AZD-5213(AZD-5213) - 药物靶点：H3 receptor_在研适应症：阿尔茨海默症，轻度认知障碍_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

H3 receptor

作用机制

H3 receptor反向激动剂(组胺H3受体反向激动剂)

治疗领域

神经系统疾病其他疾病

在研适应症

阿尔茨海默症轻度认知障碍

非在研适应症

糖尿病性神经病变疼痛Tourette 综合征

原研机构

AstraZeneca PLC

在研机构

AstraZeneca, Inc.

非在研机构

AstraZeneca PLC

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C19H25N3O2

InChIKeyVCQZCDSEWSFTPO-SJORKVTESA-N

CAS号1119807-02-1

关联

7

项与 AZD-5213 相关的临床试验

NCT01928381 / Completed临床2期

A Randomized, Double-Blind, Placebo-Controlled Crossover Study to Evaluate the Preliminary Efficacy of AZD5213 in Combination With Pregabalin in Subjects With Painful Diabetic Neuropathy and Good Pain Reporting Ability

This is a 2-part study. In Part 1 of the study, subjects will undergo a pain reporting training program in which a painful stimulus will be applied to the subject's hand, and the subjects will be asked to report how painful the stimulus is. Over the course of the pain training sessions, feedback will be provided to the subject about how accurately they are reporting their degree of pain, relative to the amount of pressure stimulus applied to evoke pain. Those subjects who have adequate pain reporting ability will be asked to continue into Part 2 of the study in which 3 different blinded study drugs will be administered to each subject, in a crossover design to compare whether or not the study drugs improve pain associated with diabetic neuropathy.

开始日期2013-11-01

申办/合作机构

AstraZeneca PLC

NCT01904773 / Completed临床2期

A 6-month, Multicenter, Randomized, Safety, Tolerability, Pharmacokinetic, and Preliminary Efficacy Study of AZD5213 in Adolescents With Tourette's Disorder

This is a two-part, randomized, multi-center, blinded study in adolescents with Tourette's Disorder. There will be an up to 21-day screening period in which subject eligibility will be determined. In Part 1 of the study, the safety, tolerability and pharmacokinetics of AZD5213 will be assessed during a 1- week period.
In Part 2 of the study, the safety, tolerability, and preliminary efficacy of two doses (depending on tolerability in Part 1 of the study) of AZD5213 and placebo will be assessed through six consecutive four-week crossover periods. Each subject will receive both AZD5213 and placebo. A follow-up vist will take place at 14 (±) 7 days following the last dose of study drug.

开始日期2013-08-01

申办/合作机构

AstraZeneca PLC

NCT01548287 / Completed临床2期

A Phase IIa Safety and Tolerability Study to Investigate the Effect on Sleep of 3 Doses of AZD5213 and Placebo in Patients With Mild Alzheimer's Disease and Mild Cognitive Impairment During 4 Weeks of Treatment, Placebo-Controlled

This is a study where AZD5213 or placebo is given to patients with Mild Alzheimer's Disease or Mild Cognitive Impairment in a blinded and random assignment. The main study objective is to estimate the relationship of sleep duration versus dose after 4 weeks of treatment.

开始日期2012-04-01

申办/合作机构

AstraZeneca PLC

100 项与 AZD-5213 相关的临床结果

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100 项与 AZD-5213 相关的转化医学

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100 项与 AZD-5213 相关的专利（医药）

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3

项与 AZD-5213 相关的文献（医药）

2021-01-01·The Clinical Journal of Pain3区 · 医学

A 3-way Cross-over Study of Pregabalin, Placebo, and the Histamine 3 Receptor Inverse Agonist AZD5213 in Combination With Pregabalin in Patients With Painful Diabetic Neuropathy and Good Pain-reporting Ability

3区 · 医学

Article

作者: Katz, Nathaniel ; Raudibaugh, Karen ; Alexander, Robert C ; Spierings, Egilius L H

Objectives:In this study, patients with painful diabetic neuropathy were trained using an experimental pain paradigm in an attempt to enroll a subset of patients who are “pain connoisseurs” and therefore more able to discriminate between active and placebo treatments.Methods:AZD5213, a novel histamine H3 receptor inverse agonist+pregabalin, pregabalin, and placebo were then tested in a 3-period cross-over.Results:The study did not provide any evidence of clinical efficacy for AZD5213 when combined with pregabalin in the treatment of painful diabetic neuropathy.Discussion:The training of study patients in pain reporting and subsequent enrichment with good pain reporters also did not enable the robust detection of the efficacy of pregabalin relative to placebo in a small sample size. Further work is required before recommending the use of “connoisseur” patients in future neuropathic pain studies.

2013-07-01·International Journal of Neuropsychopharmacology2区 · 医学

AZD5213: a novel histamine H3 receptor antagonist permitting high daytime and low nocturnal H3 receptor occupancy, a PET study in human subjects

2区 · 医学

ArticleOA

作者: Segerdahl, Märta ; Stenkrona, Per ; Jucaite, Aurelija ; Takano, Akihiro ; Jostell, Karl-Gustav ; Nyberg, Svante ; Halldin, Christer ; Boström, Emma

AbstractThe histamine H3 receptor represents an appealing central nervous system drug target due to its important role in the neurobiology of cognition and wake-sleep regulation. The therapeutic benefit of H3 antagonists/inverse agonists may be hampered by disruption of sleep that has been observed in humans with prolonged high H3 receptor occupancy (H3RO), extending into night-time. AZD5213 is a highly selective H3 antagonist (in vitro inverse agonist) developed to achieve a pharmacokinetic profile permitting circadian fluctuations of H3RO. Its efficacy has been demonstrated in rodent behavioural models of cognition. In human subjects, AZD5213 was safe and well tolerated following repeated doses (1–14 mg/d) and demonstrated a short (∼5 h) half-life. In this PET study H3RO was measured using the radioligand [11C]GSK189254 ([11C]AZ12807110) in seven young male volunteers following single doses of AZD5213 (0.05–30 mg). H3RO was calculated using the Lassen plot method. The plasma concentrations and the affinity constant (Ki,pl 1.14 nmol/l, corresponding to the plasma concentration required to occupy 50% of available receptors) were used to estimate the H3RO time-course. AZD5213 showed dose and concentration dependent H3RO ranging from 16 to 90%. These binding characteristics and the pharmacokinetic profile of AZD5213 indicate that high daytime and low night-time H3RO could be achieved following once daily oral dosing of AZD5213. Fluctuations of H3RO following circadian rhythm of the histamine system may be expected to reduce the risk of sleep disruption while maintaining daytime efficacy. AZD5213 may thus be an optimal compound to evaluate the clinical benefit of selective H3 antagonism in cognitive disorders.

ChemBioChem

Discovery of 18F Labeled AZD5213 Derivatives as Novel Positron Emission Tomography (PET) Radioligands Targeting Histamine Subtype‐3 Receptor

Article

作者: Collier, Lee ; Mühlfenzl, Kim S. ; Zhai, Chuangyan ; Zhou, Xin ; Zhao, Chunyu ; Dahl, Kenneth ; Patel, Jimmy S. ; Liang, Steven ; Gao, Yabiao ; Rong, Jian ; Sun, Zhenkun ; Song, Zhendong ; Elmore, Charles S. ; Ran, Chongzhao ; Chen, Jiahui ; Yuan, Hongjie ; Zhang, Linqi ; Chaudhary, Ahmad ; Schou, Magnus ; Haider, Ahmed ; Li, Yinlong

The histamine subtype 3 (H3) receptor is an important drug target in the central nervous system (CNS), and PET imaging offers a promising technique for the noninvasive evaluation of CNS disease related to the H3 receptor. In this study, we synthesized and evaluated the binding effects of [18F]H3‐2404 and [18F]H3‐2405 by modifying the structure of AZD5213, a selective H3 antagonist. These two radioligands were prepared in high radiochemical yields and displayed stability in serum. The in vitro autoradiographic study in rat brain tissue and the following in vivo PET studies in mice demonstrated sufficient brain uptake but predominantly non‐specific distribution in rodent brain. Although these data suggest that [18F]H3‐2404 and [18F]H3‐2405 are unsuitable as PET tracers for brain imaging of the H3 receptor, this study provides a valuable attempt for optimizing 18F labeled radiotracers based on AZD5213.

100 项与 AZD-5213 相关的药物交易

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研发状态

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
阿尔茨海默症	临床2期	美国	AstraZeneca, Inc.	2013-07-01
轻度认知障碍	临床2期	美国	AstraZeneca, Inc.	2013-07-01
糖尿病性神经病变	药物发现	美国	AstraZeneca PLC	2013-11-01
疼痛	药物发现	美国	AstraZeneca PLC	2013-11-01
Tourette 综合征	药物发现	美国	AstraZeneca PLC	2013-08-01

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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


NCT01194986 (Pubmed \| Int J Neuropsychopharmacol)	临床1期	-	13	AZD5213	夢網憲餘膚鹽簾網憲窪(簾網窪衊積簾範製襯簾) = 衊顧糧齋構糧夢蓋鬱構築鹹衊襯鬱壓膚構壓鹽 (願窪鏇齋鬱壓範糧顧衊 )	-	2013-07-01