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https://www.readbyqxmd.com/read/28722470/novel-potent-inhibitors-of-the-histone-demethylase-kdm1a-lsd1-orally-active-in-a-murine-promyelocitic-leukemia-model
#1
Paolo Trifirò, Anna Cappa, Silvia Brambillasca, Oronza A Botrugno, Maria Rosaria Cera, Roberto Dal Zuffo, Paola Dessanti, Giuseppe Meroni, Florian Thaler, Manuela Villa, Saverio Minucci, Ciro Mercurio, Mario Varasi, Paola Vianello
BACKGROUND: Histone lysine demethylases (KDMs) are well-recognized targets in oncology drug discovery. They function at the post-translation level controlling chromatin conformation and gene transcription. KDM1A is a flavin adenine dinucleotide-dependent amine oxidase, overexpressed in several tumor types, including acute myeloid leukemia, neuroblastoma and non-small-cell lung cancer. Among the many known monoamine oxidase inhibitors screened for KDM1A inhibition, tranylcypromine emerged as a moderately active hit, which irreversibly binds to the flavin adenine dinucleotide cofactor...
July 19, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28722111/monoamine-oxidase-a-is-highly-expressed-in-classical-hodgkin-lymphoma
#2
Pei Chuan Li, Imran N Siddiqi, Anja Mottok, Eric Y Loo, Chieh Hsi Wu, Wendy Cozen, Christian Steidl, Jean Chen Shih
Monoamine oxidase A (MAOA) is a mitochondrial enzyme that catalyzes oxidative deamination of neurotransmitters and dietary amines and produces H2 O2. It facilitates the progression of gliomas and prostate cancer, but its expression and functional relevance have not been studied in lymphoma. Here, we evaluated MAOA in 427 cases of Hodgkin and non-Hodgkin lymphoma and in a spectrum of reactive lymphoid tissues by immunohistochemistry on formalin-fixed paraffin-embedded specimens. MAOA was expressed by Hodgkin Reed-Sternberg (HRS) cells in the majority of classical Hodgkin lymphomas (cHL) (181/241; 75%), with 34...
July 19, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28720478/monoamine-receptor-interaction-profiles-of-4-thio-substituted-phenethylamines-2c-t-drugs
#3
REVIEW
Dino Luethi, Daniel Trachsel, Marius C Hoener, Matthias E Liechti
BACKGROUND: 4-Thio-substituted phenethylamines (2C-T drugs) are potent psychedelics with poorly defined pharmacological properties. Because of their psychedelic effects, 2C-T drugs are sometimes sold as new psychoactive substances (NPSs). The aim of the present study was to characterize the monoamine receptor and transporter interaction profiles of a series of 2C-T drugs. METHODS: We determined the binding affinities of 2C-T drugs at monoamine receptors and transporters in human cells that were transfected with the respective receptors or transporters...
July 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28718334/the-preclinical-discovery-and-development-of-brexpiprazole-for-the-treatment-of-major-depressive-disorder
#4
Awais Aftab, Keming Gao
Brexpiprazole is the most recently approved second-generation antipsychotic, which is used as adjunctive therapy to antidepressants for treating major depressive disorder (MDD) with inadequate response. Brexpiprazole shares pharmacological similarities with other second-generation antipsychotics, especially aripiprazole. Area covered: This review provides a detailed overview of the pre-clinical studies of brexpiprazole, followed by a summary of its clinical studies, and a comparison with other antipsychotics in MDD...
July 18, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28716953/a-novel-in-vitro-analog-expressing-learning-induced-cellular-correlates-in-distinct-neural-circuits
#5
Harris A Weisz, Marcy L Wainwright, Riccardo Mozzachiodi
When presented with noxious stimuli, Aplysia exhibits concurrent sensitization of defensive responses, such as the tail-induced siphon withdrawal reflex (TSWR) and suppression of feeding. At the cellular level, sensitization of the TSWR is accompanied by an increase in the excitability of the tail sensory neurons (TSNs) that elicit the reflex, whereas feeding suppression is accompanied by decreased excitability of B51, a decision-making neuron in the feeding neural circuit. The goal of this study was to develop an in vitro analog coexpressing the above cellular correlates...
August 2017: Learning & Memory
https://www.readbyqxmd.com/read/28716530/genetic-association-analysis-of-serotonin-and-signal-transduction-pathways-in-suicide-attempters-from-an-italian-sample-of-psychiatric-patients
#6
Maurizio Pompili, Giovanna Gentile, Catia Scassellati, Cristian Bonvicini, Marco Innamorati, Denise Erbuto, Franco Montebovi, Giuseppe Ducci, Alberto Forte, Eleonora De Pisa, Stefano Ferracuti, Gianluca Serafini, Vincenzo De Luca, Mario Amore, Maurizio Simmaco, Paolo Girardi
Genetic factors have been reported to contribute to the liability of suicide. We aimed to investigate functional polymorphisms in eight genes (serotonin transporter, SLC6A4; receptors, 5HTR1A, 1B, 5HTR2A; Tryptophan Hydroxylase, TPH1, TPH2; Monoamine Oxidase, MAOA and G Protein Subunit Beta 3, GNB3) to investigate their predictive value for suicide. The possible confounding effects of gender and phenotypic patients dissection were also valued. A sample of 111 consecutive psychiatric inpatients was recruited and assessed using specific psychometric instruments...
July 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28716399/prelimbic-%C3%AE-1-adrenoceptors-are-involved-in-the-regulation-of-depressive-like-behaviors-in-the-hemiparkinsonian-rats
#7
Zhong Heng Wu, Qiao Jun Zhang, Cheng Xue Du, Yue Xi, Wen Juan Li, Fang Yuan Guo, Shu Qi Yu, Ya Xin Yang, Jian Liu
At present, it is not clear whether α1-adrenoceptors in the prelimbic cortex (PrL) are involved in Parkinson's disease-related depression. Here we examined effects of PrL α1-adrenoceptors on depressive-like behaviors in rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. The lesion induced depressive-like responses as measured by the sucrose preference and forced swim tests compared to sham-operated rats. Intra-PrL injection of α1-adrenoceptor agonist phenylephrine induced or increased the expression of depressive-like behaviors in sham-operated and the lesioned rats...
July 14, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28714881/assessment-of-enzyme-inhibition-a-review-with-examples-from-the-development-of-monoamine-oxidase-and-cholinesterase-inhibitory-drugs
#8
REVIEW
Rona R Ramsay, Keith F Tipton
The actions of many drugs involve enzyme inhibition. This is exemplified by the inhibitors of monoamine oxidases (MAO) and the cholinsterases (ChE) that have been used for several pharmacological purposes. This review describes key principles and approaches for the reliable determination of enzyme activities and inhibition as well as some of the methods that are in current use for such studies with these two enzymes. Their applicability and potential pitfalls arising from their inappropriate use are discussed...
July 15, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28714395/five-decades-of-cuprizone-an-updated-model-to-replicate-demyelinating-diseases
#9
Jose M Vega-Riquer, Gerardo Mendez-Victoriano, Raul A Morales-Luckie, Oscar Gonzalez-Perez
Multiple sclerosis, Guillain-Barré syndrome, peripheral nerve polyneuropathy and others comprise a group of demyelinating diseases characterized by progressive (and eventually irreversible) loss of oligodendrocytes and myelin sheaths in the white matter of the brain. To date, the etiology of these disorders is not well known and no effective treatments are currently available. Therefore, further research is needed to gain a better understand and treat these patients. To accomplish this goal, it is necessary to have appropriate animal models that closely resemble the pathophysiology of these diseases...
July 17, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28712090/does-prior-traumatization-affect-the-treatment-outcome-of-cbt-for-panic-disorder-the-potential-role-of-the-maoa-gene-and-depression-symptoms
#10
Sebastian Trautmann, Jan Richter, Markus Muehlhan, Michael Höfler, Hans-Ulrich Wittchen, Katharina Domschke, Andreas Ströhle, Alfons O Hamm, Heike Weber, Tilo Kircher, Volker Arolt, Alexander L Gerlach, Georg W Alpers, Thomas Fydrich, Thomas Lang, Andreas Reif
Although cognitive behavioral therapy (CBT) is highly effective in the treatment of anxiety disorders, many patients still do not benefit. This study investigates whether a history of traumatic event experience is negatively associated with outcomes of CBT for panic disorder. The moderating role of the monoamine oxidase A (MAOA) gene and depression symptoms as well as the association between trauma history and fear reactivity as a potential mechanism are further analyzed. We conducted a post-hoc analysis of 172 male and 60 female patients with panic disorder treated with CBT in a multi-center study...
July 15, 2017: European Archives of Psychiatry and Clinical Neuroscience
https://www.readbyqxmd.com/read/28711308/the-impact-of-scopolamine-pretreatment-on-3-iodothyronamine-t1am-effects-on-memory-and-pain-in-mice
#11
Annunziatina Laurino, Ersilia Lucenteforte, Gaetano De Siena, Laura Raimondi
We previously demonstrated that 3-iodothyronamine (T1AM), a by-product of thyroid hormone metabolism, pharmacologically administered to mice acutely stimulated learning and memory acquisition and provided hyperalgesia with a mechanism which remains to be defined. We now aimed to investigate whether the T1AM effect on memory and pain was maintained in mice pre-treated with scopolamine, a non-selective muscarinic antagonist expected to induce amnesia and, possibly, hyperalgesia. Mice were pre-treated with scopolamine and, after 20min, injected intracerebroventricularly (i...
July 12, 2017: Hormones and Behavior
https://www.readbyqxmd.com/read/28705604/major-depression-and-heart-failure-interest-of-monoamine-oxidase-inhibitors
#12
REVIEW
Sophie Corbineau, Marie Breton, Jeanne Mialet-Perez, Jean-François Costemale-Lacoste
Several physiopathological hypotheses have been studied to explain the link between heart failure (HF) and major depression (MD). An increase of monoamine oxidase (MAO) has recently been found as a factor involved in the development of HF. The aim of this review is to provide a complete overview of the involvement of MAOs in HF comorbidity of MD and to discuss the pharmacological options. Our work highlights the scientific evidence of MAO involvement in the development of HF. Studies focusing on MAO-A seem to have reproducible results on HF, establishing the effect of this enzyme as well as the protective effect of its inhibition...
July 8, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28704274/maternal-separation-induces-long-term-effects-on-monoamines-and-brain-derived-neurotrophic-factor-levels-on-the-frontal-cortex-amygdala-and-hippocampus-differential-effects-after-a-stress-challenge
#13
Soledad Récamier-Carballo, Erika Estrada-Camarena, Carolina López-Rubalcava
The maternal separation (MS) paradigm is a well-known animal model that resembles the stress of early adverse life experiences and produces structural and functional abnormalities when animals are adults. The present study analyzed the effect of MS, in adult mice, on brain-derived neurotrophic factor (BDNF), serotonin (5-HT), and dopamine (DA) levels, and the turnover rate in the hippocampus, frontal cortex, and amygdala, and brain regions that are associated with emotion. Also, the effects of MS in depression-like responses in adult mice were studied...
July 12, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28704190/modulating-effects-of-cholecalciferol-treatment-on-estrogen-deficiency-induced-anxiety-like-behavior-of-adult-female-rats
#14
Julia Fedotova, Daria Zarembo, Jozef Dragasek, Martin Caprnda, Peter Kruzliak, Tatyana Dudnichenko
BACKGROUND: Vitamin D can be one of the candidate substances that are used as additional supplementation in the treatment of anxiety-related disorders in women with estrogen imbalance. MATERIALS AND METHODS: The aim of the present study was to examine the effects of chronic cholecalciferol administration (1.0, 2.5 or 5.0 mg/kg/day, s.c.) on the anxiety-like behavior and monoamines levels in the rat hippocampus following ovariectomy in female rats. Cholecalciferol was given to ovariectomized (OVX) rats and OVX rats treated with 17β-estradiol (17β-E2, 0...
June 1, 2017: Folia Medica
https://www.readbyqxmd.com/read/28700656/unexpected-effects-of-azole-transporter-inhibitors-on-antifungal-susceptibility-in-candida-glabrata-and-other-pathogenic-candida-species
#15
Yohsuke Nagayoshi, Taiga Miyazaki, Shintaro Shimamura, Hironobu Nakayama, Asuka Minematsu, Shunsuke Yamauchi, Takahiro Takazono, Shigeki Nakamura, Katsunori Yanagihara, Shigeru Kohno, Hiroshi Mukae, Koichi Izumikawa
The pathogenic fungus Candida glabrata is often resistant to azole antifungal agents. Drug efflux through azole transporters, such as Cdr1 and Cdr2, is a key mechanism of azole resistance and these genes are under the control of the transcription factor Pdr1. Recently, the monoamine oxidase A (MAO-A) inhibitor clorgyline was shown to inhibit the azole efflux pumps, leading to increased azole susceptibility in C. glabrata. In the present study, we have evaluated the effects of clorgyline on susceptibility of C...
2017: PloS One
https://www.readbyqxmd.com/read/28698144/inhibiting-glycogen-synthase-kinase-3-and-transforming-growth-factor-%C3%AE-signaling-to-promote-epithelial-transition-of-human-adipose-mesenchymal-stem-cells
#16
Melina Setiawan, Xiao-Wei Tan, Tze-Wei Goh, Gary Hin-Fai Yam, Jodhbir S Mehta
BACKGROUND: This study was aimed to investigate the epithelial differentiation of human adipose-derived mesenchymal stem cells (ADSCs) by inhibiting glycogen synthase kinase-3 (GSK3) and transforming growth factor β (TGFβ) signaling. METHODS AND RESULTS: STEMPRO human ADSCs at passage 2 were treated with CHIR99021 (GSK3 inhibitor), E-616452 (TGFβ1 receptor kinase inhibitor), A-83-01 (TGFβ type 1 receptor inhibitor), valproic acid (histone deacetylase inhibitor), tranylcypromine (monoamine oxidase inhibitor) and all-trans retinoic acid for 72 h...
July 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28695536/molecular-mechanisms-underlying-the-anti-depressant-effects-of-resveratrol-a-review
#17
REVIEW
Marcos Roberto de Oliveira, Aline Lukasievicz Chenet, Adriane Ribeiro Duarte, Giselli Scaini, João Quevedo
Major depression is a public health problem, affecting 121 million people worldwide. Patients suffering from depression present high rates of morbidity, causing profound economic and social impacts. Furthermore, patients with depression present cognitive impairments, which could influence on treatment adherence and long-term outcomes. The pathophysiology of major depression is not completely understood yet but involves reduced levels of monoamine neurotransmitters, bioenergetics, and redox disturbances, as well as inflammation and neuronal loss...
July 10, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28694773/loud-noise-exposure-produces-dna-neurotransmitter-and-morphological-damage-within-specific-brain-areas
#18
Giada Frenzilli, Larisa Ryskalin, Michela Ferrucci, Emanuela Cantafora, Silvia Chelazzi, Filippo S Giorgi, Paola Lenzi, Vittoria Scarcelli, Alessandro Frati, Francesca Biagioni, Stefano Gambardella, Alessandra Falleni, Francesco Fornai
Exposure to loud noise is a major environmental threat to public health. Loud noise exposure, apart from affecting the inner ear, is deleterious for cardiovascular, endocrine and nervous systems and it is associated with neuropsychiatric disorders. In this study we investigated DNA, neurotransmitters and immune-histochemical alterations induced by exposure to loud noise in three major brain areas (cerebellum, hippocampus, striatum) of Wistar rats. Rats were exposed to loud noise (100 dBA) for 12 h. The effects of noise on DNA integrity in all three brain areas were evaluated by using Comet assay...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28691859/preliminary-studies-of-berberine-and-its-semi-synthetic-derivatives-as-a-promising-class-of-multi-target-anti-parkinson-agents
#19
Giovanni Ribaudo, Enrico Zanforlin, Marcella Canton, Sergio Bova, Giuseppe Zagotto
Parkinson's disease (PD) is a neurodegenerative disorder bearing motor and nonmotor symptoms. The treatment today is symptomatical rather than preventive or curative and this leaves the field open for the search of both novel molecular targets and drug candidates. Interference with α-synuclein fibrillation, monoamine oxidase (MAO) inhibition, modulation of adenosine receptors and the inhibition of specific phosphodiesterase (PDE) isoforms are some of the currently pursued strategies. We synthesised and studied some semi-synthetic berberine derivatives using a set of in silico tools...
July 10, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28690895/discrimination-between-drug-abuse-and-medical-therapy-case-report-of-a-tranylcypromine-overdose-related-fatality
#20
Maryam Akhgari, Farzaneh Jokar, Afshar Etemadi-Aleagha, Ali Ghasemi
Tranylcypromine is an effective antidepressant from the class of monoamine oxidase inhibitors and is structurally related to amphetamine. However, reports differ regarding the potential metabolism of tranylcypromine to amphetamine and methamphetamine within the human body. We report a 25-year-old woman with severe depression who died due to a fatal tranylcypromine overdose in 2016. She had been prescribed tranylcypromine one day previously and had no history of previous suicide attempts or substance abuse. The body was transferred to a forensic medicine department in Tehran, Iran for the autopsy...
May 2017: Sultan Qaboos University Medical Journal
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