更新于：2024-11-01

MAO-B x MAO-A x NMDA receptor

更新于：2024-11-01

基本信息

关联

项与 MAO-B x MAO-A x NMDA receptor 相关的药物

Indantadol Hydrochloride

靶点

MAO-A x MAO-B x NMDA receptor

作用机制

MAO-A抑制剂 [+2]

在研机构-

原研机构

CHIESI Farmaceutici SpA

在研适应症-

非在研适应症

咳嗽 [+5]

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

项与 MAO-B x MAO-A x NMDA receptor 相关的临床试验

NCT01401673 / Terminated临床2期

Phase II Open-label Pilot Study of V3381, a Novel N-Methyl-D-Aspartate Receptor Antagonist, in Chronic Cough Patients Attending a Specialist Clinic

The investigators hypothesise that cough reflex hypersensitivity, demonstrated in chronic cough patients, is due to a phenomenon known as central sensitisation. Central sensitisation is a hyper-excitability of the sensory nerves as they join the central nervous system, and is believed to be mediated by the N-Methyl-D-Aspartate (NMDA) receptor[1-3].

开始日期2009-10-01

申办/合作机构

Vernalis (R&D) Ltd.

[+1]

EUCTR2009-011525-13-GB / Not yet recruitingN/A

Phase II Open-label Pilot Study of V3381, a Novel N-Methyl-D-Aspartate Receptor Antagonist, in Chronic Cough Patients attending a Specialist Clinic - Phase II Open-Label Pilot Study of V3381 in Chronic Cough

开始日期2009-08-28

申办/合作机构

Vernalis (R&D) Ltd.

EUCTR2008-007978-38-GB / Not yet recruitingN/A

A Randomised, Double-Blind, Placebo-Controlled, Multicentre, Parallel Group Study of the Safety, Tolerability and Efficacy of V3381 for Up to 13 Weeks in Patients with Diabetic Peripheral Neuropathic Pain (DPNP) - IN-STEP (Indantadol - Safety Tolerability and Efficacy in Pain)

开始日期2009-02-12

申办/合作机构-

100 项与 MAO-B x MAO-A x NMDA receptor 相关的临床结果

登录后查看更多信息

100 项与 MAO-B x MAO-A x NMDA receptor 相关的转化医学

登录后查看更多信息

0 项与 MAO-B x MAO-A x NMDA receptor 相关的专利（医药）

登录后查看更多信息

项与 MAO-B x MAO-A x NMDA receptor 相关的文献（医药）

2024-05-01·ACS Chemical Neuroscience

Practical Three-Component Regioselective Synthesis of Drug-Like 3-Aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnolines as Potential Non-Covalent Multi-Targeting Inhibitors To Combat Neurodegenerative Diseases

Article

作者: Zeynizadeh, Behzad ; Mousavi, Hossein ; Rimaz, Mehdi

Neurodegenerative diseases (NDs) are one of the prominent health challenges facing contemporary society, and many efforts have been made to overcome and (or) control it. In this research paper, we described a practical one-pot two-step three-component reaction between 3,4-dihydronaphthalen-1(2H)-one (1), aryl(or heteroaryl)glyoxal monohydrates (2a-h), and hydrazine monohydrate (NH₂NH₂•H₂O) for the regioselective preparation of some 3-aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnoline derivatives (3a-h). After synthesis and characterization of the mentioned cinnolines (3a-h), the in silico multi-targeting inhibitory properties of these heterocyclic scaffolds have been investigated upon various Homo sapiens-type enzymes, including hMAO-A, hMAO-B, hAChE, hBChE, hBACE-1, hBACE-2, hNQO-1, hNQO-2, hnNOS, hiNOS, hPARP-1, hPARP-2, hLRRK-2^(G2019S), hGSK-3β, hp38α MAPK, hJNK-3, hOGA, hNMDA receptor, hnSMase-2, hIDO-1, hCOMT, hLIMK-1, hLIMK-2, hRIPK-1, hUCH-L1, hPARK-7, and hDHODH, which have confirmed their functions and roles in the neurodegenerative diseases (NDs), based on molecular docking studies, and the obtained results were compared with a wide range of approved drugs and well-known (with IC₅₀, EC₅₀, etc.) compounds. In addition, in silico ADMET prediction analysis was performed to examine the prospective drug properties of the synthesized heterocyclic compounds (3a-h). The obtained results from the molecular docking studies and ADMET-related data demonstrated that these series of 3-aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnolines (3a-h), especially hit ones, can really be turned into the potent core of new drugs for the treatment of neurodegenerative diseases (NDs), and/or due to the having some reactionable locations, they are able to have further organic reactions (such as cross-coupling reactions), and expansion of these compounds (for example, with using other types of aryl(or heteroaryl)glyoxal monohydrates) makes a new avenue for designing novel and efficient drugs for this purpose.

2022-06-01·Bioorganic Chemistry2区 · 化学

Coumarin derivatives as inhibitors of d-amino acid oxidase and monoamine oxidase

2区 · 化学

Article

作者: Petzer, Anél ; Bester, Elizabeth ; Petzer, Jacobus P

d-Amino acid oxidase (DAAO) oxidises d-amino acids to ultimately produce the corresponding α-keto acids. The DAAO substrate, d-serine, is a co-agonist at NMDA receptors, while NMDA receptor hypo-function has been implicated in the pathophysiology of schizophrenia. Through the modulation of d-serine levels, the inhibition of DAAO represents a strategy to increase NMDA receptor function, and thus a potential treatment for schizophrenia. Literature reports that 3-hydroxycoumarin is a potent inhibitor of DAAO and represents an ideal lead for the development of novel DAAO inhibitors. Based on this, the present study investigated DAAO inhibition by a series of synthetic and commercially available coumarin derivatives. Due to structural similarity to coumarin, a synthetic series of 3,4-dihydroisoquinolin-1(2H)-one derivatives has also been included in this study. The results show that among 37 compound evaluated, four inhibit porcine kidney DAAO with IC₅₀ < 10 µM. The most potent inhibitors are 3,7-dihydroxycoumarin and 6,7-dihydroxycoumarin with an IC₅₀ values of 0.167 and 0.224 µM, respectively. These values are an improvement on that of the reference DAAO inhibitor, 3-methylpyrazole-5-carboxylic acid (IC₅₀ = 1.88 µM). Coumarin compounds are also known to inhibit the monoamine oxidase (MAO) enzymes, which are well established targets for the treatment of depression and Parkinson's disease. As DAAO and MAO are flavoenzymes, off-target inhibition may occur. The series were thus evaluated as potential MAO inhibitors, and a number of high potency inhibitors were identified. Seven compounds inhibit the recombinant human MAOs with IC₅₀ < 0.1 µM, with the most potent MAO-A and MAO-B inhibitors exhibiting IC₅₀ values of 0.033 and 0.012 µM, respectively. This is significantly more potent than the reference inhibitors, curcumin, isatin and toloxatone. This study concludes that active DAAO and MAO inhibitors may serve as novel leads for the design of compounds that may find future application in the treatment of neuropsychiatric (e.g. schizophrenia, depression) and neurodegenerative disorders (e.g. Parkinson's disease).

2013-07-30·Proceedings of the National Academy of Sciences1区 · 综合性期刊

Cognitive abnormalities and hippocampal alterations in monoamine oxidase A and B knockout mice

1区 · 综合性期刊

Article

作者: Thompson, Richard F. ; Scott, Anna L. ; Bortolato, Marco ; Chen, Kevin ; Godar, Sean C. ; Bali, Namrata ; Shih, Jean C. ; Singh, Chanpreet

The monoamine oxidase isoenzymes (MAOs) A and B play important roles in the homeostasis of monoaminergic neurotransmitters. The combined deficiency of MAO A and B results in significantly elevated levels of serotonin (5-hydroxytryptamine), norepinephrine, dopamine, and β-phenylethylamine; in humans and mice, these neurochemical changes are accompanied by neurodevelopmental perturbations as well as autistic-like responses. Ample evidence indicates that normal levels of monoamines in the hippocampus, amygdala, frontal cortex, and cerebellum are required for the integrity of learning and memory. Thus, in the present study, the cognitive status of MAO A/B knockout (KO) mice was examined with a wide array of behavioral tests. In comparison with male wild-type littermates, MAO A/B KO mice exhibited abnormally high and overgeneralized fear conditioning and enhanced eye-blink conditioning. These alterations were accompanied by significant increases in hippocampal long-term potentiation and alterations in the relative expression of NMDA glutamate receptor subunits. Our data suggest that chronic elevations of monoamines, because of the absence of MAO A and MAO B, cause functional alterations that are accompanied with changes in the cellular mechanisms underlying learning and memory. The characteristics exhibited by MAO A/B KO mice highlight the potential of these animals as a useful tool to provide further insight into the molecular bases of disorders associated with abnormal monoaminergic profiles.