DOCSLIB.ORG

1 Effects of Transdermal Nicotine on Response Inhibition to Emotional

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
1 Effects of Transdermal Nicotine on Response Inhibition to Emotional Official title of study: Effects of transdermal nicotine on response inhibition to emotional cues in schizophrenia NCT number: NCT03838484 Date of document: 10/23/2019 1 Effects of transdermal nicotine on response inhibition to emotional cues in schizophrenia Protocol short title: Nicotine and response inhibition Protocol Number: 190021 Alan Lewis, M.D., Ph.D. Department of Psychiatry and Behavioral Sciences Vanderbilt University Medical Center 465 21st Avenue S. MRBIII, Room 6140B, Nashville, TN, 37240 2 Table of Contents: 1 Background ............................................................................................................. 4 2 Rationale and specific aims .................................................................................... 4 3 Animal studies and previous human studies ........................................................ 6 3.1 Animal studies .................................................................................................... 6 3.2 Human studies .................................................................................................... 6 4 Inclusion/exclusion criteria .................................................................................... 7 4.1 Inclusion criteria for schizophrenia subjects ........................................................ 7 4.2 Exclusion criteria for schizophrenia subjects ....................................................... 8 4.3 Inclusion criteria for healthy controls ................................................................... 8 4.4 Exclusion criteria for healthy controls .................................................................. 8 5 Enrollment/randomization ...................................................................................... 9 5.1 Subject recruitment and enrollment .................................................................... 9 5.2 Process of consent ............................................................................................. 9 5.3 Evaluation of subject capacity to provide informed consent .............................. 10 5.4 Randomization.................................................................................................. 10 6 Study Procedures .................................................................................................. 10 6.1 Baseline: day 0 ................................................................................................. 10 6.2 Testing: days 1 and 2 ....................................................................................... 11 7 Study drug ............................................................................................................. 12 7.1 Background ...................................................................................................... 13 7.2 Drug source ...................................................................................................... 13 7.3 Storage, preparation and use ........................................................................... 13 7.4 Justification for the use of placebo .................................................................... 13 8 Risks, minimizing risks, and potential benefits .................................................. 13 8.1 Risks ................................................................................................................ 13 8.1.1 Study medication: transdermal nicotine...................................................... 13 8.1.2 Psychological assessments and Emotional Go/NoGo task ........................ 14 8.1.3 Electroencephalography (EEG) ................................................................. 15 8.2 Minimizing Risks ............................................................................................... 15 8.2.1 Risk of study medication ............................................................................ 15 8.2.2 Risk of psychological assessments and Emotional Go/NoGo task ............. 15 8.2.3 Electroencephalography (EEG) ................................................................. 15 8.2.4 Risk of breach of data security and privacy ................................................ 15 8.2.5 Subject Monitoring and Emergency Procedures ........................................ 16 8.3 Potential benefits .............................................................................................. 16 9 Research alternatives and economic considerations ......................................... 16 9.1 Alternatives to participation in the study ............................................................ 16 9.2 Payments for participation ................................................................................ 16 9.3 Costs for participation ....................................................................................... 17 9.4 Medical treatment in case of injury .................................................................... 17 10 Reporting of adverse events or unanticipated problems involving risk to participants or others ................................................................................................. 17 10.1 Greater than minimal risk Data and Safety Monitoring Plan ............................ 17 10.1.1 Personnel responsible for the safety review and its frequency ................. 18 10.1.2 Attribution of adverse events .................................................................... 18 10.1.3 Plan for grading adverse events............................................................... 18 10.1.4 Plan for determining seriousness of adverse events ................................ 18 10.1.5 Plan for reporting Unanticipated Problems Involving Risks to Subjects or Others (UPIRSOs, including Adverse Events) to the IRB ....................................... 19 3 10.1.6 Plan for reporting adverse events to co-investigators on the study, DSMBs, study sponsors, funding and regulatory agencies, and regulatory and decision- making bodies. ...................................................................................................... 19 11 Study withdrawal/discontinuation ...................................................................... 20 12 Statistical considerations ................................................................................... 20 12.1 Power analysis ............................................................................................... 20 12.2 Data analysis plan .......................................................................................... 21 12.3 Inclusion of men and women .......................................................................... 21 13 Privacy/confidentiality issues............................................................................. 21 14 Follow-up and record retention .......................................................................... 21 4 1 Background Aggressive behavior can be largely divided into either instrumental aggression, which is purposeful aggression to obtain a desired outcome, or impulsive aggression, which is sudden, inappropriate aggression mounted in the context of strong emotion such as anger or frustration.1 Impulsive aggression frequently complicates severe neuropsychiatric disorders occurring across the lifespan, worsens outcomes,2 and isolates patients from their communities. Management of persistent impulsive aggression is an unmet challenge for diverse healthcare settings such as residential and nursing treatment facilities, civil and forensic psychiatric hospitals, and criminal justice settings.3, 4 For example, while the majority of people with schizophrenia spectrum disorders are not violent, such conditions confer an aggregate increased risk of violence and aggression,5-7 with more than half of patients in forensic psychiatric settings diagnosed with schizophrenia.8 In recent decades, such patients have increasingly been institutionalized in prisons and jails9 at a cost of more than $14 billion,10 yet still receive substandard care11 and have high rates of reincarceration.10 Vast expenditures to treat aggression also occur in non-correctional settings. For example, one-third of the total $236 billion cost to treat Alzheimer’s disease in the U.S. is spent to manage behavioral and psychological symptoms, including aggression.12, 13 Current treatment approaches for aggression in neuropsychiatric disorders incorporate environmental, behavioral, and pharmacological interventions,4 yet aggressive behaviors commonly remain treatment- resistant.3, 14-16 For these patients, psychopharmacological agents with diverse pharmacological actions are trialed off-label, despite limited pathophysiological rationale, inconsistent clinical benefit,5, 17 and increased morbidity or mortality.18 To address this growing need with important individual and societal implications, novel therapeutic approaches must be designed based on an increased understanding of the neural circuits governing aggressive behavior. 2 Rationale and specific aims This human laboratory study seeks to test the hypothesis that activation of nicotinic acetylcholine receptors (nAChRs) in the brain will reduce impulsive behavior in response to negative emotional cues as compared to neutral emotional cues. Because impulsive action during negative mood states is strongly correlated with impulsive aggression in both healthy individuals and individuals with schizophrenia (discussed below), our overarching, long-term goal is to determine whether nAChRs in general
Load more

Recommended publications
  • Role of Prefrontal Cortex and Cholinergic Modulation in Attentional
    Role of prefrontal cortex and cholinergic modulation in attentional performance in rats Beth Mary Fisher Department of Psychology Downing College University of Cambridge September 2017 This dissertation is submitted for the degree of Doctor of Philosophy Declaration This dissertation is the result of my own work and includes nothing which is the outcome of work done in collaboration except as declared in the Preface and specified in the text. It is not substantially the same as any that I have submitted, or, is being concurrently submitted for a degree or diploma or other qualification at the University of Cambridge or any other University or similar institution except as declared in the Preface and specified in the text. I further state that no substantial part of my dissertation has already been submitted, or, is being concurrently submitted for any such degree, diploma or other qualification at the University of Cambridge or any other University or similar institution except as declared in the Preface and specified in the text. It does not exceed the prescribed word limit of the degree committee for the faculty of biology of 60,000 words. i2 Acknowledgements Firstly, I would like to thank my supervisor Tim Bussey and advisor Trevor Robbins for their invaluable support, guidance and encouragement throughout my PhD. Their insightful scientific discussions, passion for the field and praise of me, have shaped me to become a scientist I am proud of, and given me an unknown confidence. Not only are they experts in the field, but they are down to earth, kind and fun.
    [Show full text]
  • Hayward Et Al, 2017
    European Neuropsychopharmacology (]]]]) ], ]]]–]]] www.elsevier.com/locate/euroneuro Partial agonism at the α7 nicotinic acetylcholine receptor improves attention, impulsive action and vigilance in low attentive rats Andrew Haywardn, Lisa Adamson, Joanna C. Neilln Division of Pharmacy and Optometry, School of Health Sciences, University of Manchester, Manchester M13 9PT, UK Received 7 July 2016; received in revised form 9 January 2017; accepted 18 January 2017 KEYWORDS Abstract 5 choice-continuous Inattention is a disabling symptom in conditions such as schizophrenia and attention deficit/ performance task; hyperactivity disorder. Nicotine can improve attention and vigilance, but is unsuitable for clinical use 5C-CPT; due to abuse liability. Genetic knockout of the α7 nicotinic acetylcholine receptor (nAChR) induces α 7 nAChR; attention deficits therefore selective agonism may improve attention, without the abuse liability Animal Model; associated with nicotine. The α7 nAChR partial agonist encenicline (formerly EVP-6124) enhances Behavioural separa- memory in rodents and humans. Here we investigate, for the first time, efficacy of encenicline to tion; Low attentive improve attention and vigilance in animals behaviourally grouped for low attentive traits in the 5 choice-continuous performance task (5C-CPT). Female Lister Hooded rats were trained to perform the5C-CPTwithavariablestimulusduration(SD).Animalswerethengroupedbasedonperformance intoupperandlowerquartilesofd0 (vigilance) and accuracy (selective attention), producing high- attentive (HA) and low-attentive (LA) groups. LA animals showed an increase in selective attention and vigilance at 0.3 mg/kg encenicline, a reduction in impulsive action (probability of false alarms) and increase in vigilance following 1 mg/kg at 0.75 s SD. At 1 mg/kg, HA animals had reduced selective attention at 0.75 s SD and reduced vigilance at 0.75 and 1.25 s SD.
    [Show full text]
  • (Tert- Butoxycarbonyl)Amino](3 361442- 3
    Alternative Name CAS 1. Product Name Use Number 320345- 2. Aclidinium bromide API 99-1 (2S)-[(tert- Butoxycarbonyl)amino](3 361442- 3. Saxagliptin int -hydroxyadamant-1- 00-4 yl)ethanoic acid 1,3- 1,3- 5001-18- 4. Dihydroxyadamantane Adamantanediol 3 1,3-Dimethyladamantane 702-79-4 memantine intermediate 5. 1-Acetylamido-3,5- 19982- 6. Memantine int dimethyladamantane 07-1 1- 7. 880-52-4 Acetylaminoadamantane 1- 4942-47- 8. 1-Adamantaneacetic acid Adamantylacetic 6 acid [2-(1- 6240-11- 9. 1-Adamantaneethanol Adamantylethano 5 l)] 1- 10. 1-Adamantanemethanol Adamantylmetha 770-71-8 nol 1- 1660-04- 1-Adamantyl methyl rimantadine intermediate; 11. Acetyladamantan 4 ketone e 1-Chloro-3,5- 707-36-8 memantine intermediate; 12. dimethyladamantane 1-Hydroxy-3,5- memantine intermediate; 13. 707-37-9 dimethyladamantane 2- 14. 2-Adamantanol Hydroxyadamant 700-57-2 ane 15. 2-Adamantanone 700-58-3 2-Aminoadamantane 10523- 16. hydrochloride 68-9 3-Amino-1-hydroxy- 3-Amino-1- 702-82-9 vildagliptin intermediate; 17. adamantane adamantanol 3- 38584- 18. (Hydroxymethyl)adamant 37-1 -1-ol 19. 3-aminomethyl- 865887- mequitazine intermediate; 20. quinuclidine 14-5 dihydrochloride zacopride intermediate; 6530-09- mezacopride intermediate; 3-Aminoquinuclidine 21. 2 pancopride intermediate; dihydrochloride azasetron intermediate; 3-Carbethoxy-dehydro- quifenadine intermediate; 50790- 22. quinuclidine sequifenadine intermediate; 85-7 hydrochloride quifenadine intermediate; 3- 6238-33- 23. sequifenadine intermediate; Carbethoxyquinuclidine 1 3-hydroxymethyl 79221- mequitazine intermediate; 24. quinuclidine 75-3 hydrochloride 3-Quinuclidine 6238-34- 25. carboxylic acid 2 hydrochloride 1619-34- penehyclidine intermediate; 26. 3-Quinuclidinol 7 clidinium intermediate; cevimeline intermediate; 3-Quinuclidinone 1193-65- 27.
    [Show full text]
  • W O 2016/201373 A1 15 December 2016 (15.12.2016) W I PO I P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date W O 2016/201373 A1 15 December 2016 (15.12.2016) W I PO I P C T (51) International Patent Classification: (74) Agents: QUEIROZ DE OLIVEIRA, Pierre et al.; Pepper A61K31/17(2006.01) A61P 25/00 (2006.01) Hamilton LLP, 500 Grant Street, Suite 5000, Pittsburgh, A61K 31/415 (2006.01) PA 15219-2507 (US). (21) International Application Number: (81) Designated States (unless otherwise indicated,for every PCT/US2016/037090 kind of national protection available): AE, AG, AL, AM, .) . AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (22) International Filng Date: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, 10 June 2016 (10.06.2016) DO, DZ, EC, EE, EG, ES, Fl, GB, GD, GE, GH, GM, GT, (25) Filing Language: English HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, (26) Publication Language: English MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (30) Priority Data: PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, 62/174,983 12 June 2015 (12.06.2015) US SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 62/194,084 17 July 2015 (17.07.2015) US TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW.
    [Show full text]
  • The Α7 Nicotinic Agonist ABT-126 in the Treatment
    Neuropsychopharmacology (2016) 41, 2893–2902 © 2016 American College of Neuropsychopharmacology. All rights reserved 0893-133X/16 www.neuropsychopharmacology.org The ɑ7 Nicotinic Agonist ABT-126 in the Treatment of Cognitive Impairment Associated with Schizophrenia in Nonsmokers: Results from a Randomized Controlled Phase 2b Study ,1 1 1,2 1 George Haig* , Deli Wang , Ahmed A Othman and Jun Zhao 1 2 Abbvie Inc., North Chicago, IL, USA; Faculty of Pharmacy, Cairo University, Cairo, Egypt A double-blind, placebo-controlled, parallel-group, 24-week, multicenter trial was conducted to evaluate the efficacy and safety of 3 doses of ABT-126, an α7 nicotinic receptor agonist, for the treatment of cognitive impairment in nonsmoking subjects with schizophrenia. Clinically stable subjects were randomized in 2 stages: placebo, ABT-126 25 mg, 50 mg or 75 mg once daily (stage 1) and placebo or ABT-126 50 mg (stage 2). The primary analysis was the change from baseline to week 12 on the MATRICS Consensus Cognitive Battery (MCCB) neurocognitive composite score for ABT-126 50 mg vs placebo using a mixed-model for repeated-measures. A key secondary measure was the University of California Performance-based Assessment-Extended Range (UPSA-2ER). A total of 432 subjects were randomized and 80% (344/431) completed the study. No statistically significant differences were observed in either the change from baseline for the MCCB neurocognitive composite score (+2.66 [ ± 0.54] for ABT-126 50 mg vs +2.46 [ ± 0.56] for placebo at week 12; P40.05) or the UPSA-2ER. A trend for improvement was seen at week 24 on the 16-item Negative Symptom Assessment Scale total − ± − ± = score for ABT-126 50 mg (change from baseline 4.27 [0.58] vs 3.00 [0.60] for placebo; P 0.059).
    [Show full text]
  • Ion Channels
    UC Davis UC Davis Previously Published Works Title THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels. Permalink https://escholarship.org/uc/item/1442g5hg Journal British journal of pharmacology, 176 Suppl 1(S1) ISSN 0007-1188 Authors Alexander, Stephen PH Mathie, Alistair Peters, John A et al. Publication Date 2019-12-01 DOI 10.1111/bph.14749 License https://creativecommons.org/licenses/by/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: Ion channels. British Journal of Pharmacology (2019) 176, S142–S228 THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels Stephen PH Alexander1 , Alistair Mathie2 ,JohnAPeters3 , Emma L Veale2 , Jörg Striessnig4 , Eamonn Kelly5, Jane F Armstrong6 , Elena Faccenda6 ,SimonDHarding6 ,AdamJPawson6 , Joanna L Sharman6 , Christopher Southan6 , Jamie A Davies6 and CGTP Collaborators 1School of Life Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK 2Medway School of Pharmacy, The Universities of Greenwich and Kent at Medway, Anson Building, Central Avenue, Chatham Maritime, Chatham, Kent, ME4 4TB, UK 3Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK 4Pharmacology and Toxicology, Institute of Pharmacy, University of Innsbruck, A-6020 Innsbruck, Austria 5School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK 6Centre for Discovery Brain Science, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties.
    [Show full text]
  • Nicotinic Acetylcholine Receptors
    nAChR Nicotinic acetylcholine receptors nAChRs (nicotinic acetylcholine receptors) are neuron receptor proteins that signal for muscular contraction upon a chemical stimulus. They are cholinergic receptors that form ligand-gated ion channels in the plasma membranes of certain neurons and on the presynaptic and postsynaptic sides of theneuromuscular junction. Nicotinic acetylcholine receptors are the best-studied of the ionotropic receptors. Like the other type of acetylcholine receptor-the muscarinic acetylcholine receptor (mAChR)-the nAChR is triggered by the binding of the neurotransmitter acetylcholine (ACh). Just as muscarinic receptors are named such because they are also activated by muscarine, nicotinic receptors can be opened not only by acetylcholine but also by nicotine —hence the name "nicotinic". www.MedChemExpress.com 1 nAChR Inhibitors & Modulators (+)-Sparteine (-)-(S)-B-973B Cat. No.: HY-W008350 Cat. No.: HY-114269 Bioactivity: (+)-Sparteine is a natural alkaloid acting as a ganglionic Bioactivity: (-)-(S)-B-973B is a potent allosteric agonist and positive blocking agent. (+)-Sparteine competitively blocks nicotinic allosteric modulator of α7 nAChR, with antinociceptive ACh receptor in the neurons. activity [1]. Purity: 98.0% Purity: 99.93% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 10mM x 1mL in Water, Size: 10mM x 1mL in DMSO, 100 mg 5 mg, 10 mg, 50 mg, 100 mg (±)-Epibatidine A-867744 (CMI 545) Cat. No.: HY-101078 Cat. No.: HY-12149 Bioactivity: (±)-Epibatidine is a nicotinic agonist. (±)-Epibatidine is a Bioactivity: A-867744 is a positive allosteric modulator of α7 nAChRs (IC50 neuronal nAChR agonist. values are 0.98 and 1.12 μM for human and rat α7 receptor ACh-evoked currents respectively, in X.
    [Show full text]
  • Pharmacokinetic Limitations on Effects of an Alpha7-Nicotinic Receptor Agonist in Schizophrenia: Randomized Trial with an Extended-Release Formulation
    Neuropsychopharmacology (2018) 43, 583–589 © 2018 American College of Neuropsychopharmacology. All rights reserved 0893-133X/18 www.neuropsychopharmacology.org Pharmacokinetic Limitations on Effects of an Alpha7-Nicotinic Receptor Agonist in Schizophrenia: Randomized Trial with an Extended-Release Formulation 1 2 2 2 3 4 William R Kem , Ann Olincy , Lynn Johnson , Josette Harris , Brandie D Wagner , Robert W Buchanan , 5 ,2 Uwe Christians and Robert Freedman* 1 2 Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, FL, USA; Department of Psychiatry F-546, 3 University of Colorado School of Medicine, Aurora, CO, USA; Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, 4 CO, USA; Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA; 5 Department of Anesthesiology, University of Colorado School of Medicine, Aurora, CO, USA The aim of the trial was to assess whether extending plasma levels of the alpha7-nicotinic acetylcholine receptor (nAChR) agonist 3-(2,4- dimethoxybenzylidene)-anabaseine (DMXB-A) over time enhances its cognitive effects in schizophrenia. Both smoking and non-smoking patients were studied, to determine whether effects differ between these two groups. Forty-three smokers and thirty-seven non-smokers who met DSM-IV criteria for schizophrenia were enrolled in a double-blind, randomized, placebo-controlled 1 month trial. DMXB-A 150 mg was formulated with hypromellose to produce extended release over 4 h and administered four times daily. The primary outcome (the Neurocognitive Composite of the MATRICS Consensus Cognitive Battery) and secondary outcomes (the MATRICS Attention-Vigilance Domain and P50 gating), showed no significant effect.
    [Show full text]
  • Ligand-Gated Ion Channels
    S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2015/16: Ligand-gated ion channels. British Journal of Pharmacology (2015) 172, 5870–5903 THE CONCISE GUIDE TO PHARMACOLOGY 2015/16: Ligand-gated ion channels Stephen PH Alexander1, John A Peters2, Eamonn Kelly3, Neil Marrion3, Helen E Benson4, Elena Faccenda4, Adam J Pawson4, Joanna L Sharman4, Christopher Southan4, Jamie A Davies4 and CGTP Collaborators L 1 School of Biomedical Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK, N 2Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK, 3School of Physiology and Pharmacology, University of Bristol, Bristol, BS8 1TD, UK, 4Centre for Integrative Physiology, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/ doi/10.1111/bph.13350/full. Ligand-gated ion channels are one of the eight major pharmacological targets into which the Guide is divided, with the others being: ligand-gated ion channels, voltage- gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets.
    [Show full text]
  • Activities of Nicotinic Acetylcholine Receptors Modulate Neurotransmission and Synaptic Architecture
    NEURAL REGENERATION RESEARCH December 2014,Volume 9,Issue 24 www.nrronline.org INVITED REVIEW Activities of nicotinic acetylcholine receptors modulate neurotransmission and synaptic architecture Akira Oda1, Hidekazu Tanaka2 1 CNS Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 2-26-1, Muraoka-higashi, Fujisawa, Kanagawa 251-8555, Japan 2 Laboratory of Pharmacology, Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, 1-1-1, Noji-higashi, Kusatsu, Shiga 525-8577, Japan Abstract Corresponding author: The cholinergic system is involved in a broad spectrum of brain function, and its failure has Hidekazu Tanaka, M.D., Ph.D., been implicated in Alzheimer’s disease. Acetylcholine transduces signals through muscarinic Laboratory of Pharmacology, Department and nicotinic acetylcholine receptors, both of which influence synaptic plasticity and cognition. of Biomedical Sciences, College of Life However, the mechanisms that relate the rapid gating of nicotinic acetylcholine receptors to per- Sciences, Ritsumeikan University, sistent changes in brain function have remained elusive. Recent evidence indicates that nicotinic [email protected]. acetylcholine receptors activities affect synaptic morphology and density, which result in per- sistent rearrangements of neural connectivity. Further investigations of the relationships between doi:10.4103/1673-5374.147943 nicotinic acetylcholine receptors and rearrangements of neural circuitry in the central nervous http://www.nrronline.org/ system may help understand the pathogenesis of Alzheimer’s disease. Accepted: 2014-11-03 Key Words: cholinergic system; nicotinic acetylcholine receptors (nAChRs); Alzheimer’s disease (AD); synaptic transmission; synaptic plasticity; synaptic morphology; dendritic spine remodeling; cognition Funding: Tanaka H is supported by the Takeda Science Foundation and JSPS KAKENHI Grant Number 19590247.
    [Show full text]
  • Drug Development in Alzheimer's Disease: the Contribution of PET and SPECT
    fphar-07-00088 March 29, 2016 Time: 15:21 # 1 View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Frontiers - Publisher Connector REVIEW published: 31 March 2016 doi: 10.3389/fphar.2016.00088 Drug Development in Alzheimer’s Disease: The Contribution of PET and SPECT Lieven D. Declercq1, Rik Vandenberghe2, Koen Van Laere3, Alfons Verbruggen1 and Guy Bormans1* 1 Laboratory for Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium, 2 Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium, 3 Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium Clinical trials aiming to develop disease-altering drugs for Alzheimer’s disease (AD), a neurodegenerative disorder with devastating consequences, are failing at an alarming rate. Poorly defined inclusion-and outcome criteria, due to a limited amount of objective biomarkers, is one of the major concerns. Non-invasive molecular imaging techniques, positron emission tomography and single photon emission (computed) tomography (PET and SPE(C)T), allow visualization and quantification of a wide variety of (patho)physiological processes and allow early (differential) diagnosis in many disorders. Edited by: Albert D. Windhorst, PET and SPECT have the ability to provide biomarkers that permit spatial assessment VU University Medical Center, of pathophysiological molecular changes and therefore objectively evaluate and follow Netherlands up therapeutic response, especially in the brain. A number of specific PET/SPECT Reviewed by: biomarkers used in support of emerging clinical therapies in AD are discussed in this Bashir M. Rezk, Southern University at New Orleans, review.
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]