展该产品针对精神分裂症患者的一项1b/2a期临床研究。翰森制药：HS-10380片作用机制：多靶点激动剂中国研发阶段：2期临床 HS-10380是翰森制药神经系统疾病领域的研发项目之一，为一款D2、D3受体和5-HT1A部分受体多靶点激动剂，对5-HT2A受体具显著拮抗作用，有望改善精神疾病患者的症状。根据药物临床试验登记与信息公示平台，翰森制药正在开展HS-10380片治疗急性期精神分裂症的一项2期临床研究，以及一项针对中国成年精神分裂症患者的1b/2期临床研究。灵北制药/恩华药业：Lu AF35700/NHL35700 作用机制：小分子靶向药中国研发阶段：2期临床 Lu AF35700是灵北公司（Lundbeck）开发的一款口服小分子药物，拟治疗难治性精神分裂症。公开资料显示，该产品可靶向多巴胺受体、血清素受体和肾上腺素受体，对多巴胺D1受体的亲和力高于D2受体，其药理学机制有望减少锥体外系反应、高泌乳素血症等副作用的发生率。2021年11月，恩华药业与灵北达成合作，获得Lu AF35700在大中华区的独家权益。根据中国药物临床试验登记与信息公示平台，一项评价NHL35700治疗精神分裂症的2期临床试验正在进行中。京新药业：JX11502MA片作用机制：多巴胺D3/D2受体部分拮抗/激动剂中国研发阶段：2期临床公开资料显示，JX11502MA为京新药业在研的一款多巴胺D3/D2受体部分拮抗/激动剂，它同时对5-HT1A和5-HT2A受体具有拮抗作用，可以改善精神分裂症患者的情感淡漠。根据药物临床试验登记与信息公示平台，京新药业正在开展一项2b期和一项2c期临床研究，评估JX11502MA针对成人急性期精神分裂症的有效性和安全性。绿叶制药：LY03020 作用机制：TAAR1/5-HT2CR双靶点激动剂中国研发阶段：1期临床 LPM787000048马来酸盐缓释片（LY03020）为绿叶制药开发的一款痕量胺相关受体1（TAAR1）和5-羟色胺2C受体（5-HT2CR）双靶点激动剂。目前，该产品针对精神分裂症和阿尔茨海默病精神病性障碍的1期临床研究均已启动。据公开资料，不同于已上市抗精分药物抑制突触后膜D2和5-HT2A受体的机制，新一代抗精分药物以激动突触前膜为特征。TAAR1和5-HT2CR双靶点作用机制可起到提高疗效，减少不良反应的作用，有望减少锥体外系反应（EPS）和代谢综合征等不良反应，并可显著改善精神分裂症阴性症状和认知症状等。礼来/索元生物：DB103（pomaglumetad methionil）作用机制：强效mGlu2/3受体激动剂中国研发阶段：1期临床 DB103是索元生物从礼来公司（Eli Lilly and Company）引入的一款新药，是一种强效mGlu2/3受体 (mGlu2/3R)激动剂 (LY404039) 的甲硫氨酸前体药物，计划开发用于治疗精神分裂症。据索元生物官网介绍，LY404039的临床前特征显示了潜在的临床疗效，但在人体胃肠道中的生物利用度非常差。向LY404039添加氨基酸甲硫氨酸，可通过经由人肽转运蛋白（hPepT1）的主动转运作用，而提高口服生物利用度。根据中国药物临床试验登记与信息公示平台，一项DB103在早期精神分裂患者中的1b期研究已经完成。恩华药业：NH300231肠溶片作用机制：5-HT2A受体拮抗剂和多巴胺受体调节剂中国研发阶段：1期临床 NH300231是恩华药业研发的1类新药，为新一代非典型抗精神分裂症药物。它是一种5-HT2A受体拮抗剂和多巴胺受体调节剂，且对5-HT2A受体的拮抗活性明显高于多巴胺D2受体，同时能够抑制五羟色胺转运体活性。根据中国药物临床试验登记与信息公示平台官网，恩华药业正在开展一项1期临床研究，评估单次口服NH300231的安全性、耐受性和药代动力学特征。旺山旺水生物医药/中国科学院上海药物研究所：TPN672 作用机制：双向调节多巴胺受体中国研发阶段：1期临床 TPN672是一款在研抗精神分裂症药物，由中国科学院上海药物研究所和旺山旺水生物医药共同开发。公开信息显示，TPN672对多巴胺受体具有双向调节作用，并同时作用于5-羟色胺受体和5-羟色胺转运体，从而起到平衡调节中枢神经系统功能的作用。它在临床前研究中表现出改善精神分裂症阴性症状和认知功能的作用。根据中国药物临床试验登记与信息公示平台，该产品已经完成两项1期临床，还有一项评价TPN672片在精神分裂症患者的1b期临床研究目前状态为主动暂停。默沙东（MSD）：MK-8189 作用机制：PDE10A选择性抑制剂中国研发阶段：1期临床 MK-8189是一款磷酸二酯酶10A（PDE10A）的选择性抑制剂。PDE10A在人脑纹状体中大量表达，而在其他组织中没有。纹状体的异常输出与精神分裂症阳性症状有关，包括精神病、幻觉和妄想。临床前研究表明，PDE10A抑制剂有可能缓解多巴胺能和谷氨酸能功能障碍，表明MK-8189除了精神病症状外，还可能对认知障碍具广谱活性。MK-8189已在精神分裂症患者中完成多项1期试验，在全球正在进行2期临床。根据中国药物临床试验登记与信息公示平台，一项评价MK-8189在健康中国受试者中的安全性、耐受性和药代动力学行为的多次给药临床研究已经完成。旺山旺水生物：VV119胶囊中国研发阶段：1期 VV119胶囊为一款化药1类新药，于2023年在中国获批IND。根据中国药物临床试验登记与信息公示平台官网，旺山旺水生物正在开展两项1期临床研究，分别评估单次和多次口服VV119胶囊，在中国成年健康受试者和精神分裂症患者中的安全性、耐受性和药代动力学特征。翰森制药：HS-10509片中国研发阶段：1期 HS-10509片为翰森制药在研的一款1类化药新药，目前正在开展针对中国精神分裂症成人患者的1期临床研究。绿叶制药：LPM526000133富马酸盐胶囊（LY03017）中国研发阶段：1期绿叶嘉奥制药申报的LPM526000133富马酸盐胶囊已在中国获批临床，拟开发治疗精神分裂症阴性症状（NSS）、帕金森病精神病性障碍（PDP）相关的幻觉和妄想、阿尔茨海默病精神病性障碍（ADP）相关的幻觉和妄想。根据中国药物临床试验登记与信息公示平台，绿叶制药已针对该产品开展三项1期临床研究，评估其安全性、耐受性和药代动力学。恩华药业：CY150112 中国研发阶段：1期临床 CY150112片是恩华药业正在研发的一款小分子药物（尚未披露靶点机制），于2020年在中国获批临床，开展精神分裂症的临床试验。根据中国药物临床试验登记与信息公示平台，一项评价CY150112片在成人健康受试者中滴定给药及多次给药的1b期临床研究正在招募中。纽欧申医药：NS-136 作用机制：毒蕈碱型乙酰胆碱M4受体正向变构调节剂中国研发阶段：获批临床 NS-136片是纽欧申医药研发的一款新型选择性毒蕈碱型乙酰胆碱M4受体正向变构调节剂（M4 PAM）。纽欧申医药此前新闻稿介绍，对M4受体进行正向调节是治疗精神分裂症的新作用机制，尤其是对阴性症状和认知功能损伤的改善被认为是精神分裂症治疗重要的进步。NS-136片此前已在澳大利亚启动1期临床研究。今年7月，该产品在中国获批IND，适应症为精神分裂症。参考资料： [1]各公司官网及公开新闻稿 [2]中国药物临床试验登记与信息公示平台官网. From http://www.chinadrugtrials.org.cn/index.html [3]WHO官网. From https://www-who-int.libproxy1.nus.edu.sg/news-room/fact-sheets/detail/schizophrenia 本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权及其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

突破性疗法临床2期临床3期临床1期

2024-09-18

·GlobeNewswire-Health Care

Engrail Therapeutics Initiates ENX-104 Clinical Program for the Treatment of Major Depressive Disorder Characterized by Anhedonia

The first-in-human Phase 1 clinical study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic profile of ENX-104 in healthy volunteers SAN DIEGO, Sept. 18, 2024 (GLOBE NEWSWIRE) -- Engrail Therapeutics, a precision neuroscience company focused on the development of transformational therapies to improve the lives of patients, today announced initiation of a Phase 1 single ascending dose clinical study for ENX-104 in healthy volunteers. ENX-104 is a potent and selective dopamine D2/D3 receptor antagonist designed to enhance dopamine neurotransmission by preferential autoreceptor inhibition at low doses. The lead indication for ENX-104 is the treatment of major depressive disorder (MDD) characterized by anhedonia (aMDD). Anhedonia is the inability to experience pleasure in normally pleasurable activities and is a core symptom of MDD that is largely unresponsive to currently approved antidepressants. “Dysregulation of dopamine in the reward centers of the brain is believed to underlie anhedonia which is experienced by 60-70% of MDD patients. ENX-104 provides a novel and targeted approach to enhancing dopamine modulation and represents a potential new therapeutic modality for the treatment of patients with aMDD,” said Vikram Sudarsan, PhD, chief executive officer of Engrail. “The initiation of this Phase 1 study is a significant step forward for ENX-104 and an important milestone for Engrail as our second clinical-stage program.” The ENX-104 Phase 1 study is a randomized, double-blind, placebo-controlled single ascending dose clinical study that is expected to enroll up to 48 healthy adult volunteers. The primary objective is to evaluate the safety and tolerability of ENX-104 after a single oral administration of increasing doses in separate cohorts. Each dose cohort will include 8 subjects, with 6 subjects randomized to ENX-104 and 2 to placebo. The study is also designed to measure pharmacokinetics and explore the pharmacodynamic effects of ENX-104 on biomarkers associated with changes in dopamine neurotransmission in order to ascertain target engagement. About ENX-104ENX-104 is a potent dopamine D2/D3 receptor antagonist in development for major depressive disorder (MDD) characterized by anhedonia (aMDD). Dysregulated dopaminergic neurotransmission, particularly in brain reward systems, is believed to underlie anhedonia, a hallmark symptom of MDD. ENX-104 was designed to directly modulate dopaminergic transmission in brain reward systems by increasing dopamine release via potent antagonism of presynaptic D2/D3 autoreceptors at low doses. ENX-104 is in Phase 1 clinical development. About Engrail TherapeuticsEngrail is a clinical-stage pharmaceutical company with a rich pipeline of precision-targeted neuroscience programs designed to improve the lives of patients with neuropsychiatric and neurodevelopmental diseases. ENX-102, a next-generation GABAA positive allosteric modulator, is in Phase 2 clinical development for the treatment of generalized anxiety disorder. ENX-104, a potent dopamine D2/D3 receptor antagonist, is in Phase 1 clinical development for the treatment of major depressive disorder characterized by anhedonia. Additional programs in development are intended to address significant unmet medical needs for the treatment of posttraumatic stress disorder, anxiety-, mood- and stress-related disorders and rare neurological conditions. At Engrail, we apply precision chemistry and pharmacology to develop transformative medicines for patients who are underserved by existing treatments. For more information, visit engrail.com. Media Contact:Anil Vootkur, PharmDEngrail Therapeuticsanil@engrail.com

临床1期临床2期

2024-07-19

·医药观澜

齐鲁制药抗精神病药物「布瑞哌唑口溶膜」申报上市

7月19日，中国国家药监局药品审评中心（CDE）官网公示，齐鲁制药抗精神病药物布瑞哌唑口溶膜已经申报上市并获得受理。布瑞哌唑是一款抗精神病药物，原研药布瑞哌唑片此前已在中国获批上市。此次齐鲁申报的是2.2类口溶膜新剂型。布瑞哌唑（brexpiprazole）为第三代抗精神病药物，其原研药由大冢制药（Otsuka）和灵北（Lundbeck）联合开发。在作用机制上，它是血清素受体5-HT1A和多巴胺受体D2和D3的部分激动剂，也是血清素受体5-HT2A和5-HT2B，以及肾上腺素受体α-1和α-2的部分拮抗剂。对于这些受体，布瑞哌唑表现出高亲和力。布瑞哌唑原研药于2015年7月被美国FDA批准治疗精神分裂症及作为重度抑郁症辅助疗法。2023年5月，FDA宣布批准布瑞哌唑扩展适应症，治疗由阿尔茨海默病引起的痴呆所导致的激越症状。在中国，布瑞哌唑片于2024年6月获批上市，用于治疗精神分裂症。公开资料显示，口溶膜具有使用方便，不需要用水送服，置于舌上可迅速溶解等优点，适合儿童、老年患者和吞咽困难的患者服用，能提高患者的顺应性。根据齐鲁制药公开资料，该公司此前已有5款口溶膜产品上市。参考资料： [1] 中国国家药监局药品审评中心官网. Retrieved Jul 19, 2024, from https://www.cde.org.cn/main/xxgk/listpage/da6efd086c099b7fc949121166f0130c [2]《济南日报》：求“新”求变以“质”致远齐鲁制药助推生物医药产业新质生产力持续“上新”. Retrieved Jul 02, 2024, from https://mp.weixin.qq.com/s/BDOdiCvxYLJ-9UAfCz-yUQ 内容来源于网络，如有侵权，请联系删除。