文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

BINA 通过正变构调节 mGluR,可减轻 MPTP 损毁恒河猴的运动障碍和精神病样行为。

Positive allosteric mGluR modulation with BINA alleviates dyskinesia and psychosis-like behaviours in the MPTP-lesioned marmoset.

机构信息

Neurodegenerative Disease Group, Montreal Neurological Institute-Hospital (The Neuro), Montreal, QC, Canada.

Comparative Medicine & Animal Resource Centre, McGill University, Montreal, QC, Canada.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2024 Nov;397(11):8917-8924. doi: 10.1007/s00210-024-03215-3. Epub 2024 Jun 11.


DOI:10.1007/s00210-024-03215-3
PMID:38861009
Abstract

There is mounting evidence that positive allosteric modulation of metabotropic glutamate type 2 receptors (mGluR) is an efficacious approach to reduce the severity of L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia, psychosis-like behaviours (PLBs), while conferring additional anti-parkinsonian benefit. However, the mGluR positive allosteric modulators (PAMs) tested so far, LY-487,379 and CBiPES, share a similar chemical scaffold. Here, we sought to assess whether similar benefits would be conferred by a structurally-distinct mGluR PAM, biphenylindanone A (BINA). Six 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned marmosets exhibiting dyskinesia and PLBs were administered L-DOPA with either vehicle or BINA (0.1, 1, and 10 mg/kg) in a randomised within-subject design and recorded. Behaviour was analysed by a blinded rater who scored the severity of each of parkinsonism, dyskinesia and PLBs. When added to L-DOPA, BINA 0.1 mg/kg, 1 mg/kg, and 10 mg/kg all significantly reduced the severity of global dyskinesia, by 40%, 52% and 53%, (all P < 0.001) respectively. BINA similarly attenuated the severity of global PLBs by 35%, 48%, and 50%, (all P < 0.001) respectively. Meanwhile, BINA did not alter the effect of L-DOPA on parkinsonism exhibited by the marmosets. The results of this study provide incremental evidence of positive allosteric modulation of mGluR as an effective therapeutic strategy for alleviating dyskinesia and PLBs, without hindering the anti-parkinsonian action of L-DOPA. Furthermore, this therapeutic benefit does not appear to be confined to a particular chemical scaffold.

摘要

越来越多的证据表明,代谢型谷氨酸受体 2(mGluR)的正变构调节是一种有效的方法,可以减轻 L-3,4-二羟基苯丙氨酸(L-DOPA)诱导的运动障碍、类精神病行为(PLBs)的严重程度,同时提供额外的抗帕金森益处。然而,迄今为止测试的 mGluR 正变构调节剂(PAMs),LY-487,379 和 CBiPES,具有相似的化学结构。在这里,我们试图评估结构不同的 mGluR PAM,双苯并吲哚酮 A(BINA)是否会带来类似的益处。六只患有运动障碍和 PLBs 的 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)损伤的狨猴,以随机、自身对照的方式接受 L-DOPA 与载体或 BINA(0.1、1 和 10mg/kg)联合治疗,并进行记录。行为由一名盲法评分者进行分析,他对帕金森病、运动障碍和 PLBs 的严重程度进行评分。当添加到 L-DOPA 时,BINA 0.1mg/kg、1mg/kg 和 10mg/kg 分别显著降低了整体运动障碍的严重程度,分别降低了 40%、52%和 53%(均 P<0.001)。BINA 同样分别降低了整体 PLBs 的严重程度,降低了 35%、48%和 50%(均 P<0.001)。同时,BINA 并未改变 L-DOPA 对狨猴帕金森病的作用。这项研究的结果提供了代谢型谷氨酸受体 2 的正变构调节作为减轻运动障碍和 PLBs 的有效治疗策略的额外证据,而不会阻碍 L-DOPA 的抗帕金森作用。此外,这种治疗益处似乎并不局限于特定的化学结构。

相似文献

[1]
Positive allosteric mGluR modulation with BINA alleviates dyskinesia and psychosis-like behaviours in the MPTP-lesioned marmoset.

Naunyn Schmiedebergs Arch Pharmacol. 2024-11

[2]
Additive effects of mGluR positive allosteric modulation, mGluR orthosteric stimulation and 5-HTR antagonism on dyskinesia and psychosis-like behaviours in the MPTP-lesioned marmoset.

Naunyn Schmiedebergs Arch Pharmacol. 2021-12

[3]
Selective metabotropic glutamate receptor 2 positive allosteric modulation alleviates L-DOPA-induced psychosis-like behaviours and dyskinesia in the MPTP-lesioned marmoset.

Eur J Pharmacol. 2020-1-28

[4]
Effect of the mGlu positive allosteric modulator CBiPES on dyskinesia, psychosis-like behaviours and parkinsonism in the MPTP-lesioned marmoset.

J Neural Transm (Vienna). 2021-1

[5]
Effect of the glycine transporter 1 inhibitor ALX-5407 on dyskinesia, psychosis-like behaviours and parkinsonism in the MPTP-lesioned marmoset.

Eur J Pharmacol. 2021-11-5

[6]
Effect of the mGlu positive allosteric modulator ADX-88178 on parkinsonism, psychosis-like behaviours and dyskinesia in the MPTP-lesioned marmoset.

Psychopharmacology (Berl). 2023-10

[7]
The mGluR orthosteric agonist LY-404,039 reduces dyskinesia, psychosis-like behaviours and parkinsonism in the MPTP-lesioned marmoset.

Naunyn Schmiedebergs Arch Pharmacol. 2023-10

[8]
Monoamine oxidase A inhibition with moclobemide enhances the anti-parkinsonian effect of L-DOPA in the MPTP-lesioned marmoset.

Naunyn Schmiedebergs Arch Pharmacol. 2020-11

[9]
Combined mGlu orthosteric stimulation and positive allosteric modulation alleviates L-DOPA-induced psychosis-like behaviours and dyskinesia in the parkinsonian marmoset.

J Neural Transm (Vienna). 2020-7

[10]
Combined 5-HT and mGlu modulation for the treatment of dyskinesia and psychosis in Parkinson's disease.

Neuropharmacology. 2021-3-15

引用本文的文献

[1]
Global research trends and hotspots in Parkinson's disease psychosis: a 25-year bibliometric and visual analysis.

Front Aging Neurosci. 2024-11-22

本文引用的文献

[1]
Effect of the mGlu positive allosteric modulator ADX-88178 on parkinsonism, psychosis-like behaviours and dyskinesia in the MPTP-lesioned marmoset.

Psychopharmacology (Berl). 2023-10

[2]
The 5-HT inverse agonist nelotanserin alleviates L-DOPA-induced dyskinesia in the MPTP-lesioned marmoset.

Eur J Neurosci. 2024-3

[3]
Anti-parkinsonian effect of the mGlu positive allosteric modulator LY-487,379 as monotherapy and adjunct to a low L-DOPA dose in the MPTP-lesioned marmoset.

Eur J Pharmacol. 2023-1-15

[4]
Evaluation of the effects of the mGlu antagonist LY341495 on dyskinesia and psychosis-like behaviours in the MPTP-lesioned marmoset.

Pharmacol Rep. 2022-8

[5]
Further characterisation of psychosis-like behaviours induced by L-DOPA in the MPTP-lesioned marmoset.

Naunyn Schmiedebergs Arch Pharmacol. 2021-8

[6]
Combined 5-HT and mGlu modulation for the treatment of dyskinesia and psychosis in Parkinson's disease.

Neuropharmacology. 2021-3-15

[7]
Effect of the mGlu positive allosteric modulator CBiPES on dyskinesia, psychosis-like behaviours and parkinsonism in the MPTP-lesioned marmoset.

J Neural Transm (Vienna). 2021-1

[8]
Selective blockade of the 5-HT receptor acutely alleviates dyskinesia and psychosis in the parkinsonian marmoset.

Neuropharmacology. 2021-1

[9]
The MPTP-lesioned marmoset model of Parkinson's disease: proposed efficacy thresholds that may potentially predict successful clinical trial results.

J Neural Transm (Vienna). 2020-10

[10]
The mGlu antagonist LY-341,495 reverses the anti-dyskinetic and anti-psychotic effects of the mGlu activators LY-487,379 and LY-354,740 in the MPTP-lesioned marmoset.

J Neural Transm (Vienna). 2020-7

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索