1,880 results match your criteria Toxicity Monoamine Oxidase Inhibitor


Effects of Epacadostat on Brain Extracellular Fluid Concentrations of Serotonin -- An Intracerebral Microdialysis Study in Sprague-Dawley Rats.

Drug Metab Dispos 2019 Apr 22. Epub 2019 Apr 22.

Incyte.

Epacadostat (EPAC) is an indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor that has been examined in multiple clinical trials. The substrate for IDO1 is tryptophan and there is a theoretical concern that inhibition of IDO1 may increase the concentrations of tryptophan and subsequently serotonin, potentially leading to serotonin syndrome (SS). The objective of this study was to evaluate the effect of EPAC, either alone or with linezolid, a monoamine oxidase inhibitor (MAOI), on brain ECF concentrations of serotonin in rats, using microdialysis. Read More

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http://dx.doi.org/10.1124/dmd.118.084053DOI Listing

Attenuation of the effects of oxidative stress by the MAO-inhibiting antidepressant and carbonyl scavenger phenelzine.

Chem Biol Interact 2019 May 8;304:139-147. Epub 2019 Mar 8.

Department of Psychiatry (Neurochemical Research Unit), University of Alberta, Edmonton, Canada; Department of Medicine (Neurology), University of Alberta, Edmonton, Canada. Electronic address:

Phenelzine (β-phenylethylhydrazine) is a monoamine oxidase (MAO)-inhibiting antidepressant with anxiolytic properties. It possesses a number of important pharmacological properties which may alter the effects of oxidative stress. After conducting a comprehensive literature search, the authors of this review paper aim to provide an overview and discussion of the mechanisms by which phenelzine may attenuate oxidative stress. Read More

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http://dx.doi.org/10.1016/j.cbi.2019.03.003DOI Listing
May 2019
3 Reads

Syrian rue seeds interacted with acacia tree bark in an herbal stew resulted in N,N-dimethyltryptamine poisoning.

Clin Toxicol (Phila) 2019 Mar 4:1-3. Epub 2019 Mar 4.

d Department of Emergency Medicine , Chang Gung Memorial Hospital , Keelung , Taiwan.

Introduction: Illicit substance use is an increasing problem all over the world, especially in adolescents and young adults. It is a challenge to make a definitive diagnosis of a specific substance in a poisoning case without toxicology laboratory confirmation. We confirmed the presence of N,N-dimethyltryptamine (DMT) by liquid chromatograph tandem mass spectrometer (LC/MS/MS) in biologic samples from two patients who presented with signs and symptoms consistent with sympathomimetic toxicity following the consumption of an herbal stew. Read More

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http://dx.doi.org/10.1080/15563650.2019.1576877DOI Listing
March 2019
5 Reads

Renalase attenuates mitochondrial fission in cisplatin-induced acute kidney injury via modulating sirtuin-3.

Life Sci 2019 Apr 21;222:78-87. Epub 2019 Feb 21.

Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China. Electronic address:

Aims: Acute kidney injury (AKI) can limit the clinical use of cisplatin in cancer treatment. The drivers of cisplatin-induced AKI include oxidative stress, mitochondrial dysfunction and apoptosis. Previous studies showed renalase protected cultured human renal proximal tubular cell (HK-2) against cisplatin induced necrosis, and renalase-knockout mice subjected to cisplatin showed exacerbated kidney injury. Read More

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http://dx.doi.org/10.1016/j.lfs.2019.02.042DOI Listing
April 2019
2 Reads

Inhibitor structure-guided design and synthesis of near-infrared fluorescent probes for monoamine oxidase A (MAO-A) and its application in living cells and in vivo.

Chem Commun (Camb) 2019 Feb;55(17):2477-2480

State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, P. R. China.

A series of near-infrared fluorescent probes based on inhibitor (clorgyline) structure-guided design were synthesized for the specific detection of MAO-A in cells and in vivo. Moreover, we have successfully used the high specificity of one of the probes to visualize MAO-A activity in zebrafish and tumor tissue for the first time. Read More

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http://dx.doi.org/10.1039/c8cc10084eDOI Listing
February 2019
5 Reads
6.834 Impact Factor

Adjuvant potential of selegiline in treating acute toxicity of aluminium phosphide in rats.

Basic Clin Pharmacol Toxicol 2019 Feb 3. Epub 2019 Feb 3.

Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Aluminium phosphide (AlP) is a highly toxic substance with a high mortality rate and no effective antidote. Once exposed to the moisture and acidic conditions of the stomach, AlP releases toxic phosphine (PH ) gas, which results in severe toxicity in poisoned subjects. Selegiline is a monoamine oxidase inhibitor with antioxidant and anti-apoptotic properties, which is mostly prescribed for the treatment of mood disorders and Parkinson's disease. Read More

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http://dx.doi.org/10.1111/bcpt.13207DOI Listing
February 2019
2 Reads

Hazardous ecotoxicological impact of two commonly used nitrofuran-derived antibacterial drugs: Furazolidone and nitrofurantoin.

Chemosphere 2019 May 26;222:381-390. Epub 2019 Jan 26.

Faculty of Mathematics and Natural Science, Jan Długosz University in Częstochowa, 13/15 Armii Krajowej Av., 42-200 Częstochowa, Poland. Electronic address:

This paper discusses the impact of two nitrofuran-derived drugs, namely furazolidone and nitrofurantoin on growth of oat and common radish as well as their impact on bacteria Allivibrio fischeri and crustaceans Heterocypris incongruens. Results indicated that both compounds were highly phytotoxic for radish (R. sativus) being simultaneously nearly not harmful for oat (A. Read More

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http://dx.doi.org/10.1016/j.chemosphere.2019.01.144DOI Listing
May 2019
2 Reads
3.340 Impact Factor

Monoamine oxidase-B inhibitors as potential neurotherapeutic agents: An overview and update.

Med Res Rev 2019 Jan 2. Epub 2019 Jan 2.

Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology, Banaras Hindu University, Varanasi, India.

Monoamine oxidase (MAO) inhibitors have made significant contributions and remain an indispensable approach of molecular and mechanistic diversity for the discovery of antineurodegenerative drugs. However, their usage has been hampered by nonselective and/or irreversible action which resulted in drawbacks like liver toxicity, cheese effect, and so forth. Hence, the search for selective MAO inhibitors (MAOIs) has become a substantial focus in current drug discovery. Read More

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http://dx.doi.org/10.1002/med.21561DOI Listing
January 2019
2 Reads

Arecoline attenuates memory impairment and demyelination in a cuprizone-induced mouse model of schizophrenia.

Neuroreport 2019 01;30(2):134-138

Xiamen Xian Yue Hospital, Xiamen, Fujian.

Cerebral demyelination is possibly one of the main pathological factors involved in the development of schizophrenia. Our previous studies have showed that Areca catechu nut extract could ameliorate cognitive decline by facilitating myelination processes in the frontal cortex in a cuprizone (CPZ)-induced mouse model of schizophrenia. The aim of the present study was to evaluate the effects of arecoline, one of the alkaloids in A. Read More

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http://Insights.ovid.com/crossref?an=00001756-201901020-0001
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http://dx.doi.org/10.1097/WNR.0000000000001172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326265PMC
January 2019
2 Reads
1.644 Impact Factor

Mitochondrial Impairment in Oligodendroglial Cells Induces Cytokine Expression and Signaling.

J Mol Neurosci 2019 Feb 13;67(2):265-275. Epub 2018 Dec 13.

Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, Wendlingweg 2, 52074, Aachen, Germany.

Widespread inflammatory lesions within the central nervous system grey and white matter are major hallmarks of multiple sclerosis. The development of full-blown demyelinating multiple sclerosis lesions might be preceded by preactive lesions which are characterized by focal microglia activation in close spatial relation to apoptotic oligodendrocytes. In this study, we investigated the expression of signaling molecules of oligodendrocytes that might be involved in initial microglia activation during preactive lesion formation. Read More

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http://dx.doi.org/10.1007/s12031-018-1236-6DOI Listing
February 2019
1 Read

Design, Synthesis, and Evaluation of Novel Ferulic Acid Derivatives as Multi-Target-Directed Ligands for the Treatment of Alzheimer's Disease.

ACS Chem Neurosci 2019 Feb 4;10(2):1008-1024. Epub 2019 Jan 4.

College of Chemistry and Pharmaceutical Engineering , Nanyang Normal University , Nanyang , 473061 , China.

A novel series of ferulic acid derivatives was designed and synthesized on the basis of the multi-target-directed ligands strategy for the treatment of Alzheimer's disease (AD). In vitro results revealed that all the target compounds were highly effective and selective butyrylcholinesterase (BuChE) inhibitors. In particular, compound TM-10 showed the best BuChE inhibitory activity, with IC = 8. Read More

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http://dx.doi.org/10.1021/acschemneuro.8b00530DOI Listing
February 2019
11 Reads

Synthesis and evaluation of isoprenylation-resveratrol dimer derivatives against Alzheimer's disease.

Eur J Med Chem 2019 Feb 26;163:307-319. Epub 2018 Nov 26.

Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. Electronic address:

A series of resveratrol dimer derivatives against Alzheimer's disease (AD) was obtained by structural modification and transformation using resveratrol as substrate. Biological analysis revealed that these derivatives had moderate inhibitory activity against human monoamine oxidase B (hMAO-B). In particular, 3 and 7 showed the better inhibitory activity for hMAO-B (IC = 3. Read More

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http://dx.doi.org/10.1016/j.ejmech.2018.11.040DOI Listing
February 2019
2 Reads
3.447 Impact Factor

Peroxisome proliferator-activated receptor-γ activation attenuates harmaline-induced cognitive impairments in rats.

J Clin Neurosci 2019 Jan 22;59:276-283. Epub 2018 Nov 22.

Intracellular Recording Lab, Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman.

Cognitive and motor disturbances are serious concerns of the tremors induced by motor disorders. Despite the lack of effective clinical treatment, some potential therapeutic agents have been used to alleviate the cognitive symptoms in the animal models of tremor. Recent studies have shown that PPAR-γ agonists have neuroprotective effects. Read More

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http://dx.doi.org/10.1016/j.jocn.2018.11.004DOI Listing
January 2019
3 Reads
1.318 Impact Factor

Demystifying serotonin syndrome (or ).

Can Fam Physician 2018 Oct;64(10):720-727

Assistant Professor and Acting Director of the Doctor of Pharmacy program at the Leslie Dan Faculty of Pharmacy at the University of Toronto in Ontario, an advanced practice hospital pharmacist at the Centre for Addiction and Mental Health in Toronto, a doctoral candidate in the School of Health Professions Education at Maastricht University in the Netherlands, and a research fellow at the Wilson Centre in Toronto.

Objective: To review the symptoms of serotonin toxicity (commonly referred to as ) and the causative drugs and their mechanisms of action, and to equip primary care providers with practical strategies to prevent and identify serotonin toxicity.

Quality Of Evidence: PubMed and Google Scholar were searched for relevant articles on serotonin toxicity, the causes, and the differential diagnosis using search terms related to serotonin toxicity (), causes (individual names of drug classes, individual drug names), and diagnosis (). Experts in psychiatric medicine, psychiatric pharmacy, clinical pharmacology, and medical toxicology were consulted. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6184959PMC
October 2018
9 Reads

Low-level laser therapy modulates demyelination in mice.

J Photochem Photobiol B 2018 Dec 3;189:55-65. Epub 2018 Oct 3.

Programa Interdisciplinar em Ciências da Saúde, Universidade Federal de São Paulo, UNIFESP, Av. Ana Costa, 95, Santos, SP 11060-001, Brazil; Departamento de Biociências, Universidade Federal de São Paulo, UNIFESP, Rua Silva Jardim, 136, Santos, SP 11015-020, Brazil. Electronic address:

There are no effective therapies for remyelination. Low-level laser therapy (LLLT) has been found advantageous in neurogenesis promotion, cell death prevention, and modulation of inflammation in central and peripheral nervous system models. The purpose of this study was to analyse LLLT effects on cuprizone-induced demyelination. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10111344183036
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http://dx.doi.org/10.1016/j.jphotobiol.2018.09.024DOI Listing
December 2018
18 Reads

Coumarin-dithiocarbamate hybrids as novel multitarget AChE and MAO-B inhibitors against Alzheimer's disease: Design, synthesis and biological evaluation.

Bioorg Chem 2018 12 11;81:512-528. Epub 2018 Sep 11.

National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, PR China. Electronic address:

A series of new coumarin-dithiocarbamate hybrids were designed and synthesized as multitarget agents for the treatment of Alzheimer's disease. Most of them showed potent and clearly selective inhibition towards AChE and MAO-B. Among these compounds, compound 8f demonstrated the most potent inhibition to AChE with IC values of 0. Read More

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http://dx.doi.org/10.1016/j.bioorg.2018.09.010DOI Listing
December 2018
8 Reads
2.152 Impact Factor

Khat: A Substance of Growing Abuse with Adverse Drug Interaction Risks.

Authors:
Worku Abebe

J Natl Med Assoc 2018 Dec 3;110(6):624-634. Epub 2018 May 3.

Department of Oral Biology/Pharmacology, Dental College of Georgia, Augusta University Augusta, GA 30912-1128, USA. Electronic address:

The growing global availability of the stimulant shrub, khat, has aroused widespread concern. This paper is a review of possible adverse interactions between khat and conventional drugs. Khat chewing has been shown to reduce the bioavailabilities of orally co-administered antibiotics, ampicillin, amoxicillin, cephradine and tetracyclineHCl, and the antimalarial drug, chloroquine. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00279684183006
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http://dx.doi.org/10.1016/j.jnma.2018.04.001DOI Listing
December 2018
16 Reads

The Protective Effect of Repeated 1MeTIQ Administration on the Lactacystin-Induced Impairment of Dopamine Release and Decline in TH Level in the Rat Brain.

Neurotox Res 2018 Oct 20;34(3):706-716. Epub 2018 Aug 20.

Department of Neurochemistry, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343, Kraków, Poland.

Parkinson's disease (PD) is a neurodegenerative disorder of the central nervous system (CNS) caused by a progressive loss of nigrostriatal dopaminergic neurons. Dysfunction of the ubiquitin-proteasome system (UPS) plays an important role in the pathogenesis of PD. Intranigral administration of the UPS inhibitor lactacystin is used to obtain a valuable animal model for investigating putative neuroprotective treatments for PD. Read More

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http://dx.doi.org/10.1007/s12640-018-9939-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154174PMC
October 2018
3 Reads

Orthologous proteins of experimental de- and remyelination are differentially regulated in the CSF proteome of multiple sclerosis subtypes.

PLoS One 2018 16;13(8):e0202530. Epub 2018 Aug 16.

Department of Neurology, Odense University Hospital, Odense, Denmark.

Objective: Here, we applied a multi-omics approach (i) to examine molecular pathways related to de- and remyelination in multiple sclerosis (MS) lesions; and (ii) to translate these findings to the CSF proteome in order to identify molecules that are differentially expressed among MS subtypes.

Methods: To relate differentially expressed genes in MS lesions to de- and remyelination, we compared transcriptome of MS lesions to transcriptome of cuprizone (CPZ)-induced de- and remyelination. Protein products of the overlapping orthologous genes were measured within the CSF by quantitative proteomics, parallel reaction monitoring (PRM). Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0202530PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095600PMC
February 2019
10 Reads

Serotonin Toxicity and Urinary Analgesics: A Case Report and Systematic Literature Review of Methylene Blue-Induced Serotonin Syndrome.

Psychosomatics 2018 11 3;59(6):539-546. Epub 2018 Jul 3.

James A. Haley Veterans' Hospital, Mental Health and Behavioral Sciences Service, University of South Florida, Psychiatry and Behavioral Neurosciences, Tampa, FL; University of Iowa Roy J and Lucille A Carver College of Medicine, Department of Psychiatry, Iowa City, IA.

Background: Serotonin syndrome (SS) is a potentially serious side effect of serotonergic drugs. Cases of SS have been reported from the administration of methylene blue (MB), an agent with monoamine oxidase inhibiting properties. To date, the reported cases of MB-induced SS have all been with MB given parenterally. Read More

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http://dx.doi.org/10.1016/j.psym.2018.06.012DOI Listing
November 2018
9 Reads

Donepezil-butylated hydroxytoluene (BHT) hybrids as Anti-Alzheimer's disease agents with cholinergic, antioxidant, and neuroprotective properties.

Eur J Med Chem 2018 Sep 4;157:161-176. Epub 2018 Aug 4.

Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, PR China. Electronic address:

The multifactorial nature of Alzheimer's disease (AD) calls for the development of multitarget agents addressing key pathogenic processes. A novel family of donepezil-butylated hydroxytoluene (BHT) hybrids were designed, synthesized and evaluated as multifunctional ligands against AD. The optimal compound 7d displayed a balanced multifunctional profile covering an intriguing acetylcholinesterase (AChE) inhibition (IC 0. Read More

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http://dx.doi.org/10.1016/j.ejmech.2018.08.005DOI Listing
September 2018
15 Reads
3.450 Impact Factor

Impairment of frequency-specific responses associated with altered electrical activity patterns in auditory thalamus following focal and general demyelination.

Exp Neurol 2018 11 23;309:54-66. Epub 2018 Jul 23.

Institute of Physiology I, University of Münster, Münster, Germany. Electronic address:

Multiple sclerosis is characterized by intermingled episodes of de- and remyelination and the occurrence of white- and grey-matter damage. To mimic the randomly distributed pathophysiological brain lesions observed in MS, we assessed the impact of focal white and grey matter demyelination on thalamic function by directing targeted lysolecithin-induced lesions to the capsula interna (CI), the auditory cortex (A1), or the ventral medial geniculate nucleus (vMGN) in mice. Pathophysiological consequences were compared with those of cuprizone treatment at different stages of demyelination and remyelination. Read More

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http://dx.doi.org/10.1016/j.expneurol.2018.07.010DOI Listing
November 2018
3 Reads

Methylene Blue Analogues with Marginal Monoamine Oxidase Inhibition Retain Antidepressant-like Activity.

ACS Chem Neurosci 2018 Dec 25;9(12):2917-2928. Epub 2018 Jul 25.

Pharmaceutical Chemistry, School of Pharmacy , North-West University , Private Bag X6001 , Potchefstroom 2520 , South Africa.

Methylene blue (MB) possesses diverse medical applications. Among these, MB presents with antidepressant-like effects in animals and has shown promise in clinical trials for the treatment of mood disorders. As an antidepressant, MB may act via various mechanisms which include modulation of the nitric oxide cyclic guanosine monophosphate (NO-cGMP) cascade, enhancement of mitochondrial respiration and antioxidant effects. Read More

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http://dx.doi.org/10.1021/acschemneuro.8b00042DOI Listing
December 2018
6 Reads

Tamarind seed coat extract restores fluoride-induced hematological and biochemical alterations in rats.

Environ Sci Pollut Res Int 2018 Sep 4;25(26):26157-26166. Epub 2018 Jul 4.

Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore, Tamilnadu, 641 046, India.

Fluoride (F) is becoming an ineluctable environmental pollutant causing deleterious effects in humans. In the present study, we examined whether tamarind seed coat extract (TSCE) is beneficial against the F-induced systemic toxicity and hematological changes. Wistar rats were randomly grouped as follows: group I served as control; group II intoxicated with sodium fluoride (NaF, 300 ppm) in drinking water; group III was administered through oral intubation with TSCE (100 mg/kg bw); group IV was treated with NaF (300 ppm) in association with TSCE (100 mg/kg bw) for 30 days. Read More

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http://dx.doi.org/10.1007/s11356-018-2667-xDOI Listing
September 2018
2 Reads
2.830 Impact Factor

Sulfasalazine alters microglia phenotype by competing endogenous RNA effect of miR-136-5p and long non-coding RNA HOTAIR in cuprizone-induced demyelination.

Biochem Pharmacol 2018 09 23;155:110-123. Epub 2018 Jun 23.

Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China. Electronic address:

Sulfasalazine (SF) promotes remyelination and improves the outcome of multiple sclerosis (MS) patients. However, the underlining mechanism remains elusive. Here, we examined whether SF blocks microglia switching to a pro-inflammatory M1-like phenotype through a competing endogenous RNA (ceRNA) effects in cuprizone-induced demyelination. Read More

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http://dx.doi.org/10.1016/j.bcp.2018.06.028DOI Listing
September 2018
30 Reads
5.010 Impact Factor

Opioid analgesic drugs and serotonin toxicity (syndrome): mechanisms, animal models, and links to clinical effects.

Authors:
Brian A Baldo

Arch Toxicol 2018 Aug 18;92(8):2457-2473. Epub 2018 Jun 18.

Molecular Immunology Unit, Department of Medicine, Kolling Institute of Medical Research, Royal North Shore Hospital of Sydney, University of Sydney, Sydney, NSW, Australia.

Drugs may cause serotonin toxicity by a number of different mechanisms including inhibition of serotonin uptake and metabolism, increased serotonin synthesis and release, activation of serotonin receptors, and inhibition of cytochrome P450 oxidases. Some drug interactions involving opioids can increase intrasynaptic levels of serotonin, and opioid analgesic drugs are now recognized as being involved in some cases of serotonin toxicity especially if administered in conjunction with other serotonergic medications including monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants. In March 2016, the FDA issued a Drug Safety Communication concerning the association of the entire class of opioid pain medicines with serotonin toxicity. Read More

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http://dx.doi.org/10.1007/s00204-018-2244-6DOI Listing
August 2018
13 Reads

Quantitative analysis of in-vivo responses of reproductive and thyroid endpoints in male goldfish exposed to monocrotophos pesticide.

Comp Biochem Physiol C Toxicol Pharmacol 2018 Sep 25;211:41-47. Epub 2018 May 25.

College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China. Electronic address:

Cross-regulation occurs at many points between the hypothalamic-pituitary-gonad (HPG) and hypothalamic-pituitary-thyroid (HPT) axes. Monocrotophos (MCP) pesticide could disrupt HPG and HPT axes, but its direct target within the endocrine system is still unclear. In the present study, hormone concentrations and transcriptional profiles of HPG and HPT genes were examined in male goldfish (Carassius auratus) exposed to 0, 4, 40, and 400 μg/L MCP for 2, 4, 8, and 12 d. Read More

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http://dx.doi.org/10.1016/j.cbpc.2018.05.010DOI Listing
September 2018
6 Reads

Insights on the age dependent neurodegeneration induced by Monocrotophos, (an organophosphorous insecticide) in Caenorhabditis elegans fed high glucose: Evidence in wild and transgenic strains.

Comp Biochem Physiol C Toxicol Pharmacol 2018 Sep 12;211:15-24. Epub 2018 May 12.

Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, New Delhi, India; Department of Food Protectants and Infestation Control, CSIR-Central Food Technological Research Institute, Mysore 570 020, India. Electronic address:

The higher susceptibility of high glucose fed C. elegans to Monocrotophos (MCP, an organophosphorus insecticide) - induced dopaminergic (DA) neuronal degeneration was recently demonstrated. Employing this acute exposure model, the impact of MCP on DA degeneration among worms of two age groups (8 and 13 d old) fed control (CO) and high glucose (GF) diet with specific focus on phenotypic alterations, oxidative impairments and associated molecular perturbations employing both wild (N2) and transgenic strains(BZ555 and NL5901) was investigated. Read More

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http://dx.doi.org/10.1016/j.cbpc.2018.05.002DOI Listing
September 2018
4 Reads

Biochemically altered myelin triggers autoimmune demyelination.

Proc Natl Acad Sci U S A 2018 05 4;115(21):5528-5533. Epub 2018 May 4.

Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary Cumming School of Medicine, Calgary, AB T2N 4N1, Canada;

Although immune attack against central nervous system (CNS) myelin is a central feature of multiple sclerosis (MS), its root cause is unresolved. In this report, we provide direct evidence that subtle biochemical modifications to brain myelin elicit pathological immune responses with radiological and histological properties similar to MS lesions. A subtle myelinopathy induced by abbreviated cuprizone treatment, coupled with subsequent immune stimulation, resulted in lesions of inflammatory demyelination. Read More

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http://dx.doi.org/10.1073/pnas.1721115115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003499PMC
May 2018
17 Reads

Selegiline Nanoformulation in Attenuation of Oxidative Stress and Upregulation of Dopamine in the Brain for the Treatment of Parkinson's Disease.

Rejuvenation Res 2018 Oct 21;21(5):464-476. Epub 2018 Jun 21.

1 Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard (Hamdard University) , New Delhi, India .

Objective of this study was to determine whether the prepared nanoemulsion would be able to deliver selegiline to the brain by intranasal route, improving its bioavailability. Antioxidant activity, pharmacokinetic parameters, and dopamine concentration were determined. Oxidative stress models, which had Parkinson's disease-like symptoms, were used to evaluate the antioxidant activity of nanoemulsion loaded with selegiline in vivo. Read More

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http://dx.doi.org/10.1089/rej.2017.2035DOI Listing
October 2018
2 Reads

Microglial MHC class II is dispensable for experimental autoimmune encephalomyelitis and cuprizone-induced demyelination.

Eur J Immunol 2018 08 7;48(8):1308-1318. Epub 2018 Jun 7.

Departments of Immunology, Weizmann Institute of Science, Rehovot, Israel.

Microglia are resident immune cells in the CNS, strategically positioned to clear dead cells and debris, and orchestrate CNS inflammation and immune defense. In steady state, these macrophages lack MHC class II (MHCII) expression, but microglia activation can be associated with MHCII induction. Whether microglial MHCII serves antigen presentation for critical local T-cell restimulation in CNS auto-immune disorders or modulates microglial signaling output remains under debate. Read More

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http://dx.doi.org/10.1002/eji.201847540DOI Listing
August 2018
6 Reads

Mitochondria-targeted prostate cancer therapy using a near-infrared fluorescence dye-monoamine oxidase A inhibitor conjugate.

J Control Release 2018 06 19;279:234-242. Epub 2018 Apr 19.

Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address:

Prostate cancer (PCa) is the most frequent malignant cancer among men in the USA, leading to substantial morbidity and mortality, while the existing treatments have restricted therapeutic benefits for patients with hormone-refractory PCa (HRPC) and metastatic PCa. Recent studies show that advanced PCa exhibits an increase in the expression of monoamine oxidase A (MAOA) which is a mitochondria enzyme, and MAOA activity inhibition could restrict metastasis and extend mice survival in PCa xenografts. These findings suggest MAOA can be a potential target to treat PCa. Read More

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http://dx.doi.org/10.1016/j.jconrel.2018.04.038DOI Listing
June 2018
5 Reads

Proposing Novel MAO-B Hit Inhibitors Using Multidimensional Molecular Modeling Approaches and Application of Binary QSAR Models for Prediction of Their Therapeutic Activity, Pharmacokinetic and Toxicity Properties.

ACS Chem Neurosci 2018 Jul 7;9(7):1768-1782. Epub 2018 May 7.

Department of Chemistry , Istanbul Technical University , Istanbul 34469 , Turkey.

Monoamine oxidase (MAO) enzymes MAO-A and MAO-B play a critical role in the metabolism of monoamine neurotransmitters. Hence, MAO inhibitors are very important for the treatment of several neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). In this study, 256 750 molecules from Otava Green Chemical Collection were virtually screened for their binding activities as MAO-B inhibitors. Read More

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http://dx.doi.org/10.1021/acschemneuro.8b00095DOI Listing
July 2018
3 Reads

AATYK is a Novel Regulator of Oligodendrocyte Differentiation and Myelination.

Neurosci Bull 2018 Jun 19;34(3):527-533. Epub 2018 Mar 19.

Institute of Developmental and Regenerative Biology, Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, 310036, China.

Oligodendrocytes (OLs) are myelinating glial cells that form myelin sheaths around axons to ensure rapid and focal conduction of action potentials. Here, we found that an axonal outgrowth regulatory molecule, AATYK (apoptosis-associated tyrosine kinase), was up-regulated with OL differentiation and remyelination. We therefore studied its role in OL differentiation. Read More

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http://dx.doi.org/10.1007/s12264-018-0218-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5960454PMC
June 2018
4 Reads

Cytotoxic and Apoptotic Activity of the Novel Harmine Derivative ZC-14 in Sf9 Cells.

Int J Mol Sci 2018 Mar 11;19(3). Epub 2018 Mar 11.

Key Laboratory of Crop Integrated Pest Management in South China, Ministry of Agriculture, South China Agricultural University, Guangzhou 510642, China.

Harmine, one of the natural β-carboline alkaloids extracted from L., exhibits broad spectrum but limited insecticidal ability against many pests. So there is an urgent need to synthesize novel derivatives with high efficiency. Read More

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http://dx.doi.org/10.3390/ijms19030811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877672PMC
March 2018
6 Reads

Synthesis, Biological Evaluation and Molecular Modeling Studies of Propargyl-Containing 2,4,6-Trisubstituted Pyrimidine Derivatives as Potential Anti-Parkinson Agents.

ChemMedChem 2018 04 13;13(7):705-712. Epub 2018 Mar 13.

Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, Mansa Road, Bathinda, Punjab, 151001, India.

Monoamine oxidase B (MAO-B) inhibitors are potential drug candidates for the treatment of various neurological disorders including Parkinson's disease. A total of 20 new propargyl-containing 2,4,6-trisubstituted pyrimidine derivatives were synthesized and screened for MAO inhibition using Amplex Red assays. All the synthesized compounds were found to be reversible and selective inhibitors of the MAO-B isoform at sub-micromolar concentrations. Read More

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http://dx.doi.org/10.1002/cmdc.201700589DOI Listing
April 2018
1 Read

Resveratrol Prevents the Cellular Damages Induced by Monocrotophos via PI3K Signaling Pathway in Human Cord Blood Mesenchymal Stem Cells.

Mol Neurobiol 2018 Nov 10;55(11):8278-8292. Epub 2018 Mar 10.

System Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), MG Marg, Lucknow, Uttar Pradesh, 226001, India.

The role of resveratrol (RV) as a neuroprotectant is well recognized, and cellular molecules involved in imparting the physiological effect have been well illustrated. However, some ambiguity still prevails as the specific receptor, and downstream signaling molecules are not yet clearly stated. So, we investigated the signaling pathway(s) involved in its cellular protection in the human umbilical cord blood mesenchymal stem cell (hUCB-MSC) derived neuronal cells. Read More

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http://dx.doi.org/10.1007/s12035-018-0986-zDOI Listing
November 2018
2 Reads

Suppression of Non-Small Cell Lung Cancer Growth and Metastasis by a Novel Small Molecular Activator of RECK.

Cell Physiol Biochem 2018 28;45(5):1807-1817. Epub 2018 Feb 28.

Research Center of Basic Medical Sciences, School of Basic Medical Sciences, Hubei University of Science and Technology, Xianning, China.

Background/aims: Reversion-inducing cysteine-rich protein with kazal motifs (RECK) is a novel tumor suppressor gene that is critical for regulating tumor cell invasion and metastasis. The expression of RECK is dramatically down-regulated in human cancers. Harmine, a tricyclic compound from Peganum harmala, has been shown to have potential anti-cancer activity. Read More

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http://dx.doi.org/10.1159/000487872DOI Listing
May 2018
17 Reads

Harmines inhibit cancer cell growth through coordinated activation of apoptosis and inhibition of autophagy.

Biochem Biophys Res Commun 2018 03 1;498(1):99-104. Epub 2018 Mar 1.

Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, People's Republic of China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drug Research, Jinan University, Guangzhou 510632, People's Republic of China. Electronic address:

Harmine and its analogs have long been considered as anticancer agents. In vitro analyses suggested that intercalating DNA or inhibiting topoisomerase might contribute to the cytotoxic effect of this class of compound. However, this idea has not been rigorously tested in intact cells. Read More

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http://dx.doi.org/10.1016/j.bbrc.2018.02.205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5857254PMC
March 2018
7 Reads

An iminium ion metabolite hampers the production of the pharmacologically active metabolite of a multikinase inhibitor KW-2449 in primates: irreversible inhibition of aldehyde oxidase and covalent binding with endogenous proteins.

Biopharm Drug Dispos 2018 Mar;39(3):164-174

School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1 Katakura-cho, Hachioji, Tokyo, 192-0983, Japan.

We previously reported that KW-2449, (E)-1-{4-[2-(1H-Indazol-3-yl)vinyl]benzoyl}piperazine, a novel multikinase inhibitor developed for the treatment of leukemia patients, was oxidized to an iminium ion intermediate by monoamine oxidase B (MAO-B) and then converted to its oxo-piperazine form (M1) by aldehyde oxidase (AO). However, it was found that the significant decrease in the pharmacologically active metabolite M1 following repeated administration of KW-2449 in primates might hamper the effectiveness of the drug. The mechanism underlying this phenomenon was investigated and it was found that the AO activity was inhibited in a time-dependent manner in vitro under the co-incubation of KW-2449 and MAO-B, while neither KW-2449 nor M1 strongly inhibited MAO-B or AO activity. Read More

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http://dx.doi.org/10.1002/bdd.2123DOI Listing
March 2018
6 Reads

A novel harmine derivative, N-(4-(hydroxycarbamoyl)benzyl)-1-(4- methoxyphenyl)-9H-pyrido[3,4-b]indole-3-carboxamide (HBC), as histone deacetylase inhibitor: in vitro antiproliferation, apoptosis induction, cell cycle arrest, and antimetastatic effects.

Eur J Pharmacol 2018 Apr 9;824:78-88. Epub 2018 Feb 9.

The Affiliated Hospital of Nantong University, Nantong University, Nantong 226001, PR China; School of Pharmacy and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, PR China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address:

This study aims to design and synthesize a novel harmine derivative N-(4-(hydroxycarbamoyl) benzyl)-1-(4-methoxyphenyl)-9H-pyrido [3,4-b]indole-3-carboxamide (HBC) as histone deacetylase (HDAC) inhibitor, and evaluate its antitumor activities and anti-metastasis mechanism. HBC not only exerted significant ant-proliferation activity against five human cancer cell lines, especially for HepG2 cell with an IC value of 2.21 μM, which is nearly three-fold lower than SAHA (IC = 6. Read More

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http://dx.doi.org/10.1016/j.ejphar.2018.02.004DOI Listing
April 2018
15 Reads

Design, synthesis and evaluation of 4'-OH-flurbiprofen-chalcone hybrids as potential multifunctional agents for Alzheimer's disease treatment.

Bioorg Med Chem 2018 03 2;26(5):1102-1115. Epub 2018 Feb 2.

Department of Medicinal Chemistry, Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. Electronic address:

A series of 4'-OH-flurbiprofen-chalcone hybrids were designed, synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease. The biological screening results indicated that most of these hybrids exhibited good multifunctional activities. Among them, compounds 7k and 7m demonstrated the best inhibitory effects on self-induced Aβ aggregation (60. Read More

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http://dx.doi.org/10.1016/j.bmc.2018.01.030DOI Listing
March 2018
10 Reads

Effect of Multiple Intraperitoneal Injections of Human Bone Marrow Mesenchymal Stem Cells on Cuprizone Model of Multiple Sclerosis

Iran Biomed J 2018 09 7;22(5):312-21. Epub 2018 Feb 7.

Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Background: Bone marrow mesenchymal stem cells (BM-MSCs) elicit neuroprotective effects, and their repair ability has been investigated in different experimental models. We aimed to investigate the effect of multiple i.p. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6058183PMC
September 2018
3 Reads

Selective dopaminergic neurotoxicity of three heterocyclic amine subclasses in primary rat midbrain neurons.

Neurotoxicology 2018 03;65:68-84

School of Health Sciences, Purdue University, West Lafayette, IN, 47907, United States; Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN, 47907, United States. Electronic address:

Heterocyclic amines (HCAs) are primarily produced during high temperature meat cooking. These compounds have been intensively investigated as mutagens and carcinogens. However, converging data suggest that HCAs may also be neurotoxic and potentially relevant to neurodegenerative diseases such as Parkinson's disease (PD). Read More

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http://dx.doi.org/10.1016/j.neuro.2018.01.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015749PMC
March 2018
3 Reads

Isatin, an endogenous nonpeptide biofactor: A review of its molecular targets, mechanisms of actions, and their biomedical implications.

Biofactors 2018 Mar 16;44(2):95-108. Epub 2018 Jan 16.

Department of Proteomic Research and Mass Spectrometry, Institute of Biomedical Chemistry, Moscow, Russia.

Isatin (indole-2,3-dione) is an oxidized indole. It is widely distributed in mammalian tissues and body fluids, where isatin concentrations vary significantly from <0.1 to > 10 µM. Read More

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http://dx.doi.org/10.1002/biof.1408DOI Listing
March 2018
17 Reads

Quantitative analysis of lipid debris accumulation caused by cuprizone induced myelin degradation in different CNS areas.

Brain Res Bull 2018 03 8;137:277-284. Epub 2018 Jan 8.

MTA-SZTE Research Group for Cortical Microcircuits, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, Szeged H-6726, Hungary. Electronic address:

Degradation of myelin sheath is thought to be the cause of neurodegenerative diseases, such as multiple sclerosis (MS), but definitive agreement on the mechanism of how myelin is lost is currently lacking. Autoimmune initiation of MS has been recently questioned by proposing that the immune response is a consequence of oligodendrocyte degeneration. To study the process of myelin breakdown, we induced demyelination with cuprizone and applied coherent anti-Stokes Raman scattering (CARS) microscopy, a non-destructive label-free method to image lipid structures in living tissue. Read More

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http://dx.doi.org/10.1016/j.brainresbull.2018.01.003DOI Listing
March 2018
11 Reads

Genetics and Treatment Response in Parkinson's Disease: An Update on Pharmacogenetic Studies.

Neuromolecular Med 2018 03 5;20(1):1-17. Epub 2018 Jan 5.

Department of Biomedicine and Prevention, Genetics Section, University of Rome "Tor Vergata", Via Montpellier 1, 00133, Rome, Italy.

Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by a progressive loss of dopamine neurons of the central nervous system. The disease determines a significant disability due to a combination of motor symptoms such as bradykinesia, rigidity and rest tremor and non-motor symptoms such as sleep disorders, hallucinations, psychosis and compulsive behaviors. The current therapies consist in combination of drugs acting to control only the symptoms of the illness by the replacement of the dopamine lost. Read More

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http://dx.doi.org/10.1007/s12017-017-8473-7DOI Listing
March 2018
10 Reads

Phenelzine reduces the oxidative damage induced by peroxynitrite in plasma lipids and proteins.

Arch Physiol Biochem 2018 Dec 19;124(5):418-423. Epub 2017 Dec 19.

a School of Medicine , Jordan University of Science and Technology , Irbid , Jordan.

Peroxynitrite is a reactive nitrogen species produced in the intravascular compartment from superoxide anion and nitric oxide. Peroxynitrite destroys blood plasma proteins and membranes of red blood cells and of platelets. This explains why excessive production of peroxynitrite contributes to diseases and to ageing. Read More

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http://dx.doi.org/10.1080/13813455.2017.1415939DOI Listing
December 2018
12 Reads

Therapeutic Role of Harmalol Targeting Nucleic Acids: Biophysical Perspective and in vitro Cytotoxicity.

Mini Rev Med Chem 2018 ;18(19):1624-1639

Department of Zoology, University of Kalyani, Nadia, West Bengal, 741235, India.

Background: Harmalol, a beta carboline alkaloid, shows remarkable importance in the contemporary biomedical research and drug discovery programs. With time, there is emerging interest in search for better anti-cancer drugs of plant origin with high activity and lower toxicity. Most of the chemotherapeutic agents due to their non-specific target and toxicity on active healthy cells, use is often restricted, necessitating search for newer drugs having greater potentiality. Read More

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http://dx.doi.org/10.2174/1389557518666171211164830DOI Listing
December 2018
5 Reads