佐替平(Zotepine) - 药物靶点：5-HT2A receptor x D2 receptor x DRDs_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

Lodopin、Nipolept、Zoleptil

+ [6]

靶点

5-HT2A receptor x D2 receptor x DRDs

作用机制

5-HT2A receptor拮抗剂(5-羟色胺2A受体拮抗剂)、D2 receptor拮抗剂(多巴胺D2受体拮抗剂)、DRDs拮抗剂(多巴胺受体家族拮抗剂)

治疗领域

其他疾病

在研适应症

精神分裂症

非在研适应症-

原研机构

LTL Pharma Co., Ltd.

在研机构

Astellas Pharma, Inc.

Yungjin Pharm. Co., Ltd.

LTL Pharma Co., Ltd.

+ [1]

非在研机构-

最高研发阶段批准上市

首次获批日期

日本 (1981-12-07),

精神分裂症

最高研发阶段(中国)-

特殊审评-

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结构

分子式C18H18ClNOS

InChIKeyHDOZVRUNCMBHFH-UHFFFAOYSA-N

CAS号26615-21-4

关联

4

项与佐替平相关的临床试验

JPRN-UMIN000037989 / CompletedIIT

Efficacy and safety of zotepine in critically ill patients with agitation: A prospective, cohort observational study - Efficacy and safety of zotepine in critically ill patients with agitation: A prospective, cohort observational study

开始日期2015-08-01

申办/合作机构-

NCT01498770 / CompletedN/A

An Observational Drug Utilization Study of SYCREST^® (Asenapine) in the United Kingdom

This study is designed to describe asenapine prescribing patterns in the United Kingdom (UK) during the post-approval period under conditions of usual practice. The use of asenapine in Bipolar Disorder and other indications will be described. To provide epidemiological and clinical perspective, use of aripiprazole and other comparator drugs will be described.

开始日期2013-04-01

申办/合作机构

Organon & Co.

NCT00622011 / Terminated临床4期IIT

Risperidone and Zotepine in the Treatment of Delirium

Delirium is an organic psychiatric syndrome characterized by fluctuating consciousness and impairment in perception, cognition and behavior. In hospitalized elderly, the prevalence of delirium ranges from 10% to 40%. If untreated, delirium is associated with significant morbidity and mortality. Treatment of delirium consists of identifying and managing underlying medical abnormalities and the associated psychiatric symptoms. Conventional antipsychotics have been the mainstay of treatment of agitation and psychosis associated with delirium; but their use is limited in terms of EPS side effects. Second-generation antipsychotic agents have been reported to have a lower incidence of extrapyramidal side effects and tardive dyskinesia which has resulted in their increased use in the treatment of delirious patients. However, there is still no consensus regarding standard pharmacologic treatment of this syndrome that takes use of second-generation antipsychotic agents into account.
Risperidone and zotepine have a lower incidence of EPS and are effective in treating disturbing psychotic behaviors. We hope to compare the efficacy and safety of risperidone and zotepine in the treatment of delirium and the correlation between the severity of delirium with autonomic dysfunction.

开始日期2008-01-01

申办/合作机构

財團法人彰化基督教醫院

100 项与佐替平相关的临床结果

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100 项与佐替平相关的转化医学

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100 项与佐替平相关的专利（医药）

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276

项与佐替平相关的文献（医药）

2024-10-18·Molecules (Basel, Switzerland)

Molecular Dynamics (MD) Simulations Provide Insights into the Activation Mechanisms of 5-HT_2A Receptors.

Article

作者: Lu, Yongcheng ; Mezei, Mihaly ; Cui, Meng ; Logothetis, Diomedes E

Recent breakthroughs in the determination of atomic resolution 3-D cryo-electron microscopy structures of membrane proteins present an unprecedented opportunity for drug discovery. Structure-based drug discovery utilizing in silico methods enables the study of dynamic connectivity of stable conformations induced by the drug in achieving its effect. With the ever-expanding computational power, simulations of this type reveal protein dynamics in the nano-, micro-, and even millisecond time scales. In the present study, aiming to characterize the protein dynamics of the 5HT_2A receptor stimulated by ligands (agonist/antagonist), we performed 1 µs MD simulations on 5HT_2A/DOI (agonist), 5HT_2A/GSK215083 (antagonist), and 5HT_2A (APO, no ligand) systems. The crystal structure of 5HT_2A/zotepine (antagonist) (PDB: 6A94) was used to set up the simulation systems in a lipid bilayer environment. We found the monitoring of the ionic lock residue pair (R3.50-E6.30) of 5HT_2A in MD simulations to be a good approximation of the effects of agonists (ionic lock breakage) or antagonists (ionic lock formation) on receptor activation. We further performed analyses of the MD trajectories, including Principal Component Analysis (PCA), hydrogen bond, salt bridge, and hydrophobic interaction network analyses, and correlation between residues to identify key elements of receptor activation. Our results suggest that in order to trigger receptor activation, DOI must interact with 5HT_2A through residues V5.39, G5.42, S5.43, and S5.46 on TM5, inducing significant conformational changes in the backbone angles of G5.42 and S5.43. DOI also interacted with residues W6.48 (toggle switch) and F6.51 on TM6, causing major conformational shifts in the backbone angles of F6.44 and V6.45. These structural changes were transmitted to the intracellular ends of TM5, TM6, and ICL3, resulting in the breaking of the ionic lock and subsequent G protein activation. The studies could be helpful in future design of selective agonists/antagonists for various serotonin receptors (5HT_1A, 5HT_2A, 5HT_2B, 5HT_2C, and 5HT₇) involved in detrimental disorders, such as addiction and schizophrenia.

2024-09-01·Schizophrenia Research

Association of new-onset diabetes mellitus in adults with schizophrenia treated with clozapine versus patients treated with olanzapine, risperidone, or quetiapine: A systematic review and meta-analysis

Review

作者: He, Qi ; Huo, Chunyue ; Liu, Xiyan ; Zhu, Peixin

INTRODUCTIONMany articles suggest that clozapine was strongly associated with a higher incidence of new-onset diabetes mellitus, and the issue has remained unsettled. Many articles have compared clozapine with FGAs, but few have compared clozapine with SGAs. We aimed to compare the risk of new-onset diabetes mellitus in adults with schizophrenia treated with clozapine and other SGAs.METHODSWe conducted a comprehensive search of databases from their inception up until August 26, 2023. The specific databases include PubMed, Embase and others. We included non-randomized controlled trials involving the use of SGAs such as clozapine, olanzapine, risperidone, quetiapine, amisulpride, and zotepine, with a focus on new-onset diabetes mellitus as an outcome. We utilized odds ratio with 95 % credible intervals (95 % CI) as our effect size measures. The study protocol is registered with PROSPERO, number CRD42024511280.RESULTSWe included 7 studies with sufficient data to include in the meta-analysis. A total of eight studies with 641,48 participants met the eligibility criteria. The OR of the incidence rates of new-onset diabetes between clozapine and olanzapine was 0.95 (95 % CI:[0.82-1.09]), between clozapine and risperidone was 1.25 (95 % CI: [1.09-1.44]), between clozapine and quetiapine was 1.44 (95 % CI: [0.92-2.25]).CONCLUSIONIn patients with schizophrenia, clozapine has been found to have a higher rate of new-onset diabetes mellitus compared to risperidone. However, there was no significant difference in incidence rate between clozapine versus olanzapine and quetiapine. These findings can assist clinicians in balancing the risks and benefits of those drugs.

2024-03-01·Neuropsychopharmacology Reports

Factors associated with the initiation of laxative use in the same patients with schizophrenia over a 20‐year period: Retrospective cohort study

Article

作者: Okayasu, Hiroaki ; Yokoyama, Saaya ; Ishikawa, Takaaki ; Takeuchi, Yoshitaka ; Miyazaki, Kensuke ; Komahashi-Sasaki, Hazuki ; Yasui-Furukori, Norio ; Shinozaki, Masataka ; Furukori, Hanako ; Sasaki, Taro ; Kawamata, Yasushi ; Sugawara, Norio ; Sato, Aoi ; Fukasawa, Takashi

AbstractBackgroundConstipation is a common adverse effect of antipsychotics, but little investigation has been conducted. We aimed to address the factors associated with the initiation of laxative use in the same patients with schizophrenia over a 20‐year period.MethodsWe enrolled patients with schizophrenia attending each hospital (n = 14) from April 1, 2021, and retrospectively examined all prescriptions as of April 1, 2016, 2011, 2006, and 2001, every 5 years starting in 2021, for this population. 716 participants with complete data were included in the analysis. The Cochran Q test followed by Bonferroni correction and the Cochran–Armitage trend test were used to determine the differences and trends of the frequency of each laxative. Multivariate logistic regression analysis was performed to assess the factors on the initiation of laxative use over a 20‐year period.ResultsOf the patients, 25.1% were treated with laxatives in 2001, and 34.1% were treated in 2021. The numbers of patients treated with any laxatives significantly differed over the 20‐year period, with a significant increasing trend. In all laxatives, the numbers of patients treated with magnesium oxide, lubiprostone and elobixibat differed with a significant increasing trend. Female sex, age, the total DZP equivalent dose, and the doses of levomepromazine maleate, olanzapine, quetiapine, zotepine, lithium, and carbamazepine in 2021 were significant factors associated with the initiation of laxative use over the 20‐year period.ConclusionsCareful monitoring is needed for patients treated with levomepromazine maleate, olanzapine, quetiapine and zotepine. Optimizing prescriptions according to treatment guidelines could reduce antipsychotic‐induced constipation.

100 项与佐替平相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D01321	佐替平	N05AX11	DB09225

研发状态

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	日本	LTL Pharma Co., Ltd.	1981-12-07

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临床结果

适应症

分期

评价

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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


NCT00418873 (Pubmed \| J Clin Psychopharmacol)	临床4期	急性疾病 \| 精神分裂症	39	Zotepine	構醖鹹醖繭艱構蓋鑰選(鹹網艱製壓鬱齋淵餘壓) = 鹽膚齋觸築鬱衊糧簾夢築糧築廠齋壓鏇襯夢憲 (網範築窪憲積衊範襯鏇 ) 更多	-	2013-12-01
				Risperidone	構醖鹹醖繭艱構蓋鑰選(鹹網艱製壓鬱齋淵餘壓) = 簾顧齋蓋淵餘憲顧襯網築糧築廠齋壓鏇襯夢憲 (網範築窪憲積衊範襯鏇 ) 更多