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Drug induced neurological disorders

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https://www.readbyqxmd.com/read/28098253/the-clinically-approved-antiviral-drug-sofosbuvir-inhibits-zika-virus-replication
#1
Carolina Q Sacramento, Gabrielle R de Melo, Caroline S de Freitas, Natasha Rocha, Lucas Villas Bôas Hoelz, Milene Miranda, Natalia Fintelman-Rodrigues, Andressa Marttorelli, André C Ferreira, Giselle Barbosa-Lima, Juliana L Abrantes, Yasmine Rangel Vieira, Mônica M Bastos, Eduardo de Mello Volotão, Estevão Portela Nunes, Diogo A Tschoeke, Luciana Leomil, Erick Correia Loiola, Pablo Trindade, Stevens K Rehen, Fernando A Bozza, Patrícia T Bozza, Nubia Boechat, Fabiano L Thompson, Ana M B de Filippis, Karin Brüning, Thiago Moreno L Souza
Zika virus (ZIKV) is a member of the Flaviviridae family, along with other agents of clinical significance such as dengue (DENV) and hepatitis C (HCV) viruses. Since ZIKV causes neurological disorders during fetal development and in adulthood, antiviral drugs are necessary. Sofosbuvir is clinically approved for use against HCV and targets the protein that is most conserved among the members of the Flaviviridae family, the viral RNA polymerase. Indeed, we found that sofosbuvir inhibits ZIKV RNA polymerase, targeting conserved amino acid residues...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28096470/dampened-amphetamine-stimulated-behavior-and-altered-dopamine-transporter-function-in-the-absence-of-brain-gdnf
#2
Jaakko Kopra, Anne Panhelainen, Sara Af Bjerkén, Lauriina Porokuokka, Kärt Varendi, Soophie Olfat, Heidi Montonen, T Petteri Piepponen, Mart Saarma, Jaan-Olle Andressoo
: Midbrain dopamine neuron dysfunction contributes to various psychiatric and neurological diseases including drug addiction and Parkinson's disease. Because of its well-established dopaminotrophic effects, the therapeutic potential of glial cell line-derived neurotrophic factor (GDNF) has been extensively studied in various disorders with disturbed dopamine homeostasis. The outcomes from pre-clinical and clinical studies vary, however, highlighting a need for a better understanding of the physiological role of GDNF on striatal dopaminergic function...
January 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28066149/neuroprotective-effect-of-lithium-after-pilocarpine-induced-status-epilepticus-in-mice
#3
Namgue Hong, Yun-Sik Choi, Seong Yun Kim, Hee Jung Kim
Status epilepticus is the most common serious neurological condition triggered by abnormal electrical activity, leading to severe and widespread cell loss in the brain. Lithium has been one of the main drugs used for the treatment of bipolar disorder for decades, and its anticonvulsant and neuroprotective properties have been described in several neurological disease models. However, the therapeutic mechanisms underlying lithium's actions remain poorly understood. The muscarinic receptor agonist pilocarpine is used to induce status epilepticus, which is followed by hippocampal damage...
January 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28030918/to-treat-or-not-to-treat-drug-refractory-epilepsy-by-the-ketogenic-diet-that-is-the-question
#4
REVIEW
Marzena Ułamek-Kozioł, Ryszard Pluta, Anna Bogucka-Kocka, Stanisław J Czuczwar
Epilepsy is a serious neurologic disorder worldwide which affects about 1% of the population (ca. 50 million people), the highest prevalence occurring in both children and elderly. Apart from idiopathic forms, etiology of the disease involves multiple brain risk factors - the most frequent being cerebrovascular diseases, tumours and traumatic injuries. Several treatment options exist, including, for instance, pharmacotherapy, vagal nerve stimulation or epilepsy surgery. In spite of treatment, about 30% of patients with epilepsy still have seizures and become drug-refractory...
23, 2016: Annals of Agricultural and Environmental Medicine: AAEM
https://www.readbyqxmd.com/read/28012058/glutamate-and-brain-glutaminases-in-drug-addiction
#5
Javier Márquez, José A Campos-Sandoval, Ana Peñalver, José M Matés, Juan A Segura, Eduardo Blanco, Francisco J Alonso, Fernando Rodríguez de Fonseca
Glutamate is the principal excitatory neurotransmitter in the central nervous system and its actions are related to the behavioral effects of psychostimulant drugs. In the last two decades, basic neuroscience research and preclinical studies with animal models are suggesting a critical role for glutamate transmission in drug reward, reinforcement, and relapse. Although most of the interest has been centered in post-synaptic glutamate receptors, the presynaptic synthesis of glutamate through brain glutaminases may also contribute to imbalances in glutamate homeostasis, a key feature of the glutamatergic hypothesis of addiction...
December 23, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27932945/monoaminergic-and-histaminergic-strategies-and-treatments-in-brain-diseases
#6
REVIEW
Giuseppe Di Giovanni, Dubravka Svob Strac, Montse Sole, Mercedes Unzeta, Keith F Tipton, Dorotea Mück-Šeler, Irene Bolea, Laura Della Corte, Matea Nikolac Perkovic, Nela Pivac, Ilse J Smolders, Anna Stasiak, Wieslawa A Fogel, Philippe De Deurwaerdère
The monoaminergic systems are the target of several drugs for the treatment of mood, motor and cognitive disorders as well as neurological conditions. In most cases, advances have occurred through serendipity, except for Parkinson's disease where the pathophysiology led almost immediately to the introduction of dopamine restoring agents. Extensive neuropharmacological studies first showed that the primary target of antipsychotics, antidepressants, and anxiolytic drugs were specific components of the monoaminergic systems...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27931886/neurobiological-after-effects-of-non-invasive-brain-stimulation
#7
REVIEW
G Cirillo, G Di Pino, F Capone, F Ranieri, L Florio, V Todisco, G Tedeschi, K Funke, V Di Lazzaro
BACKGROUND: In recent years, many studies have evaluated the effects of noninvasive brain stimulation (NIBS) techniques for the treatment of several neurological and psychiatric disorders. Positive results led to approval of NIBS for some of these conditions by the Food and Drug Administration in the USA. The therapeutic effects of NIBS have been related to bi-directional changes in cortical excitability with the direction of change depending on the choice of stimulation protocol. Although after-effects are mostly short lived, complex neurobiological mechanisms related to changes in synaptic excitability bear the potential to further induce therapy-relevant lasting changes...
November 17, 2016: Brain Stimulation
https://www.readbyqxmd.com/read/27927955/gpr126-adgrg6-has-schwann-cell-autonomous-and-nonautonomous-functions-in-peripheral-nerve-injury-and-repair
#8
Amit Mogha, Breanne L Harty, Dan Carlin, Jessica Joseph, Nicholas E Sanchez, Ueli Suter, Xianhua Piao, Valeria Cavalli, Kelly R Monk
: Schwann cells (SCs) are essential for proper peripheral nerve development and repair, although the mechanisms regulating these processes are incompletely understood. We previously showed that the adhesion G protein-coupled receptor Gpr126/Adgrg6 is essential for SC development and myelination. Interestingly, the expression of Gpr126 is maintained in adult SCs, suggestive of a function in the mature nerve. We therefore investigated the role of Gpr126 in nerve repair by studying an inducible SC-specific Gpr126 knock-out mouse model...
December 7, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27917413/efficacy-of-s-lacosamide-in-preclinical-models-of-cephalic-pain
#9
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
#10
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
#11
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...
January 2017: 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
#12
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
#13
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 have 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...
February 2017: 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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...
February 2017: Neuropharmacology
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