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CNS Drugs

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https://www.readbyqxmd.com/read/27914038/serotonin-5-ht6-receptor-antagonists-in-alzheimer-s-disease-therapeutic-rationale-and-current-development-status
#1
Hilda Ferrero, Maite Solas, Paul T Francis, Maria J Ramirez
Alzheimer's disease (AD) is the most common cause of dementia in elderly people. Because of the lack of effective treatments for this illness, research focused on identifying compounds that restore cognition and functional impairments in patients with AD is a very active field. Since its discovery in 1993, the serotonin 5-HT6 receptor has received increasing attention, and a growing number of studies supported 5-HT6 receptor antagonism as a target for improving cognitive dysfunction in AD. This article reviews the rationale behind investigations into the targeting of 5-HT6 receptors as a symptomatic treatment for cognitive and/or behavioral symptoms of AD...
December 3, 2016: CNS Drugs
https://www.readbyqxmd.com/read/27896706/anesthetics-and-outcome-in-status-epilepticus-a-matched-two-center-cohort-study
#2
Raoul Sutter, Gian Marco De Marchis, Saskia Semmlack, Peter Fuhr, Stephan Rüegg, Stephan Marsch, Wendy C Ziai, Peter W Kaplan
BACKGROUND: The use of anesthetics has been linked to poor outcome in patients with status epilepticus (SE). This association, however, may be confounded, as anesthetics are mostly administered in patients with more severe SE and critical illnesses. OBJECTIVE: To minimize treatment-selection bias, we assessed the association between continuously administered intravenous anesthetic drugs (IVADs) and outcome in SE patients by a matched two-center study design. METHODS: This cohort study was performed at the Johns Hopkins Bayview Medical Center, Baltimore, MD, USA and the University Hospital Basel, Basel, Switzerland...
November 29, 2016: CNS Drugs
https://www.readbyqxmd.com/read/27882532/alemtuzumab-use-in-clinical-practice-recommendations-from-european-multiple-sclerosis-experts
#3
Thomas Berger, Irina Elovaara, Sten Fredrikson, Chris McGuigan, Lucia Moiola, Kjell-Morten Myhr, Celia Oreja-Guevara, Igor Stoliarov, Uwe K Zettl
Alemtuzumab (Lemtrada™) is a humanized monoclonal antibody approved in more than 50 countries. Within the European Union, alemtuzumab is indicated for the treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS) with active disease defined by clinical or imaging features; in the USA, the indication states that alemtuzumab should generally be reserved for the treatment of patients with relapsing forms of multiple sclerosis who have had an inadequate response to two or more disease-modifying therapies (DMTs)...
November 23, 2016: CNS Drugs
https://www.readbyqxmd.com/read/27878767/phenobarbital-versus-valproate-for-generalized-convulsive-status-epilepticus-in-adults-a-prospective-randomized-controlled-trial-in-china
#4
Yingying Su, Gang Liu, Fei Tian, Guoping Ren, Mengdi Jiang, Brian Chun, Yunzhou Zhang, Yan Zhang, Hong Ye, Daiquan Gao, Weibi Chen
OBJECTIVE: Although generalized convulsive status epilepticus (GCSE) is a life-threatening emergency, evidence-based data to guide initial drug treatment choices are lacking in the Chinese population. We conducted this prospective, randomized, controlled trial to evaluate the relative efficacy and safety of intravenous phenobarbital and valproate in patients with GCSE. METHODS: After the failure of first-line diazepam treatment, Chinese adult patients with GCSE were randomized to receive either intravenous phenobarbital (standard doses, low rate) or valproate (standard)...
November 23, 2016: CNS Drugs
https://www.readbyqxmd.com/read/27878559/impact-of-drug-manipulation-on-seizure-freedom-in-adults-with-uncontrolled-epilepsy-a-prospective-controlled-study-in-rural-china
#5
Xiaoting Hao, Ziyi Chen, Bo Yan, Patrick Kwan, Dong Zhou
INTRODUCTION: It has been suggested that uncontrolled epilepsy might not necessarily equate to drug resistance when antiepileptic drugs (AEDs) are used at relatively low doses, a practice frequently observed in rural areas of China. OBJECTIVE: To assess the clinical benefits of further drug manipulation in this situation, we prospectively followed up the outcomes of patients with uncontrolled epilepsy while taking relatively low doses of AEDs. METHODS: The study included patients aged 16 years and older with uncontrolled epilepsy and who were receiving at least one AED at a dosage below 50% of the World Health Organization (WHO) defined daily dose (DDD) (50% DDD) (Group 1)...
November 22, 2016: CNS Drugs
https://www.readbyqxmd.com/read/27873224/therapeutic-potential-of-transdermal-glyceryl-trinitrate-in-the-management-of-acute-stroke
#6
Jason P Appleton, Nikola Sprigg, Philip M Bath
The nitric oxide donor, glyceryl trinitrate (GTN), is a candidate treatment for the management of acute stroke with haemodynamic and potential reperfusion and neuroprotective effects. When administered as a transdermal patch during the acute and subacute phases after stroke, GTN was safe, lowered blood pressure, maintained cerebral blood flow, and did not induce cerebral steal or alter functional outcome. However, when given within 6 h of stroke onset, GTN reduced death and dependency (odds ratio 0.52; 95% confidence interval 0...
November 21, 2016: CNS Drugs
https://www.readbyqxmd.com/read/27848217/pregabalin-for-the-treatment-of-drug-and-alcohol-withdrawal-symptoms-a-comprehensive-review
#7
REVIEW
Rainer Freynhagen, Miroslav Backonja, Stephan Schug, Gavin Lyndon, Bruce Parsons, Stephen Watt, Regina Behar
Treatments for physical dependence and associated withdrawal symptoms following the abrupt discontinuation of prescription drugs (such as opioids and benzodiazepines), nicotine, alcohol, and cannabinoids are available, but there is still a need for new and more effective therapies. This review examines evidence supporting the potential use of pregabalin, an α2δ voltage-gated calcium channel subunit ligand, for the treatment of physical dependence and associated withdrawal symptoms. A literature search of the MEDLINE and Cochrane Library databases up to and including 11 December 2015 was conducted...
November 16, 2016: CNS Drugs
https://www.readbyqxmd.com/read/27832476/neurological-and-neuropsychiatric-adverse-effects-of-dermatologic-medications
#8
REVIEW
Melinda Liu, Yuan Yu M Huang, Sylvia Hsu, Joseph S Kass
Severe, recalcitrant dermatologic conditions often require systemic treatment. Although efficacious, these medications have been associated with wide-ranging adverse reactions. Some are reversible, predictable, and either dose-dependent or treatment length-dependent, while others are unpredictable, irreversible, and potentially fatal. This review examines the neuropsychiatric adverse effects associated with US FDA-approved medications for treatment of the following dermatologic pathologies that typically require systemic therapy: autoimmune dermatoses, acne, psoriasis, and melanoma...
November 10, 2016: CNS Drugs
https://www.readbyqxmd.com/read/27826741/the-porirua-protocol-in-the-treatment-of-clozapine-induced-gastrointestinal-hypomotility-and-constipation-a-pre-and-post-treatment-study
#9
Susanna Every-Palmer, Pete M Ellis, Mike Nowitz, James Stanley, Eve Grant, Mark Huthwaite, Helen Dunn
BACKGROUND: Clozapine, an antipsychotic used in treatment-resistant schizophrenia, causes slow gastrointestinal transit in 50-80% of patients. Clozapine-induced gastrointestinal hypomotility is both common and serious, and potential complications include severe constipation, ileus, bowel obstruction and related complications, with a higher mortality rate than clozapine-related agranulocytosis. Little evidence exists on its prevention and management. METHOD: Using a well-validated radiopaque marker ('Metcalf') method, we compared colonic transit times (CTTs) of clozapine-treated inpatients not receiving laxatives with their transit times when receiving laxatives, with treatment prescribed according to the Porirua Protocol for clozapine-related constipation (docusate and senna augmented by macrogol 3350 in treatment-resistant cases)...
November 8, 2016: CNS Drugs
https://www.readbyqxmd.com/read/27826740/calcium-channel-antagonists-as-disease-modifying-therapy-for-parkinson-s-disease-therapeutic-rationale-and-current-status
#10
Tara Swart, Michael J Hurley
Parkinson's disease is a disabling hypokinetic neurological movement disorder in which the aetiology is unknown in the majority of cases. Current pharmacological treatments, though effective at restoring movement, are only symptomatic and do nothing to slow disease progression. Electrophysiological, epidemiological and neuropathological studies have implicated CaV1.3 subtype calcium channels in the pathogenesis of the disorder, and drugs with some selectivity for this ion channel (brain-penetrant dihydropyridine calcium channel blockers) are neuroprotective in animal models of the disease...
November 8, 2016: CNS Drugs
https://www.readbyqxmd.com/read/27826739/acknowledgement-to-referees
#11
(no author information available yet)
No abstract text is available yet for this article.
November 8, 2016: CNS Drugs
https://www.readbyqxmd.com/read/27752945/pharmacogenetics-and-imaging-pharmacogenetics-of-antidepressant-response-towards-translational-strategies
#12
Tristram A Lett, Henrik Walter, Eva J Brandl
Genetic variation underlies both the response to antidepressant treatment and the occurrence of side effects. Over the past two decades, a number of pharmacogenetic variants, among these the SCL6A4, BDNF, FKBP5, GNB3, GRIK4, and ABCB1 genes, have come to the forefront in this regard. However, small effects sizes, mixed results in independent samples, and conflicting meta-analyses results led to inherent difficulties in the field of pharmacogenetics translating these findings into clinical practice. Nearly all antidepressant pharmacogenetic variants have potentially pleiotropic effects in which they are associated with major depressive disorder, intermediate phenotypes involved in emotional processes, and brain areas affected by antidepressant treatment...
October 17, 2016: CNS Drugs
https://www.readbyqxmd.com/read/27752944/synaptic-vesicle-glycoprotein-2a-ligands-in-the-treatment-of-epilepsy-and-beyond
#13
Wolfgang Löscher, Michel Gillard, Zara A Sands, Rafal M Kaminski, Henrik Klitgaard
The synaptic vesicle glycoprotein SV2A belongs to the major facilitator superfamily (MFS) of transporters and is an integral constituent of synaptic vesicle membranes. SV2A has been demonstrated to be involved in vesicle trafficking and exocytosis, processes crucial for neurotransmission. The anti-seizure drug levetiracetam was the first ligand to target SV2A and displays a broad spectrum of anti-seizure activity in various preclinical models. Several lines of preclinical and clinical evidence, including genetics and protein expression changes, support an important role of SV2A in epilepsy pathophysiology...
October 17, 2016: CNS Drugs
https://www.readbyqxmd.com/read/27743318/novel-levodopa-formulations-for-parkinson-s-disease
#14
Maria Eliza Freitas, Marta Ruiz-Lopez, Susan H Fox
Levodopa remains the most effective treatment for Parkinson's disease and is considered the gold standard therapy. However, disease progression and changes in the gastrointestinal tract result in a declining window of treatment response in a majority of patients. Efforts have been made recently to improve levodopa bioavailability either by developing more effective oral formulations or by innovating routes of administration (intestinal infusion, transcutaneous or inhaled levodopa). IPX066 is a novel levodopa-carbidopa (LD/CD) oral formulation combining immediate-release (IR) and extended-release (ER) LD/CD recently approved in the USA and the EU...
October 14, 2016: CNS Drugs
https://www.readbyqxmd.com/read/27844213/b-cell-directed-therapeutics-in-multiple-sclerosis-rationale-and-clinical-evidence
#15
REVIEW
Silke Kinzel, Martin S Weber
Over the last decade, evidence condensed that B cells, B cell-derived plasma cells and antibodies play a key role in the pathogenesis and progression of multiple sclerosis (MS). In many patients with MS, peripheral B cells show signs of chronic activation; within the cerebrospinal fluid clonally expanded plasma cells produce oligoclonal immunoglobulins, which remain a hallmark diagnostic finding. Confirming the clinical relevance of these immunological alterations, recent trials testing anti-CD20-mediated depletion of peripheral B cells showed an instantaneous halt in development of new central nervous system lesions and occurrence of relapses...
December 2016: CNS Drugs
https://www.readbyqxmd.com/read/27623676/clinical-drug-development-in-epilepsy-revisited-a-proposal-for-a-new-paradigm-streamlined-using-extrapolation
#16
Ian Wadsworth, Thomas Jaki, Graeme J Sills, Richard Appleton, J Helen Cross, Anthony G Marson, Tim Martland, Ailsa McLellan, Philip E M Smith, John M Pellock, Lisa V Hampson
Data from clinical trials in adults, extrapolated to predict benefits in paediatric patients, could result in fewer or smaller trials being required to obtain a new drug licence for paediatrics. This article outlines the place of such extrapolation in the development of drugs for use in paediatric epilepsies. Based on consensus expert opinion, a proposal is presented for a new paradigm for the clinical development of drugs for focal epilepsies. Phase I data should continue to be collected in adults, and phase II and III trials should simultaneously recruit adults and paediatric patients aged above 2 years...
November 2016: CNS Drugs
https://www.readbyqxmd.com/read/27638546/therapeutic-mechanisms-of-lithium-in-bipolar-disorder-recent-advances-and-current-understanding
#17
REVIEW
Gin S Malhi, Tim Outhred
Lithium is the most effective and well established treatment for bipolar disorder, and it has a broad array of effects within cellular pathways. However, the specific processes through which therapeutic effects occur and are maintained in bipolar disorder remain unclear. This paper provides a timely update to an authoritative review of pertinent findings that was published in CNS Drugs in 2013. A literature search was conducted using the Scopus database, and was limited by year (from 2012). There has been a resurgence of interest in lithium therapy mechanisms, perhaps driven by technical advancements in recent years that permit the examination of cellular mechanisms underpinning the effects of lithium-along with the reuptake of lithium in clinical practice...
October 2016: CNS Drugs
https://www.readbyqxmd.com/read/27541607/comment-on-levodopa-carbidopa-intestinal-gel-in-patients-with-parkinson-s-disease-a-systematic-review
#18
LETTER
Andrew T Lambarth
No abstract text is available yet for this article.
October 2016: CNS Drugs
https://www.readbyqxmd.com/read/27541606/authors-reply-to-lambarth-levodopa-carbidopa-intestinal-gel-in-patients-with-parkinson-s-disease-a-systematic-review
#19
LETTER
Karin Wirdefeldt, Per Odin, Dag Nyholm
No abstract text is available yet for this article.
October 2016: CNS Drugs
https://www.readbyqxmd.com/read/27538416/benefit-risk-of-therapies-for-relapsing-remitting-multiple-sclerosis-testing-the-number-needed-to-treat-to-benefit-nntb-number-needed-to-treat-to-harm-nnth-and-the-likelihood-to-be-helped-or-harmed-lhh-a-systematic-review-and-meta-analysis
#20
REVIEW
Diogo Mendes, Carlos Alves, Francisco Batel-Marques
OBJECTIVE: This study aimed to test the number needed to treat to benefit (NNTB) and to harm (NNTH), and the likelihood to be helped or harmed (LHH) when assessing benefits, risks, and benefit-risk ratios of disease-modifying treatments (DMTs) approved for relapsing-remitting multiple sclerosis (RRMS). METHODS: In May 2016, we conducted a systematic review using the PubMed and Cochrane Central Register of Controlled Trials databases to identify phase III, randomized controlled trials with a duration of ≥2 years that assessed first-line (dimethyl fumarate [DMF], glatiramer acetate [GA], β-interferons [IFN], and teriflunomide) or second-line (alemtuzumab, fingolimod, and natalizumab) DMTs in patients with RRMS...
October 2016: CNS Drugs
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