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Drug induced neurological disorders

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https://www.readbyqxmd.com/read/27917413/efficacy-of-s-lacosamide-in-preclinical-models-of-cephalic-pain
#1
Aubin Moutal, Nathan Eyde, Edwin Telemi, Ki Duk Park, Jennifer Y Xie, David W Dodick, Frank Porreca, Rajesh Khanna
Migraine is one of the world's most common neurological disorders. Current acute migraine treatments have sub-optimal efficacy and new therapeutic options are needed. Approaches targeting calcitonin gene related peptide (CGRP) signaling are clinically effective but small molecule antagonists have not been advanced due to toxicity. In this study, we explored the axonal growth/specification collapsin response mediator protein 2 (CRMP2) as a novel "druggable" target for inhibiting CGRP release and for potential relevance for treatment of migraine pain...
June 2016: Pain Reports (Baltimore, Md.)
https://www.readbyqxmd.com/read/27902448/rasgrp1-promotes-amphetamine-induced-motor-behavior-through-a-rhes-interaction-network-rhesactome-in-the-striatum
#2
Neelam Shahani, Supriya Swarnkar, Vincenzo Giovinazzo, Jenny Morgenweck, Laura M Bohn, Catherina Scharager-Tapia, Bruce Pascal, Pablo Martinez-Acedo, Kshitij Khare, Srinivasa Subramaniam
The striatum of the brain coordinates motor function. Dopamine-related drugs may be therapeutic to patients with striatal neurodegeneration, such as Huntington's disease (HD) and Parkinson's disease (PD), but these drugs have unwanted side effects. In addition to stimulating the release of norepinephrine, amphetamines, which are used for narcolepsy and attention-deficit/hyperactivity disorder (ADHD), trigger dopamine release in the striatum. The guanosine triphosphatase Ras homolog enriched in the striatum (Rhes) inhibits dopaminergic signaling in the striatum, is implicated in HD and L-dopa-induced dyskinesia, and has a role in striatal motor control...
November 15, 2016: Science Signaling
https://www.readbyqxmd.com/read/27884751/a-systematic-review-of-the-effect-of-cannabidiol-on-cognitive-function-relevance-to-schizophrenia
#3
REVIEW
Ashleigh L Osborne, Nadia Solowij, Katrina Weston-Green
BACKGROUND AND OBJECTIVES: Cognitive impairment is a core symptom domain of schizophrenia, neurological disorders and substance abuse. It is characterised by deficits in learning, memory, attention and executive functioning and can severely impact daily living. Antipsychotic drugs prescribed to treat schizophrenia provide limited cognitive benefits and novel therapeutic targets are required. Cannabidiol (CBD), a component of the cannabis plant, has anti-inflammatory and antipsychotic-like properties; however, its ability to improve cognitive impairment has not been thoroughly explored...
November 21, 2016: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/27879670/the-protective-effects-of-icariin-against-the-homocysteine-induced-neurotoxicity-in-the-primary-embryonic-cultures-of-rat-cortical-neurons
#4
Xiao-Ang Li, Yuen-Shan Ho, Lei Chen, W L Wendy Hsiao
Icariin, an ingredient in the medicinal herb Epimedium brevicornum Maxim (EbM), has been considered as a potential therapeutic agent for neurodegenerative diseases such as Alzheimer's disease (AD). Hyperhomocysteinaemia is a risk factor for AD and other associated neurological diseases. In this study we aim to investigate whether icariin can reverse homocysteine (Hcy)-induced neurotoxicity in primary embryonic cultures of rat cortical neurons. Our findings demonstrated that icariin might be able restore the cytoskeleton network damaged by Hcy through the modulation of acetyl-α-tubulin, tyrosinated-α-tubulin, and phosphorylation of the tubulin-binding protein Tau...
November 22, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27871881/targeting-brain-and-peripheral-plasticity-of-the-lipidome-in-acute-kainic-acid-induced-epileptic-seizures-in-mice-via-quantitative-mass-spectrometry
#5
Raissa Lerner, Julia Post, Sebastian Loch, Beat Lutz, Laura Bindila
Epilepsy is a highly common chronic neurological disorder, manifested in many different types, affecting ~1% of the worldwide human population. The molecular mechanisms of epileptogenesis has not yet been clarified, and pharmacoresistance exhibited by 30-40% of epilepsy patients remains a major obstacle in medical care. Growing evidence indicates a role of lipid signalling pathways in epileptogenesis, thus lipid signals emerge as potential biomarkers for the onset and evolving course of the epileptic disorder, as well as potential therapeutic agents and targets...
November 15, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27855137/garcinol-upregulates-gabaa-and-gad65-expression-modulates-bdnf-trkb-pathway-to-reduce-seizures-in-pentylenetetrazole-ptz-induced-epilepsy
#6
Fang Hao, Li-Hua Jia, Xiao-Wan Li, Ying-Rui Zhang, Xue-Wu Liu
BACKGROUND Epilepsy is the most predominant neurological disorder characterized by recurrent seizures. Despite treatment with antiepileptic drugs, epilepsy still is a challenge to treat, due to the associated adverse effects of the drugs. Previous investigations have shown critical roles of BDNF-TrkB signalling and expression of glutamic acid decarboxylase 65 (GAD65) and GABAA in the brain during epilepsy. Thus, drugs that could modulate BDNF-TrkB signal and expression of GAD65 and GABAA could aid in therapy...
November 17, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27843822/impact-of-antiepileptic-drugs-on-bone-health-need-for-monitoring-treatment-and-prevention-strategies
#7
REVIEW
Ekta Arora, Harmanjit Singh, Yogendra Kumar Gupta
Epilepsy is the most common neurological disorder affecting approximately 50 million people worldwide. In India, overall prevalence of epilepsy is reported to be 5.59/1000 population. Antiepileptic drugs (AEDs) constitute the main-stay of treatment with a large number of AEDs available in the market. High incidence of adverse effects is a major limitation with AEDs. One of the major concerns is significant metabolic effects on the bone. However, little attention has been paid to this issue because most of the bone effects remain subclinical for a long time and may take years to manifest clinically...
April 2016: Journal of Family Medicine and Primary Care
https://www.readbyqxmd.com/read/27829340/preclinical-evaluation-of-avn-322-novel-and-highly-selective-5-ht6-receptor-antagonist-for-the-treatment-of-alzheimer-s-disease
#8
Alexandre V Ivachtchenko, Yan A Ivanenkov, Mark S Veselov
Alla Chem LLC, Hallandale Beach, USA; bAvineuro Pharmaceuticals, Inc., Hallandale Beach, USA; cMoscow Institute of Physics and Technology (State University), Dolgoprudny city, Russian Federation. Abstract: In recent years, 5-hydroxytryptamine subtype 6 receptor (5-HT6 receptor, 5-HT6R) has rapidly emerged as a promising therapeutic target for the treatment of neuropathological disorders, including Alzheimer's disease (AD). Evidence indicates that 5-HT6 receptors are deeply implicated in the processes of learning and memory, while 5-HT6R antagonists were shown to improve cognition in animal models of cognitive impairment...
November 7, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27825017/a-pharmacological-overview-of-lamotrigine-for-the-treatment-of-epilepsy
#9
Venkata Ramesh Yasam, Satya Lavanya Jakki, V Senthil, M Eswaramoorthy, S Shanmuganathan, K Arjunan, M J Nanjan
Epilepsy is one of the most common neurological disorders, affecting about 2% of the population worldwide. Lamotrigine (LTG) is a second generation anti-epileptic drug (AED) with broad spectrum of activity, a favourable side-effect profile, simpler dosing than earlier drugs and efficacious in diverse epilepsy syndromes. Areas covered: The present review focuses on pharmacodynamics, pharmacokinetics, clinical efficacy, safety and tolerability of LTG and its effect on cognition, psychiatry, quality of life, women and pregnancy along with effect of enzyme inducing and enzyme inhibiting drugs over LTG and their effect on serum level fluctuations by collecting data from various studies over the years until 2016...
December 2016: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/27819315/sustained-synchronized-neuronal-network-activity-in-a-human-astrocyte-co-culture-system
#10
Jacobine Kuijlaars, Tutu Oyelami, Annick Diels, Jutta Rohrbacher, Sofie Versweyveld, Giulia Meneghello, Marianne Tuefferd, Peter Verstraelen, Jan R Detrez, Marlies Verschuuren, Winnok H De Vos, Theo Meert, Pieter J Peeters, Miroslav Cik, Rony Nuydens, Bert Brône, An Verheyen
Impaired neuronal network function is a hallmark of neurodevelopmental and neurodegenerative disorders such as autism, schizophrenia, and Alzheimer's disease and is typically studied using genetically modified cellular and animal models. Weak predictive capacity and poor translational value of these models urge for better human derived in vitro models. The implementation of human induced pluripotent stem cells (hiPSCs) allows studying pathologies in differentiated disease-relevant and patient-derived neuronal cells...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27799045/therapeutic-potential-of-drugs-targeting-pathophysiology-of-intracerebral-hemorrhage-from-animal-models-to-clinical-applications
#11
Kuo-Hsing Liao, Chih-Wei Sung, Ya-Ni Huang, Wei-Jiun Li, Po-Chuan Yu, Jia-Yi Wang
BACKGROUND: Intracerebral hemorrhage (ICH) is one of the most common forms of cerebral hemorrhage, the morbidity and death of ICH is high worldwide. ICH can be spontaneous or caused by hypertension, coagulopathy, angiopathy, head trauma, bleeding disorders, tumors, or drug usage. ICH is the most serious and least treatable form of hemorrhagic stroke, with rapidly increasing hematoma size and often resulting in significant brain injury and long term neurological deficits. Surgical hematoma evacuation remains controversial...
October 27, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27793771/lithium-increases-synaptic-glua2-in-hippocampal-neurons-by%C3%A2-elevating-the-%C3%AE-catenin-protein
#12
Mobeen Farooq, Seonil Kim, Sunny Patel, Latika Khatri, Takuya Hikima, Margaret E Rice, Edward B Ziff
Lithium (Li(+)) is a drug widely employed for treating bipolar disorder, however the mechanism of action is not known. Here we study the effects of Li(+) in cultured hippocampal neurons on a synaptic complex consisting of δ-catenin, a protein associated with cadherins whose mutation is linked to autism, and GRIP, an AMPA receptor (AMPAR) scaffolding protein, and the AMPAR subunit, GluA2. We show that Li(+) elevates the level of δ-catenin in cultured neurons. δ-catenin binds to the ABP and GRIP proteins, which are synaptic scaffolds for GluA2...
October 25, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27781960/angiotensin-mediated-oxidative-stress-and-neuroprotective-potential-of-antioxidants-and-at1-receptor-blockers
#13
Bharat Bhusan Subudhi, Pratap Kumar Sahu
Oxidative stress in brain underlies the major neurological disorders including Alzheimer's disease (AD) and Parkinson's disease (PD). Peripherally, Angiotensin-II is a major effector of inflammation. Identification of its capacity to access brain during hypertension, as well as location of central rennin angiotensin system have led to its recognition as the major effector of oxidative stress in brain. Clinical uses of antioxidants to antagonize this oxidative stress have mostly failed. In this scenario, AT1 blockers have been investigated to prevent neurodegeneration...
October 24, 2016: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/27777941/a-review-of-rett-syndrome-rtt-with-induced-pluripotent-stem-cells
#14
Vellingiri Balachandar, Venkatesan Dhivya, Mohan Gomathi, Subramaniam Mohanadevi, Balasubramanian Venkatesh, Bharathi Geetha
Human induced pluripotent stem cells (hiPSCs) are pluripotent stem cells generated from somatic cells by the introduction of a combination of pluripotency-associated genes such as OCT4, SOX2, along with either KLF4 and c-MYC or NANOG and LIN28 via retroviral or lentiviral vectors. Most importantly, hiPSCs are similar to human embryonic stem cells (hESCs) functionally as they are pluripotent and can potentially differentiate into any desired cell type when provided with the appropriate cues, but do not have the ethical issues surrounding hESCs...
2016: Stem Cell Investigation
https://www.readbyqxmd.com/read/27771379/novel-highly-potent-and-in%C3%A2-vivo-active-inhibitor-of-gaba-transporter-subtype-1-with-anticonvulsant-anxiolytic-antidepressant-and-antinociceptive-properties
#15
Kinga Sałat, Adrian Podkowa, Natalia Malikowska, Felix Kern, Jörg Pabel, Ewelina Wojcieszak, Katarzyna Kulig, Klaus T Wanner, Beata Strach, Elżbieta Wyska
BACKGROUND AND PURPOSE: Since GABAergic dysfunction underlies a variety of neurological and psychiatric disorders, numerous strategies leading to the augmentation of GABAergic neurotransmission have been introduced. One of them is the inhibition of GABA reuptake from the synaptic cleft mediated by four plasma membrane GABA transporters (GAT1-4). GAT1 which is exclusively expressed in the brain is an interesting target for centrally acting drugs. In this research, pharmacological properties of a novel, highly potent and selective inhibitor of GAT1, the guvacine derivative named DDPM-2571, were assessed in vivo...
October 19, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27755933/psychoradiology-the-frontier-of-neuroimaging-in-psychiatry
#16
Su Lui, Xiaohong Joe Zhou, John A Sweeney, Qiyong Gong
Unlike neurologic conditions, such as brain tumors, dementia, and stroke, the neural mechanisms for all psychiatric disorders remain unclear. A large body of research obtained with structural and functional magnetic resonance imaging, positron emission tomography/single photon emission computed tomography, and optical imaging has demonstrated regional and illness-specific brain changes at the onset of psychiatric disorders and in individuals at risk for such disorders. Many studies have shown that psychiatric medications induce specific measurable changes in brain anatomy and function that are related to clinical outcomes...
November 2016: Radiology
https://www.readbyqxmd.com/read/27739621/african-trypanosomes-and-brain-infection%C3%A2-%C3%A2-the-unsolved-question
#17
Stefan Mogk, Christian M Boßelmann, Celestin N Mudogo, Jasmin Stein, Hartwig Wolburg, Michael Duszenko
African trypanosomes induce sleeping sickness. The parasites are transmitted during the blood meal of a tsetse fly and appear primarily in blood and lymph vessels, before they enter the central nervous system. During the latter stage, trypanosomes induce a deregulation of sleep-wake cycles and some additional neurological disorders. Historically, it was assumed that trypanosomes cross the blood-brain barrier and settle somewhere between the brain cells. The brain, however, is a strictly controlled and immune-privileged area that is completely surrounded by a dense barrier that covers the blood vessels: this is the blood-brain barrier...
October 14, 2016: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/27729249/galacto-n-biose-is-neuroprotective-against-glutamate-induced-excitotoxicity-in-vitro
#18
Yo Shinoda, Yui Nakajima, Hirotoshi Iguchi, Satoshi Tatsumi, Motomitsu Kitaoka, Masahiro Nakajima, Tsutomu Takahashi, Yasuyuki Fujiwara, Teiichi Furuichi
Galacto-N-biose (GNB: Galβ1-3GalNAc) is an O-glycan disaccharide core moiety that is a core component of mucin in the gastrointestinal tract; however, the physiological properties of GNB are not well understood. Glutamate excitotoxicity causes neuronal death in acute neurological disorders including stroke, trauma, and neurodegenerative disease. Therefore the discovery of drugs to treat glutamate excitotoxicity is an important goal. Here, we report that GNB is neuroprotective against glutamate-induced excitotoxicity...
October 8, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27725795/astrocyte-differentiation-of-human-pluripotent-stem-cells-new-tools-for-neurological-disorder-research
#19
Abinaya Chandrasekaran, Hasan X Avci, Marcel Leist, Julianna Kobolák, Andras Dinnyés
Astrocytes have a central role in brain development and function, and so have gained increasing attention over the past two decades. Consequently, our knowledge about their origin, differentiation and function has increased significantly, with new research showing that astrocytes cultured alone or co-cultured with neurons have the potential to improve our understanding of various central nervous system diseases, such as amyotrophic lateral sclerosis, Alzheimer's disease, or Alexander disease. The generation of astrocytes derived from pluripotent stem cells (PSCs) opens up a new area for studying neurologic diseases in vitro; these models could be exploited to identify and validate potential drugs by detecting adverse effects in the early stages of drug development...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27719874/nature-of-the-placebo-and-nocebo-effect-in-relation-to-functional-neurologic-disorders
#20
E Carlino, A Piedimonte, F Benedetti
Placebos have long been considered a nuisance in clinical research, for they have always been used as comparators for the validation of new treatments. By contrast, today they represent an active field of research, and, due to the involvement of many mechanisms, the study of the placebo effect can actually be viewed as a melting pot of concepts and ideas for neuroscience. There is not a single placebo effect, but many, with different mechanisms across different medical conditions and therapeutic interventions...
2017: Handbook of Clinical Neurology
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