Landipirdine(Landipirdine) - 药物靶点：5-HT2A receptor x 5-HT6 receptor_在研适应症：帕金森病_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Landipirdine (USAN/INN)

+ [5]

靶点

5-HT2A receptor x 5-HT6 receptor

作用机制

5-HT2A receptor拮抗剂(5-羟色胺2A受体拮抗剂)、5-HT6 receptor拮抗剂(5-羟色胺受体6拮抗剂)

治疗领域

神经系统疾病内分泌与代谢疾病

在研适应症

帕金森病

非在研适应症

认知障碍帕金森病所致痴呆

原研机构

F. Hoffmann-La Roche Ltd.

在研机构

F. Hoffmann-La Roche Ltd.

非在研机构

Acorda Therapeutics, Inc.Biotie Therapies Oy

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/序列

分子式C18H19FN2O3S

InChIKeyMTTHRRVVGMPYQG-ZDUSSCGKSA-N

CAS号1000308-25-7

关联

1

项与 Landipirdine 相关的临床试验

NCT02258152

/ Completed临床2期

SYN120 a Dual 5-HT6/5-HT2A Antagonist Proof of Concept Study to Evaluate Its Safety, Tolerability and Efficacy in Parkinson's Disease Dementia (SYNAPSE)

The purpose of this study placebo-controlled, randomized, double-blind study is to assess the safety and efficacy of SYN120 in patients with Parkinson's disease dementia (PDD) already treated with a stable dose of a cholinesterase inhibitor.

开始日期2014-12-22

申办/合作机构

Biotie Therapies Oy

[+3]

100 项与 Landipirdine 相关的临床结果

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100 项与 Landipirdine 相关的转化医学

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100 项与 Landipirdine 相关的专利（医药）

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5

项与 Landipirdine 相关的文献（医药）

2023-09-01·Parkinsonism & related disorders

Safety, tolerability, and preliminary efficacy of SYN120, a dual 5-HT6/5-HT2A antagonist, for the treatment of Parkinson disease dementia: A randomized, controlled, proof-of-concept trial.

Article

作者: Litvan, Irene ; Eberling, Jamie ; Macklin, Eric ; Videnovic, Aleksandar ; Fernandez, Hubert H ; Weintraub, Daniel ; Schwarzschild, Michael A ; Kenney, Christopher J

BACKGROUNDSYN120 is a dual serotonin receptor (5-HT6/5-HT2A) antagonist hypothesized to improve cognition and psychiatric symptoms.OBJECTIVESWe evaluated the safety, tolerability, and efficacy of SYN120 in patients with Parkinson disease dementia (PDD).METHODSIn a multicenter, double-blind, parallel-group, 16-week phase 2a proof-of-concept trial in PDD with concomitant cholinesterase inhibitor use, eligible patients were randomized to oral SYN120 (100 mg/day) or placebo. Adverse events (AEs), Unified Parkinson's Disease Rating Scale (UPDRS) scores, and discontinuations assessed safety and tolerability. The primary and key secondary efficacy measures were the Cognitive Drug Research (CDR) computerized assessment system Continuity of Attention and Quality of Episodic Memory scores. Other efficacy measures were: Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Alzheimer's Disease Cooperative Study-Clinician's Global Impression of Change (ADCS-CGIC), Brief Penn Parkinson's Daily Activity Questionnaire-15 (PDAQ-15), Scales for Outcomes in Parkinson's Disease-Sleep Scale (SCOPA-Sleep), and Neuropsychiatric Inventory (NPI).RESULTSEighty-two patients were randomized to SYN120 (N = 38) or placebo (N = 44), AEs occurred in 74% and 77% of patients, and treatment discontinuation in both groups was 16%. Nausea and vomiting were more frequent, and motor symptoms (UPDRS) worsened in the SYN120 group. At week 16, the SYN120 and placebo groups did not differ significantly for any cognitive assessment. Cognitive activities of daily living (PDAQ-15) and the NPI-Apathy/Indifference scores improved nominally in the SYN120 group compared with placebo (unadjusted p = 0.029 and 0.028).CONCLUSIONSSYN120 was adequately tolerated, mild worsening of motor symptoms was noted and it did not improve cognition in PDD patients. Its potential benefits for cognitive activities of daily living and apathy warrant further study.REGISTRATIONClinicaltrials.gov as NCT02258152.

2017-05-17·ACS Chemical Neuroscience3区 · 医学

Serotonergic Approaches in Parkinson’s Disease: Translational Perspectives, an Update

3区 · 医学

Review

作者: Fox, Susan H. ; Huot, Philippe ; Sgambato-Faure, Véronique ; McCreary, Andrew C.

Parkinson's disease (PD) has long been seen as a disorder caused by degeneration of the dopaminergic system, leading to the classic motor manifestations of the disease. However, there is now overwhelming evidence that PD is more than a disease merely caused by dopamine depletion. It is well-known that a myriad of other neurotransmitters are affected by the disease process. One such neurotransmitter is serotonin (5-HT). 5-HT has been shown to play a role in several motor and nonmotor manifestations of PD, including tremor, cognition, depression and psychosis. 5-HT also seems to play a critical role in L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia. A breadth of preclinical studies and clinical trials have been conducted that aimed at modulating the 5-HT system in order to alleviate depression, cognitive deficits, psychosis, and dyskinesia. In this Review, we summarize recent advances in the 5-HT field in PD, but with a translational emphasis. We start by presenting a novel nonhuman primate model of PD that presents with dual dopamine and 5-HT lesions. We then present preclinical and clinical data that introduce new concepts, such as the use of biased and partial agonists, as well as molecules recently introduced to the field of PD, such as eltoprazine, pimavanserin, nelotanserin, and SYN-120, to enhance therapeutic benefit while minimizing adverse events, notably on parkinsonian disability.

Neuropsychiatric Disease and Treatment4区 · 医学

<p>Serotonin Type 6 and 7 Receptors as a Novel Therapeutic Target for the Treatment of Schizophrenia</p>

4区 · 医学

ReviewOA

作者: Tsegay, Etsay Weldekidan ; Gufue, Zenawi Hagos ; Hailu, Nigus Alemu ; Demise, Desalegn Getnet

Schizophrenia is a serious disease of the central nervous system that affects a person's ability to think, feel and behave clearly. Even though the pathophysiological hypothesis of the disease is not clearly understood, dysfunction of dopamine, glutamate, serotonin and other neurotransmitters is widely believed to be involved. Serotonin within the synaptic vesicles functions as neurotransmitter and neurohormone in regulation of emotion, learning, memory, hormone release, cognition and motor function. Dysfunction of normal brain activity of serotonin is associated with schizophrenia. The role of serotonin 6 and 7 receptors in schizophrenia, interaction with neurotransmitters and the effect of drugs on those receptors in schizophrenia are the goal of this review. The aim of this review was to provide information for researchers and other scholars to identify the possible intervention points in the management of schizophrenia. The serotonin 6 and 7 receptors are associated with schizophrenia via modulating cyclic adenosine monophosphate, regulation of Fyn kinase and induction of structural plasticity. The above modulatory effects affect cholinergic, dopaminergic, glutamatergic, adrenergic and GABAergic systems. Recently, diverse numbers of selective agonist and antagonist ligands were developed for both receptors. SGS-518, ABT-354, Lu AE58054, SB-742,457, S-518, AVN-211, AVN-322, SYN-114 and SYN-120 are serotonin 6 receptor antagonists and aripiprazole-controlled release serotonin 7 receptor agonists under clinical trial for schizophrenia. Thus, research on novel drugs that act on serotonin 6 and 7 receptors likely facilitates the intervention into schizophrenia patients seeking better quality of life in the future.

100 项与 Landipirdine 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11157	-	-	DB16214

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
帕金森病	临床2期	-	F. Hoffmann-La Roche Ltd.	-
帕金森病所致痴呆	临床1期	美国	Acorda Therapeutics, Inc.	2014-12-22
认知障碍	临床前	美国	Biotie Therapies Oy	-

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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


NCT02258152 (SYNAPSE, CTgov)	临床2期	帕金森病所致痴呆	82	Placebo (Placebo)	齋簾鏇蓋壓願築蓋繭鹽(鹽製鏇齋遞襯築壓憲廠) = 鬱糧齋願齋獵觸蓋壓艱繭觸選鑰蓋願願餘壓觸 (醖憲膚襯糧廠積蓋淵憲, 艱蓋蓋獵範窪淵壓蓋鑰 ~ 醖築簾顧築夢築觸觸構) 更多	-	2019-04-19
				SYN120 (SYN120)	齋簾鏇蓋壓願築蓋繭鹽(鹽製鏇齋遞襯築壓憲廠) = 鹽觸齋積製襯簾餘憲壓繭觸選鑰蓋願願餘壓觸 (醖憲膚襯糧廠積蓋淵憲, 餘餘製齋窪築襯醖製構 ~ 繭鑰網積壓鹽夢鹹壓醖) 更多
MDS2018	临床2期	非典型进行性核上性麻痹	-	SYN120 100 mg daily	鹽選艱憲簾膚選廠簾範(鑰鬱鏇壓築鹹衊淵範觸) = Numerical improvements with SYN120 compared to placebo were also noted for SCOPA-SLEEP nighttime sleep (ES=0.47; p=0.05) 鬱餘艱築膚顧積製網廠 (夢醖簾餘鹹蓋繭齋窪醖 ) 更多	-	2018-10-05
				Placebo
NCT02258152 (SYNAPSE, MDS2018)	临床2期	非典型进行性核上性麻痹	82	SYN120 100 mg daily	襯糧鬱膚顧繭憲鹹網鏇(鏇簾繭廠糧構膚網獵衊) = incidence of nausea and vomiting were two-fold higher with SYN120 積襯淵鹹餘餘鏇襯顧選 (憲選觸淵鬱鹽製鏇鏇遞 ) 更多	不佳	2018-10-05
				Placebo