2,125 results match your criteria Toxicity Monoamine Oxidase Inhibitor


Oligodendrocyte death and myelin loss in the cuprizone model: an updated overview of the intrinsic and extrinsic causes of cuprizone demyelination.

Mol Neurodegener 2022 May 7;17(1):34. Epub 2022 May 7.

Faculty of Medicine & Dentistry, Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Canada.

Background: The dietary consumption of cuprizone - a copper chelator - has long been known to induce demyelination of specific brain structures and is widely used as model of multiple sclerosis. Despite the extensive use of cuprizone, the mechanism by which it induces demyelination are still unknown. With this review we provide an updated understanding of this model, by showcasing two distinct yet overlapping modes of action for cuprizone-induced demyelination; 1) damage originating from within the oligodendrocyte, caused by mitochondrial dysfunction or reduced myelin protein synthesis. Read More

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Development of novel monoamine oxidase B (MAO-B) inhibitors by combined application of docking-based alignment, 3D-QSAR, ADMET prediction, molecular dynamics simulation, and MM_GBSA binding free energy.

J Biomol Struct Dyn 2022 May 5:1-14. Epub 2022 May 5.

LPME Laboratory, Faculty of Science and Technology, Sidi Mohamed Ben Abdellah University, Fez, Morocco.

Unsaturated ketone derivatives are known as inhibitors of monoamine oxidase B (MAO-B), a potential drug target of Parkinson's disease. Here, docking-based alignment, 3 D-QSAR (three-dimensional quantitative structure-activity relationship) studies, ADMET (absorption, distribution, metabolism, excretion, and toxicity) prediction, molecular dynamics (MD) simulation, and MM_GBSA binding free energy were performed on a novel series of MAO-B inhibitors. The objective is to predict new MAO-B inhibitors with high potency activity. Read More

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Quinazolinone-based benzenesulfonamides with low toxicity and high affinity as monoamine oxidase-A inhibitors: Synthesis, biological evaluation and induced-fit docking studies.

Bioorg Chem 2022 Apr 21;124:105822. Epub 2022 Apr 21.

Van Yüzüncü Yıl University, Faculty of Veterinary Medicine, Department of Pharmacology and Toxicology, Van, Turkey.

The research in selective monoamine oxidases (MAO-A and MAO-B) inhibitors has been increased due to their therapeutic value for neurodegenerative diseases. In this study, 4-((2-(aryl)-4-oxoquinazolin-3(4H)-yl)amino)benzenesulfonamides were synthesized and their MAOs inhibition potentials were investigated applying in vitro fluorometric technique. The most potent compounds 7 and 8 against MAO-A had IC values of 0. Read More

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TRPV2: A Key Player in Myelination Disorders of the Central Nervous System.

Int J Mol Sci 2022 Mar 25;23(7). Epub 2022 Mar 25.

Biophysics Unit, Department of Biochemistry and Molecular Biology, School of Medicine, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Catalonia, Spain.

Transient potential receptor vanilloid 2 (TRPV2) is widely expressed through the nervous system and specifically found in neuronal subpopulations and some glial cells. TRPV2 is known to be sensitized by methionine oxidation, which results from inflammation. Here we aim to characterize the expression and regulation of TRPV2 in myelination pathologies, such as hypomyelination and demyelination. Read More

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Phenytoin promotes the proliferation of oligodendrocytes and enhances the expression of myelin basic protein in the corpus callosum of mice demyelinated by cuprizone.

Exp Brain Res 2022 May 1;240(5):1617-1627. Epub 2022 Apr 1.

Laboratorio de Neurociencias, Facultad de Psicologia, Universidad de Colima, Av. Universidad 333, 28040, Colima, COL, Mexico.

Oligodendrocyte loss and myelin sheet destruction are crucial characteristics of demyelinating diseases. Phenytoin promotes the proliferation of endogenous neural precursor cells in the ventricular-subventricular zone in the postnatal brain that help restore the oligodendroglial population. This study aimed to evaluate whether phenytoin promotes myelin recovery of the corpus callosum of demyelinated adult mice. Read More

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Design, Synthesis, and Bioevaluation of Indole Core Containing 2-Arylidine Derivatives of Thiazolopyrimidine as Multitarget Inhibitors of Cholinesterases and Monoamine Oxidase A/B for the Treatment of Alzheimer Disease.

ACS Omega 2022 Mar 10;7(11):9369-9379. Epub 2022 Mar 10.

Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, Pakistan.

In continuation of our previous study to identify multitarget inhibitors of cholinesterases (ChEs) and monoamine oxidase (MAOs) isoforms, we synthesized and evaluated 2-arylidine derivatives of thiazolopyrimidine for the treatment of Alzheimer disease. Three series of compounds with different linker size and target-anchoring functional groups were synthesized. Compounds - showed excellent to good AChE and BChE inhibition potential at nanomolar to low micromolar concentration. Read More

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Antidepressant activity of phytochemicals of Mangifera indica seeds assisted by integrated computational analysis.

Metab Brain Dis 2022 Mar 28. Epub 2022 Mar 28.

Department of Biology, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia.

Mangifera indica L., also known as mango, is a tropical fruit that belongs to the Anacardiaceae family and is prized for its juiciness, unique flavour, and worldwide popularity. The current study aimed to probe into antidepressant power (ADP) of MIS in animals and confirmation of ADP with in silico induced-fit molecular docking. Read More

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Synthesis of harmine-nitric oxide donor derivatives as potential antitumor agents.

Bioorg Med Chem Lett 2022 06 24;65:128698. Epub 2022 Mar 24.

College of Pharmacy, Xinjiang Medical University, Urumqi 830000, China. Electronic address:

To further improve the anti-tumor activity of Harmine (HM), we took the hybridization approach and synthesized harmine derivatives-furoxan hybrids containing nitric oxide (NO) releasing parts by connecting NO donors with anti-tumor active fragments to harmine. Then, the synthesized compounds were evaluated for their in vitro cytotoxicity against five human cancer cell lines. Among them, compound 10 was found to have the strongest antiproliferative activity against HepG2 (IC = 1. Read More

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Ceramide kinase knockout ameliorates multiple sclerosis-like behaviors and demyelination in cuprizone-treated mice.

Life Sci 2022 May 2;296:120446. Epub 2022 Mar 2.

Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.

Changes in sphingolipid metabolism regulate and/or alter many cellular functions in the brain. Ceramide, a central molecule of sphingolipid metabolism, is phosphorylated to ceramide-1-phosphate (C1P) by ceramide kinase (CerK). CerK and C1P were reported to regulate many cellular responses, but their roles in immune-related diseases in vivo have not been well elucidated. Read More

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Novel Series of Dual NRF2 Inducers and Selective MAO-B Inhibitors for the Treatment of Parkinson's Disease.

Antioxidants (Basel) 2022 Jan 27;11(2). Epub 2022 Jan 27.

Instituto de Química Médica, Consejo Superior de Investigaciones Científicas (IQM-CSIC), 28006 Madrid, Spain.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease. It is characterized by a complex network of physiopathological events where oxidative stress plays a central role among other factors such as neuroinflammation and protein homeostasis. Nuclear factor-erythroid 2 p45-related factor 2 (NRF2) has a multitarget profile itself as it controls a plethora of cellular processes involved in the progression of the disease. Read More

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January 2022

Carbon tetrachloride induced mitochondrial division, respiratory chain damage, abnormal intracellular [H] and apoptosis are due to the activation of 5-HT degradation system in hepatocytes.

Toxicol Appl Pharmacol 2022 03 21;439:115929. Epub 2022 Feb 21.

Department of Physiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address:

Previously we found that acute liver injury (ALI) with inflammation caused by carbon tetrachloride (CCl) was associated with the activation of the 5-HT degradation system (5DS), which includes monoamine oxidase A (MAO-A), the 5-HT receptor, and 5-HT synthases in hepatocytes. This study aimed to determine the role of 5DS in mitochondrial damage and apoptosis. In hepatocyte LO2 cells, CCl activated 5-HT receptor at the gene level, and then 5-HT receptor mediated the expression of 5-HT synthase and MAO-A at the gene level. Read More

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Phenylalanine-Based AMPA Receptor Antagonist as the Anticonvulsant Agent with Neuroprotective Activity-In Vitro and In Vivo Studies.

Molecules 2022 Jan 27;27(3). Epub 2022 Jan 27.

Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, 9 Medyczna St., 30-688 Krakow, Poland.

Trying to meet the multitarget-directed ligands strategy, a series of previously described aryl-substituted phenylalanine derivatives, reported as competitive antagonists of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, were screened in vitro for their free-radical scavenging and antioxidant capacity in two different assays: ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity fluorescent (ORAC-FL) assays. The most active antioxidants and were further examined to evaluate their neuroprotective properties in vitro. In this study, compound showed a significant neuroprotective effect against the neurotoxin 6-hydroxydopamine in neuroblastoma SH-SY5Y and IMR-32 cell lines. Read More

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January 2022

Ultrastructural studies of photoreceptor cell degeneration with organophosphate and its regeneration in Cyprinus carpio communis L.

Micron 2022 04 3;155:103225. Epub 2022 Feb 3.

Department of Zoology, Panjab University, Chandigarh 160014, India.

Organophosphates are highly neurotoxic to aquatic fauna if they enter the water bodies as runoff, thus affecting the nervous system of the fishes. The present study was undertaken to investigate the vision changes, especially on the photoreceptor layer of the retina, of Cyprinus carpio communis L. when exposed to monocrotophos, an organophosphate. Read More

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Polyvinylchloride and polypropylene as adsorbents of the pesticide monocrotophos enhance oxidative stress in Eudrillus eugeniae (Kinberg).

Chemosphere 2022 May 1;295:133837. Epub 2022 Feb 1.

Department of Zoology, Odisha University of Agriculture and Technology, College of Basic Science and Humanities, Bhubaneswar, 751003, India.

The use of plastics has increased significantly with consequent rise in the generation of wastes. Microplastics (MPs) with particle size <5 mm are produced in natural terrestrial habitats by weathering of the discarded plastic debris and therefore are likely to impact soil biota. Earthworms are the dominant soil fauna which play vital role in soil formation and decomposition of organics. Read More

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Computational studies on the cholinesterase, beta-secretase 1 (BACE1) and monoamine oxidase (MAO) inhibitory activities of endophytes-derived compounds: towards discovery of novel neurotherapeutics.

J Biomol Struct Dyn 2022 Feb 4:1-15. Epub 2022 Feb 4.

Biotechnology, Computational Biochemistry and Phytomedicine Research Group, Department of Biochemistry, Faculty of Basic Medical Sciences, University of Medical Sciences, Ondo City, Ondo State, Nigeria.

Cholinesterases, beta-secretase 1 (BACE1) and monoamine oxidase (MAO) are significant in the etiology of neurodegenerative diseases. Inhibition of these enzymes is therefore a major strategy for the development of neurotherapeutics. Even though, this strategy has birthed some approved synthetic drugs, they are characterized by adverse effects. Read More

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February 2022

The roles of microglia and astrocytes in phagocytosis and myelination: Insights from the cuprizone model of multiple sclerosis.

Glia 2022 Jul 2;70(7):1215-1250. Epub 2022 Feb 2.

School of Science, Western Sydney University, Penrith, Australia.

In human demyelinating diseases such as multiple sclerosis (MS), an imbalance between demyelination and remyelination can trigger progressive degenerative processes. The clearance of myelin debris (phagocytosis) from the site of demyelination by microglia is critically important to achieve adequate remyelination and to slow the progression of the disease. However, how microglia phagocytose the myelin debris, and why clearance is impaired in MS, is not fully known; likewise, the role of the microglia in remyelination remains unclear. Read More

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(R)-ketamine ameliorates demyelination and facilitates remyelination in cuprizone-treated mice: A role of gut-microbiota-brain axis.

Neurobiol Dis 2022 04 25;165:105635. Epub 2022 Jan 25.

Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan. Electronic address:

Multiple sclerosis (MS) is the most common demyelinating disease that attacks the central nervous system. We recently reported that the new antidepressant (R)-ketamine could ameliorate the disease progression in experimental autoimmune encephalomyelitis model of MS. Cuprizone (CPZ) has been used to produce demyelination which resembles demyelination in MS patients. Read More

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Comparison of the Effects of Cuprizone on Demyelination in the Corpus Callosum and Hippocampal Progenitors in Young Adult and Aged Mice.

Neurochem Res 2022 Apr 21;47(4):1073-1082. Epub 2022 Jan 21.

Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul, 08826, South Korea.

Cuprizone is commonly used to induce neuronal demyelination in mice. In the present study, we compared the cuprizone-induced demyelination in the corpus callosum and investigated the effects of cuprizone on proliferating cells and neuroblasts in the dentate gyrus of young adult and aged mice. 5-week- and 23-month-old mice were fed a normal diet or a 0. Read More

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Paeonol Ameliorates Cuprizone-Induced Hippocampal Demyelination and Cognitive Deficits through Inhibition of Oxidative and Inflammatory Events.

J Mol Neurosci 2022 Apr 10;72(4):748-758. Epub 2022 Jan 10.

Neurophysiology Research Center, Shahed University, Tehran, Iran.

Multiple sclerosis (MS) is a chronic and inflammatory disorder of the central nervous system with autoimmune nature that is typified by varying degrees of demyelination and axonal damage. Paeonol is an active ingredient in some medicinal plants with anti-inflammatory and neuroprotective property. This study was conducted to reveal whether paeonol can alleviate hippocampal demyelination and cognitive deficits in cuprizone-induced murine model of demyelination as a model of MS. Read More

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Selegiline Protects Against Lipopolysaccharide (LPS)-Induced Impairment of the Blood-Brain Barrier Through Regulating the NF-κB/MLCK/p-MLC Signaling Pathway.

Neurotox Res 2022 Feb 4;40(1):267-275. Epub 2022 Jan 4.

Department of Emergency Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No.110 Ganhe Road, Hongkou District, Shanghai, 200437, China.

Disruption of the blood-brain barrier (BBB) is an important hallmark of sepsis-associated encephalopathy (SAE). Selegiline, a selective and irreversible inhibitor of monoamine oxidase type B, has been applied for the treatment of nervous disorders. In this study, we aimed to investigate whether selegiline has a protective capacity in the impairment of the BBB in both in vivo and in vitro experiments. Read More

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February 2022

Colony-stimulating factor-1 receptor inhibition attenuates microgliosis and myelin loss but exacerbates neurodegeneration in the chronic cuprizone model.

J Neurochem 2022 03 9;160(6):643-661. Epub 2022 Jan 9.

Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Cátedra de Química Biológica Patológica, Universidad de Buenos Aires, Buenos Aires, Argentina.

Multiple sclerosis (MS), especially in its progressive phase, involves early axonal and neuronal damage resulting from a combination of inflammatory mediators, demyelination, and loss of trophic support. During progressive disease stages, a microenvironment is created within the central nervous system (CNS) favoring the arrival and retention of inflammatory cells. Active demyelination and neurodegeneration have also been linked to microglia (MG) and astrocyte (AST)-activation in early lesions. Read More

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C1q inhibits differentiation of oligodendrocyte progenitor cells via Wnt/β-catenin signaling activation in a cuprizone-induced mouse model of multiple sclerosis.

Exp Neurol 2022 02 10;348:113947. Epub 2021 Dec 10.

Department of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou 221009, PR China. Electronic address:

Multiple sclerosis (MS) is a chronic central nervous system demyelinating disease of autoimmune originate. Complement C1q, a complex glycoprotein, mediates a variety of immunoregulatory functions considered important in the prevention of autoimmunity. Although we found that the increased serum C1q level was highly associated with the Fazekas scores and T2 lesion volume of MS patients, the effect and mechanism of C1q on demyelination remains unclear. Read More

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February 2022

Differential Role of p53 in Oligodendrocyte Survival in Response to Various Stresses: Experimental Autoimmune Encephalomyelitis, Cuprizone Intoxication or White Matter Stroke.

Int J Mol Sci 2021 Nov 26;22(23). Epub 2021 Nov 26.

Department of Molecular Genetics and Biochemistry, College of Medicine, University of Cincinnati, Cincinnati, OH 45214, USA.

Promoting oligodendrocyte viability has been proposed as a therapeutic strategy for alleviating many neuronal diseases, such as multiple sclerosis and stroke. However, molecular pathways critical for oligodendrocyte survival under various stresses are still not well known. p53 is a strong tumor suppressor and regulates cell cycle, DNA repair and cell death. Read More

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November 2021

Isoliquiritigenin, a potent human monoamine oxidase inhibitor, modulates dopamine D, D, and vasopressin V receptors.

Sci Rep 2021 12 7;11(1):23528. Epub 2021 Dec 7.

Department of Food and Life Science, Pukyong National University, Busan, 48513, Republic of Korea.

Isoliquiritigenin (= 4,2',4'-Trihydroxychalcone) (ILG) is a major constituent of the Glycyrrhizae Rhizoma that has significant neuroprotective functions. In the present study, we re-examined the potential of ILG to inhibit human monoamine oxidase (hMAO) in vitro and established its mechanism of inhibition through a kinetics study and molecular docking examination. ILG showed competitive inhibition of hMAO-A and mixed inhibition of hMAO-B with IC values of 0. Read More

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December 2021

Anxiolytic, antidepressant and inhibitory effect on MAO isoenzymes by Bougainvillea glabra flower extract in rats.

Pak J Pharm Sci 2021 Sep;34(5(Supplementary)):1963-1968

Faculty of Pharmacy, Hamdard University, Karachi, Pakistan.

Main aim of current study was to determine the anxiolytic and antidepressant potential of Bougainvillea glabra Extract (BVE). The effects were investigated by using Open-Field-Test (OFT), Light-and-Dark Model (LD), Hole-Board (HB) and Forced-Swimming-Test (FST). Different doses for BVE were given to Wistar-Rats and compared with Control and Diazepam. Read More

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September 2021

Replacement of Chalcone-Ethers with Chalcone-Thioethers as Potent and Highly Selective Monoamine Oxidase-B Inhibitors and Their Protein-Ligand Interactions.

Pharmaceuticals (Basel) 2021 Nov 11;14(11). Epub 2021 Nov 11.

Department of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Korea.

To develop new potent and highly selective MAO-B inhibitors from chalcone-thioethers, eleven chalcones-thioethers were synthesized and their monoamine oxidase (MAO) inhibition, kinetics, reversibility, and cytotoxicity of lead compounds were analyzed. Molecular dynamics were carried out to investigate the interactions. Compound showed potent inhibitory activity against MAO-B, with an IC value of 0. Read More

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November 2021

The serotonin toxidrome: shortfalls of current diagnostic criteria for related syndromes.

Clin Toxicol (Phila) 2022 Feb 22;60(2):143-158. Epub 2021 Nov 22.

NSW Poisons Information Centre, The Children's Hospital at Westmead, Westmead, Australia.

Introduction: Serotonin syndrome (toxicity) describes adverse drug effects from toxic amounts of intra-synaptic central nervous system serotonin. A wide range of drugs have been implicated to cause serotonin toxicity, not all justifiably. The plausible agents all have a final common pathway resulting in a substantial increase in central nervous system serotonergic neurotransmission. Read More

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February 2022

Dual monoamine oxidase B and acetylcholine esterase inhibitors for treating movement and cognition deficits in a model of Parkinson's disease.

Med Chem Res 2021 May 9;30(5):1166-1174. Epub 2021 Apr 9.

Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, WV, USA.

Parkinson's disease (PD) is an age-associated neurodegenerative movement disorder that leads to loss of dopaminergic neurons and motor deficits. Approaches to neuroprotection and symptom management in PD include use of monoamine oxidase B (MAO-B) inhibitors. Many patients with PD also exhibit memory loss in the later stages of disease progression, which is treated with acetylcholine esterase (AChE) inhibitors. Read More

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Halogenated Coumarin-Chalcones as Multifunctional Monoamine Oxidase-B and Butyrylcholinesterase Inhibitors.

ACS Omega 2021 Oct 12;6(42):28182-28193. Epub 2021 Oct 12.

Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi 682 041, India.

A series of halogenated coumarin-chalcones were synthesized, characterized, and their inhibitory activities against monoamine oxidases (MAOs), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein cleaving enzyme 1 (BACE-1) were evaluated. Compound most potently inhibited MAO-B with an IC value of 0.51 μM, followed by (IC = 0. Read More

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October 2021

Fluoxetine and sertraline based multitarget inhibitors of cholinesterases and monoamine oxidase-A/B for the treatment of Alzheimer's disease: Synthesis, pharmacology and molecular modeling studies.

Int J Biol Macromol 2021 Dec 20;193(Pt A):19-26. Epub 2021 Oct 20.

Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, 22060 Abbottabad, Pakistan. Electronic address:

For the potential therapy of Alzheimer's disease (AD), cholinesterases (ChE) and monoamine oxidase (MAO) are key enzymes that regulate the level of acetylcholinesterase (AChE)/butyrylcholinesterase (BChE) and monoamines. The aim of current research is the synthesis of multi-target compounds that can concomitantly inhibit ChEs and MAO. A series of fluoxetine and sertraline hybrids was designed and evaluated as multi-target inhibitors of ChEs and hMAO. Read More

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December 2021