更新于：2024-11-01

CHRNA7 x 5-HT3 receptor

更新于：2024-11-01

基本信息

关联

项与 CHRNA7 x 5-HT3 receptor 相关的药物

Facinicline hydrochloride

靶点

5-HT3 receptor x CHRNA7

作用机制

5-HT3 receptor拮抗剂 [+1]

在研机构-

原研机构

F. Hoffmann-La Roche Ltd.

在研适应症-

非在研适应症

阿尔茨海默症 [+2]

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

项与 CHRNA7 x 5-HT3 receptor 相关的临床试验

NCT01196065 / Completed临床1期

A Single Center, Open-label, Fixed Sequence, Two-period Study to Investigate the Effect of Memantine on Pharmacokinetics, Safety and Tolerability of RO5313534 After Single Dose Administration in Healthy Volunteers and the Effect of RO5313534 on Safety and Tolerability of Steady State Memantine

This open-label, fixed sequence, two-period study will assess the effect of memantine on the pharmacokinetics, safety and tolerability of a single oral dose of RO5313534 and the effect of RO5313534 on safety and tolerability of steady-state memantine. Healthy volunteers will receive a single oral dose of RO5313534 on Day 1 of Treatment Period 1 (3 days). After a washout period of 5-21 days, oral memantine will be administered on Days 1-21 of Treatment Period 2 and a single dose of RO5313534 on Day 19. There will be a follow-up of 3-4 weeks after the last dose. Anticipated time on study for each volunteer is up to 14 weeks.

开始日期2010-09-01

申办/合作机构

Hoffmann-La Roche, Inc.

NCT00884507 / Completed临床2期

A Dose-ranging, Randomized, Double-blind , Placebo-controlled Study of the Effect of RO5313534, Used as add-on Therapy to Donepezil, on Cognitive Function in Patients With Mild to Moderate Symptoms of Alzheimer's Disease

This 4 arm study will assess the efficacy and safety of RO5313534 (MEM3454) versus placebo added to donepezil, in patients with mild to moderate Alzheimer's disease. Following a screening period, patients will be randomized to one of 4 treatments (placebo, or RO5313534 1mg, 5mg or 15mg po daily) with background therapy of donepezil (5mg or 10mg).The anticipated time on study treatment is 6 months, and the target sample size is 100-500 individuals.

开始日期2009-05-01

申办/合作机构

Hoffmann-La Roche, Inc.

100 项与 CHRNA7 x 5-HT3 receptor 相关的临床结果

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100 项与 CHRNA7 x 5-HT3 receptor 相关的转化医学

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0 项与 CHRNA7 x 5-HT3 receptor 相关的专利（医药）

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项与 CHRNA7 x 5-HT3 receptor 相关的文献（医药）

2023-05-25·Cellular and molecular life sciences : CMLS

Generation of nanobodies acting as silent and positive allosteric modulators of the α7 nicotinic acetylcholine receptor.

Article

作者: Maskos, Uwe ; Lafaye, Pierre ; Corringer, Pierre-Jean ; Prevost, Marie S ; Pons, Stéphanie ; Barilone, Nathalie ; Aymé, Gabriel ; Baachaoui, Rayen ; Li, Qimeng ; Nemecz, Ákos ; Dejean de la Bâtie, Gabrielle

The α7 nicotinic acetylcholine receptor (nAChR), a potential drug target for treating cognitive disorders, mediates communication between neuronal and non-neuronal cells. Although many competitive antagonists, agonists, and partial-agonists have been found and synthesized, they have not led to effective therapeutic treatments. In this context, small molecules acting as positive allosteric modulators binding outside the orthosteric, acetylcholine, site have attracted considerable interest. Two single-domain antibody fragments, C4 and E3, against the extracellular domain of the human α7-nAChR were generated through alpaca immunization with cells expressing a human α7-nAChR/mouse 5-HT₃A chimera, and are herein described. They bind to the α7-nAChR but not to the other major nAChR subtypes, α4β2 and α3β4. E3 acts as a slowly associating positive allosteric modulator, strongly potentiating the acetylcholine-elicited currents, while not precluding the desensitization of the receptor. An E3-E3 bivalent construct shows similar potentiating properties but displays very slow dissociation kinetics conferring quasi-irreversible properties. Whereas, C4 does not alter the receptor function, but fully inhibits the E3-evoked potentiation, showing it is a silent allosteric modulator competing with E3 binding. Both nanobodies do not compete with α-bungarotoxin, localizing at an allosteric extracellular binding site away from the orthosteric site. The functional differences of each nanobody, as well as the alteration of functional properties through nanobody modifications indicate the importance of this extracellular site. The nanobodies will be useful for pharmacological and structural investigations; moreover, they, along with the extracellular site, have a direct potential for clinical applications.

2023-04-21·Medicine

Exploring the molecular mechanism of Nux Vomica in treating ischemic stroke using network pharmacology and molecular docking methods

Article

作者: Fan, Xiaohua ; Zhang, Chengdong ; Gai, Jialin ; Lei, Junfang ; Tang, Jiqin

Background:Nux Vomica (NV) has the effects of dredging collaterals, relieving pain, dispersing knots, and detumescence, and has a verified effect in treating ischemic stroke (IS), but its molecular mechanism for treating IS remains unclear. In this study, network pharmacology and molecular docking methods were adopted to explore the pharmacological mechanism of NV in treating IS.Methods:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the HERB database were searched to screen the active components and targets of NV. IS disease targets were retrieved from the DisGeNET, DrugBank, GeneCards, and Therapeutic Target Database. Venn diagram and intersection targets were obtained from the Venny website. Subsequently, the STRING database was employed to analyze the interrelationship of the intersection targets. Metascape database was used for Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of intersection targets. Furthermore, Cytoscape was employed to plot a drug-component-target network, and other networks, and molecular docking method was adopted to predict the effective components and targets of NV for treating IS.Results:A total of 14 active compounds and 59 targets of NV were screened, of which 35 targets were related to IS. Stigmasterol, brucine, isobrucine, isostrychnine N-oxide (I), (S)-stylopine, icaride A, and (2R)-5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one were the main active ingredients, and SLC6A4, NR3C1, SLC6A3, HTR3A, CHRNA7, MAOA, PTGS2, ESR1, catalase (CAT), ADRB2, and AR were the core targets. Molecular docking shows that these compounds bind well to the core targets. In addition, the treatment of IS by NV may mainly involve salivary secretion, serotonergic synapse, calcium signaling pathway, cGMP-PKG signaling pathway, and neuroactive ligand-receptor interaction.Conclusions:This study revealed that NV exerts its therapeutic effect on IS through multi-component, multi-target, and multi-pathway, which provides a basis for clinical treatment of IS.

2021-05-01·Progress in Neurobiology1区 · 医学

NMDA receptor-independent LTP in mammalian nervous system

1区 · 医学

Review

作者: Alkadhi, Karim A

Long-term potentiation (LTP) of synaptic transmission is a form of activity-dependent synaptic plasticity that exists at most synapses in the nervous system. In the central nervous system (CNS), LTP has been recorded at numerous synapses and is a prime candidate mechanism associating activity-dependent plasticity with learning and memory. LTP involves long-lasting increase in synaptic strength with various underlying mechanisms. In the CNS, the predominant type of LTP is believed to be dependent on activation of the ionotropic glutamate N-methyl-D-aspartate receptor (NMDAR), which is highly calcium-permeable. However, various forms of NMDAR-independent LTP have been identified in diverse areas of the nervous system. The NMDAR-independent LTP may require activation of glutamate metabotropic receptors (mGluR) or ionotropic receptors other than NMDAR such as nicotinic acetylcholine receptor (α7-nAChR), serotonin 5-HT3 receptor or calcium-permeable AMPA receptor (CP-AMPAR). In this review, NMDAR-independent LTP of various areas of the central and peripheral nervous systems are discussed.