Samelisant(Samelisant) - 药物靶点：H3 receptor_在研适应症：猝倒症，发作性睡病，认知功能障碍_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拮抗剂(组胺H3受体拮抗剂)

治疗领域

神经系统疾病其他疾病

在研适应症

猝倒症发作性睡病认知功能障碍

非在研适应症-

原研机构

Suven Life Sciences Ltd.

在研机构

Suven Life Sciences Ltd.

非在研机构-

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C21H31N3O3

InChIKeyLNXDUSQEXVQFGP-UHFFFAOYSA-N

CAS号1394808-82-2

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关联

4

项与 Samelisant 相关的临床试验

NCT04072380 / Completed临床2期

A Phase 2, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of 2 mg and 4 mg SUVN-G3031 Compared to Placebo in Patients With Narcolepsy With and Without Cataplexy

This study is of an investigational drug called SUVN-G3031 (Samelisant) as a possible treatment for narcolepsy with cataplexy or narcolepsy without cataplexy. The main purpose of this study is to learn how well the study drug works and how safe the study drug is compared to placebo.

开始日期2019-09-21

申办/合作机构

Suven Life Sciences Ltd.

NCT02881294 / Completed临床1期

A Phase I, Single-center, Open-label, Single-dose Study to Evaluate the Effect of Food, Gender, and Age on the Pharmacokinetic Profile of Orally Administered SUVN-G3031 in Healthy Subjects

The purpose of the study is to investigate the effect of Food, Gender, and Age on the Pharmacokinetic Profile of SUVN-G3031 in Healthy Subjects

开始日期2016-08-01

申办/合作机构

Suven Life Sciences Ltd.

NCT02342041 / Completed临床1期

A Single-center, Double-blind, Placebo-controlled, Randomized, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of SUVN-G3031 After Single Ascending Doses and Multiple Ascending Doses in Healthy Male Subjects

The purpose of this study is to investigate the safety, tolerability and pharmacokinetics of SUVN-G3031 in healthy male subjects following single or multiple ascending doses.

开始日期2014-09-01

申办/合作机构

Suven Life Sciences Ltd.

100 项与 Samelisant 相关的临床结果

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100 项与 Samelisant 相关的转化医学

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100 项与 Samelisant 相关的专利（医药）

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6

项与 Samelisant 相关的文献（医药）

2021-06-01·Psychopharmacology3区 · 医学

Samelisant (SUVN-G3031), a potent, selective and orally active histamine H3 receptor inverse agonist for the potential treatment of narcolepsy: pharmacological and neurochemical characterisation

3区 · 医学

Article

作者: Jasti, Venkat ; Badange, Rajesh ; Subramanian, Ramkumar ; Benade, Vijay ; Daripelli, Saivishal ; Shinde, Anil ; Petlu, Surendra ; Jayarajan, Pradeep ; Kamuju, Venkatesh ; Muddana, Nageswara Rao ; Bhyrapuneni, Gopinadh ; Nirogi, Ramakrishna ; Mekala, Venkat Reddy

RATIONALESamelisant (SUVN-G3031) is a potent and selective histamine H3 receptor (H3R) inverse agonist with good brain penetration and oral bioavailability.OBJECTIVESPharmacological and neurochemical characterisation to support the utility of Samelisant (SUVN-G3031) in the treatment of sleep-related disorders like narcolepsy.METHODSSamelisant (SUVN-G3031) was tested in rat brain microdialysis studies for evaluation of modulation in histamine, dopamine and norepinephrine. Sleep EEG studies were carried out in orexin knockout mice to study the effects of Samelisant (SUVN-G3031) on the sleep-wake cycle and cataplexy.RESULTSSamelisant (SUVN-G3031) has a similar binding affinity towards human (hH3R; K_i = 8.7 nM) and rat (rH3R; K_i = 9.8 nM) H3R indicating no inter-species differences. Samelisant (SUVN-G3031) displays inverse agonist activity and it exhibits very high selectivity towards H3R. Samelisant (SUVN-G3031) treatment in mice produced a dose-dependent increase in tele-methylhistamine levels indicating the activation of histaminergic neurotransmission. Apart from increasing the levels of histamine, Samelisant (SUVN-G3031) also modulates dopamine and norepinephrine levels in the cerebral cortex while it has no effects on dopamine levels in the striatum or nucleus accumbens. Treatment with Samelisant (SUVN-G3031; 10 and 30 mg/kg, p.o.) produced a significant increase in wakefulness with a concomitant decrease in NREM sleep in orexin knockout mice subjected to sleep EEG. Samelisant (SUVN-G3031) also produced a significant decrease in Direct REM sleep onset (DREM) episodes, demonstrating its anticataplectic effects in an animal model relevant to narcolepsy. Modulation in cortical levels of histamine, norepinephrine and dopamine provides the neurochemical basis for wake-promoting and anticataplectic effects observed in orexin knockout mice.CONCLUSIONSPre-clinical studies of Samelisant (SUVN-G3031) provide a strong support for utility in the treatment of sleep-related disorders related to EDS and is currently being evaluated in a phase 2 proof of concept study in the USA for the treatment of narcolepsy with and without cataplexy.

2021-06-01·Journal of Psychopharmacology3区 · 医学

Histamine 3 receptor inverse agonist Samelisant (SUVN-G3031): Pharmacological characterization of an investigational agent for the treatment of cognitive disorders

3区 · 医学

Article

作者: Shinde, Anil ; Ganuga, Narender ; Jayarajan, Pradeep ; Petlu, Surendra ; Manoharan, Arunkumar ; Bhyrapuneni, Gopinadh ; Jasti, Venkat ; Medapati, Rajesh B ; Subramanian, Ramkumar ; Abraham, Renny ; Badange, Rajesh K ; Benade, Vijay ; Nirogi, Ramakrishna ; Grandhi, Venkata R ; Gandipudi, Sudhakar

Background: Central histamine H3 receptors are a family of presynaptic auto and heteroreceptors. Blockade of the presynaptic H3 receptors activates the downstream pathway(s) involved in the processes of learning and memory, making it a potential therapeutic option for ameliorating cognitive dysfunction. Samelisant (SUVN-G3031) is a potent and selective inverse agonist at the H3 receptors. Aim: The aim of this research is to study the effects of Samelisant in diverse animal models of cognitive functions. Methods: The effects of Samelisant on cognitive functions were studied using social recognition, object recognition and Morris water maze tasks. Neurochemical and electrophysiological effects of Samelisant were monitored using microdialysis and electroencephalography techniques. Results: Samelisant showed procognitive effects in diverse animal models of cognition at doses ranging from 0.3 to 3 mg/kg, per os ( p.o.) (social recognition and object recognition task). Samelisant significantly increased the brain acetylcholine levels in the cortex at doses of 10 and 20 mg/kg, p.o. In the Morris water maze task, combined administration of suboptimal doses of Samelisant and donepezil resulted in procognitive effects significantly larger than the either treatment. Similarly, Samelisant significantly potentiated the effects of donepezil on pharmacodynamic biomarkers of cognition i.e. acetylcholine levels in brain and neuronal theta oscillations. Conclusion: Samelisant may have potential utility in the treatment of cognitive deficits associated with hypocholinergic state.

2020-09-01·European Journal of Pharmaceutical Sciences2区 · 医学

Absorption, distribution, metabolism, excretion (ADME), drug-drug interaction potential and prediction of human pharmacokinetics of SUVN-G3031, a novel histamine 3 receptor (H3R) inverse agonist in clinical development for the treatment of narcolepsy

2区 · 医学

Article

作者: Padala, Nagasurya Prakash ; Palacharla, Veera Raghava Chowdary ; Manoharan, Arunkumar ; Shinde, Anil K ; Bhyrapuneni, Gopinadh ; Ajjala, Devender Reddy ; Nirogi, Ramakrishna ; Muddana, Nageswara Rao ; Mohammed, Abdul Rasheed ; Subramanian, Ramkumar

SUVN-G3031 is a potent and selective inverse agonist of Histmine-3 (H₃) receptor that is being investigated for the treatment of narcolepsy. SUVN-G3031 has high passive permeability, not a substrate for P-glycoprotein, has high plasma unbound fractions and was equally distributed between blood and plasma. Major routes of metabolism in vitro were cyclization (Metabolite A) in microsomes and dealkylation (Metabolite D) in hepatocytes. Intrinsic clearance in liver microsomes and hepatocytes was low as monitored by metabolite formation approach. CYP3A4 and MAO-A were the major enzymes involved in the formation of metabolite A and metabolite D respectively. The human hepatic clearance estimated by well-stirred model from hepatocytes was low (2.7 L.h ^-¹) illustrating the importance of metabolite formation kinetics for prediction of human clearance for SUVN-G3031. Renal clearance in humans (9.7 L.h ^-¹) was predicted from dog renal clearance and accounts for ~78% of the total clearance. SUVN-G3031 was neither an inhibitor nor inducer of the P450 enzymes at clinically relevant concentrations. SUVN-G3031 did not inhibit the major uptake transporters and was not a substrate for the uptake transporters. The potential of SUVN-G3031 as a victim and perpetrator of drug-drug interactions is remote. The predicted human pharmacokinetic parameters were consistent with those observed in the first-in-human study.

100 项与 Samelisant 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14835

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
猝倒症	临床2期	加拿大	Suven Life Sciences Ltd.	2019-09-21
猝倒症	临床2期	美国	Suven Life Sciences Ltd.	2019-09-21
发作性睡病	临床2期	-	Suven Life Sciences Ltd.	-
认知功能障碍	临床1期	美国	Suven Life Sciences Ltd.	-
认知障碍	药物发现	美国	Suven Life Sciences Ltd.	2014-09-01

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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


NCT02342041 \| NCT04072380 (Pubmed \| Clin Drug Investig)	N/A	发作性睡病	-	SUVN-G3031	艱齋餘觸構壓衊範醖獵(選蓋鏇繭遞廠鹹壓餘願) = 鏇選廠鑰齋製糧鑰窪鏇選觸鬱網繭夢簾鹽鹽壓 (窪鹽餘鹽積淵獵膚鏇觸 )	-	2020-07-01
NCT04072380 (SUVN-G3031, WSC2019)	临床2期	发作性睡病	-	SUVN-G3031	製選願蓋構憲願窪壓繭(醖襯構憲蓋鏇選顧餘夢) = indicated superior wake promoting profile of SUVN-G3031 簾蓋蓋鹽膚鏇蓋築觸壓 (鹹鬱醖鏇顧膚蓋窪製襯 ) 更多	积极	2019-09-20
SUVN-G3031 (AAIC2014)	N/A	认知功能障碍	-	SUVN-G3031	夢積選齋網築夢淵糧餘(襯醖淵網鏇廠鹹齋壓願) = 艱範窪遞觸鏇願齋艱選鹹淵鹽願醖糧積廠積積 (壓築構鏇膚鏇獵範願窪 ) 更多	-	2014-07-01