MK-0249(MK-0249) - 药物靶点：H3 receptor_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

作用方式

反向激动剂

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

神经系统疾病呼吸系统疾病其他疾病+ [1]

在研适应症-

非在研适应症

阿尔茨海默症注意缺陷障碍伴多动认知功能障碍+ [7]

原研机构

Merck Sharp & Dohme Corp.

在研机构-

非在研机构

Merck Sharp & Dohme Corp.Merck GmbH

权益机构-

最高研发阶段终止临床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/序列

分子式C23H24F3N3O2

InChIKeyDDDZBLNULGDPGA-UHFFFAOYSA-N

CAS号862309-06-6

关联

5

项与 MK-0249 相关的临床试验

NCT00874939

/ Terminated临床1期

A Randomized Clinical Trial To Evaluate the Single Dose Acute Effects of MK-0249 and Donepezil On Cognitive Function In Adult Patients With Alzheimer's Disease

This study will evaluate acute symptomatic improvements in cognitive performance in healthy elderly participants with mild-to-moderate Alzheimer's disease. A four-week pilot study will first evaluate the CogState computerized cognitive battery in participants who are not receiving treatment. After completion of the pilot study, participants will be randomized to receive Placebo, Donepezil 5 mg, MK-0249 7.5 mg, and MK-0249 25 mg. After each drug administration the participants will be given the CogState computerized cognitive battery to assess cognitive performance. The primary hypotheses are that cognitive performance in participants with Alzheimer's disease, or in healthy participants, is improved by the administration of a single oral 5 mg dose of Donepezil as compared to placebo.

开始日期2009-04-06

申办/合作机构

Merck Sharp & Dohme Corp.

NCT00620659

/ Terminated临床2期

Phase IIa, Randomized, Double-blind, Placebo-controlled, 3-period Crossover, Adaptive Dose Design, Clinical Trial to Evaluate Safety & Efficacy of MK0249 in Treating Refractory Excessive Daytime Sleepiness in Patients With Obstructive Sleep Apnea/Hypopnea Syndrome Appropriately Using nCPAP Therapy.

The purpose of this study is to determine the safety and efficacy of MK0249 in treating refractory excessive daytime sleepiness (EDS) in patients with Obstructive Sleep Apnea/Hypopnea Syndrome (OSA/HS) using nasal continuous positive airway pressure (nCPAP) therapy.

开始日期2008-02-01

申办/合作机构

Merck Sharp & Dohme Corp.

NCT00506077

/ Completed临床2期

A Phase IIa, Randomized, Double-Blind, Placebo-Controlled, 2-Period, Cross-Over Clinical Trial to Study the Safety and Efficacy of MK0249 for the Treatment of Cognitive Impairment in Patients With Schizophrenia

The purpose of this study is to determine the safety and effectiveness of an investigational drug MK0249 for the treatment of the cognitive impairment in patients with schizophrenia.

开始日期2007-12-01

申办/合作机构

Merck Sharp & Dohme Corp.

100 项与 MK-0249 相关的临床结果

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100 项与 MK-0249 相关的转化医学

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100 项与 MK-0249 相关的专利（医药）

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16

项与 MK-0249 相关的文献（医药）

2014-01-01·Journal of Nuclear Medicine1区 · 医学

¹¹C-MK-8278 PET as a Tool for Pharmacodynamic Brain Occupancy of Histamine 3 Receptor Inverse Agonists

1区 · 医学

Article

作者: de Hoon, Jan ; Han, Lingling ; Iannone, Robert ; Van Laere, Koenraad J. ; Mozley, David P. ; Koole, Michel ; Cerchio, Kristine ; Bormans, Guy ; Van Hecken, Anne ; Plalcza, John ; Burns, Donald H. ; Renger, John ; Hamill, Terence G. ; Hargreaves, Richard J. ; Sanabria-Bohrquez, Sandra M. ; Depre, Marleen ; De Lepeleire, Inge

The histamine 3 (H3) receptor is a presynaptic autoreceptor in the central nervous system that regulates the synthesis and release of histamine and modulates the release of other major neurotransmitters. H3 receptor inverse agonists (IAs) may be efficacious in the treatment of various central nervous system disorders, including excessive daytime sleepiness, attention deficit hyperactivity disorder, Alzheimer disease, ethanol addiction, and obesity.METHODSUsing PET and a novel high-affinity and selective radioligand (11)C-MK-8278, we studied the tracer biodistribution, quantification, and brain H3 receptor occupancy (RO) of MK-0249 and MK-3134, 2 potential IA drugs targeting cerebral H3 receptors, in 6 healthy male subjects (age, 19-40 y). The relationship among H3 IA dose, time on target, and peripheral pharmacokinetics was further investigated in 15 healthy male volunteers (age, 18-40 y) with up to 3 PET scans and 3 subjects per dose level.RESULTSThe mean effective dose for (11)C-MK-8278 was 5.4 ± 1.1 μSv/MBq. Human brain kinetics showed rapid high uptake and fast washout. Binding potential values can be assessed using the pons as a reference region, with a test-retest repeatability of 7%. Drug RO data showed low interindividual variability per dose (mean RO SD, 2.1%), and a targeted 90% RO can be reached for both IAs at clinically feasible doses.CONCLUSION(11)C-MK-8278 is a useful novel PET radioligand for determination of human cerebral H3 receptor binding and allows highly reproducible in vivo brain occupancy of H3-targeting drugs, hereby enabling the evaluation of novel compounds in early development to select doses and schedules.

2013-10-01·Sleep Medicine3区 · 医学

Alertness and psychomotor performance effects of the histamine-3 inverse agonist MK-0249 in obstructive sleep apnea patients on continuous positive airway pressure therapy with excessive daytime sleepiness: a randomized adaptive crossover study

3区 · 医学

Article

作者: Thomas Roth ; Paulette Ceesay ; David Michelson ; Ellen Snyder ; Jill Hutzelmann ; W. Joseph Herring ; Kenneth Liu ; Duane Snavely ; Christopher Lines

OBJECTIVESWe aimed to evaluate the efficacy of the selective H3 receptor inverse agonist MK-0249 to treat excessive daytime sleepiness (EDS).METHODSIn this three-period, double-blind, crossover study, 125 patients (100 men, 25 women; mean age, 48.6 years) with obstructive sleep apnea receiving nasal continuous positive airway pressure therapy who had refractory EDS were randomized to 2 weeks each of daily MK-0249 (5, 8, 10, or 12 mg, adaptively assigned), modafinil 200 mg, and placebo. At baseline and after each treatment period, six maintenance of wakefulness tests (MWT) and Psychomotor Vigilance Tasks (PVT) were conducted at 2-h intervals, beginning 1h postdose (∼09:00). The Epworth sleepiness scale (ESS), Clinical Global Impression of Severity (CGIS) and Digit Symbol Substitution Test (DSST) also were assessed. The primary end point was MWT sleep latency averaged over the first four time points (MWT-early).RESULTSMWT-early mean change from baseline sleep latency at week 2 was 1.2 min for placebo, 2.1 min for MK-0249 (top two doses pooled; P>.05 vs. placebo), and 5.9 min for modafinil (P < or = .001 vs. placebo). MK-0249 showed improvements vs placebo on secondary and exploratory end points of ESS, CGIS, PVT, and DSST. Insomnia adverse events (AEs) were greater for MK-0249 (combined doses, 17.5%) than for placebo (0.9%) or modafinil (1.8%).CONCLUSIONMK-0249 did not significantly affect MWT sleep latency. However, the pattern of improvement on subjective ratings and psychomotor performance end points suggested that MK-0249 was associated with changes in aspects of cognition and performance not captured by the MWT.

2013-05-01·Schizophrenia Research2区 · 医学

Randomized crossover study of the histamine H3 inverse agonist MK-0249 for the treatment of cognitive impairment in patients with schizophrenia

2区 · 医学

Article

作者: Michael F. Egan ; Regina Gottwald ; Xin Zhao ; David Michelson ; Ying Zhang ; Duane Snavely ; Christopher Lines ; Lyn Harper-Mozley

BACKGROUNDCurrent antipsychotic treatments have little impact on the cognitive deficits associated with schizophrenia. It has been proposed that agents which promote histamine release may enhance cognition. We evaluated whether the H3 inverse agonist MK-0249 might improve cognitive deficits in patients with schizophrenia.METHODSOutpatients (N=55) with schizophrenia between ages 21 and 55 who were clinically stable, experienced no more than mild to moderate overall symptoms (PANSS score total 36-75), and were taking a stable dose of antipsychotic medication were randomized to MK-0249 10mg and placebo in a multi-center, randomized, double-blind, 2-period (4-weeks per period), cross-over study. The primary efficacy endpoint was the mean change from baseline at 4-weeks of treatment in the total cognitive score on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery. Other assessments of cognition were also performed.RESULTSA total of 46 patients completed the study. MK-0249 10mg did not demonstrate a statistically significant difference compared to placebo in the mean change from baseline in the total cognitive score on the BACS battery after 4-weeks of treatment (-0.1, 95% CI: -2.3, 2.1) or with regard to secondary measures of attention/processing speed, episodic memory, or working memory after 4-weeks of treatment. The incidence of adverse events was greater during the MK-0249 treatment period (25/52 patients, 48.1%) compared to the placebo treatment period (15/51 patients, 29.4%).CONCLUSIONMK-0249 10mg once daily was not superior to placebo in the treatment of cognitive impairment in patients with schizophrenia after 4-weeks. (Clinicaltrials.gov: NCT00506077).

100 项与 MK-0249 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11910

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
白天过度嗜睡	临床2期	-	Merck Sharp & Dohme Corp.	2008-02-01
阻塞性睡眠呼吸暂停低通气综合征	临床2期	-	Merck Sharp & Dohme Corp.	2008-02-01
认知功能障碍	临床2期	-	Merck Sharp & Dohme Corp.	2007-12-01
偏执型精神分裂症	临床2期	-	Merck Sharp & Dohme Corp.	2007-12-01
阿尔茨海默症	临床2期	美国	Merck GmbH	-
阿尔茨海默症	临床2期	美国	Merck GmbH	-
注意缺陷障碍伴多动	临床2期	美国	Merck GmbH	-
注意缺陷障碍伴多动	临床2期	美国	Merck GmbH	-
精神分裂症	临床2期	美国	Merck GmbH	-
睡眠呼吸暂停综合征	临床2期	美国	Merck GmbH	-

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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


NCT00506077 (0249-016, CTgov)	临床2期	认知功能障碍 \| 偏执型精神分裂症	55	MK0249 (MK0249)	選繭鬱積壓鑰獵憲選蓋(醖壓製製網積繭憲蓋糧) = 糧遞餘繭選蓋構簾構壓鹽鏇願廠積蓋製願製膚 (餘壓鬱蓋膚鏇鹹壓艱蓋, 憲艱選衊簾築簾鏇襯選 ~ 築願醖鏇窪網顧窪鑰構) 更多	-	2011-03-07
				Comparator: Placebo (unspecified) (Placebo)	選繭鬱積壓鑰獵憲選蓋(醖壓製製網積繭憲蓋糧) = 觸製餘醖簾齋襯製鬱構鹽鏇願廠積蓋製願製膚 (餘壓鬱蓋膚鏇鹹壓艱蓋, 壓淵齋網網鏇淵襯鏇簾 ~ 積襯壓衊範鏇築窪製鹽) 更多
NCT00475735 (0249-018, CTgov)	临床2期	注意缺陷障碍伴多动	72	MK0249 (MK-0249)	餘鹹鹹廠蓋齋艱願選觸(繭衊遞襯顧鏇願網齋繭) = 願顧範遞製夢獵憲鑰簾醖憲鏇顧齋範膚蓋廠鹹 (鹽廠製觸廠鏇壓製衊廠, 齋鹹夢糧齋網夢蓋憲鹹 ~ 鬱廠築製襯繭艱鏇顧齋) 更多	-	2010-12-10
				Concerta (methylphenidate) (Concerta)	餘鹹鹹廠蓋齋艱願選觸(繭衊遞襯顧鏇願網齋繭) = 獵鏇齋壓鏇網積膚範淵醖憲鏇顧齋範膚蓋廠鹹 (鹽廠製觸廠鏇壓製衊廠, 糧鹽齋遞鑰繭鬱觸淵襯 ~ 簾醖鹹襯膚範願衊蓋餘) 更多
NCT00420420 (0249-011, CTgov)	临床2期	阿尔茨海默症	144	Comparator: Placebo (unspecified)	淵糧廠網壓衊簾鹹獵淵(鬱膚艱糧鹽糧網齋簾淵) = 淵襯壓願顧艱網廠淵廠鑰餘遞積醖壓鑰範網繭 (廠餘夢獵艱願網膚夢蓋, 鹹壓願糧夢遞醖顧廠夢 ~ 餘艱顧築淵製窪鹹艱構) 更多	-	2010-11-18