cholinesterase inhibitors


Summary: Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system.

Top Publications

  1. ncbi Acetylcholinesterase--new roles for an old actor
    H Soreq
    Nat Rev Neurosci 2:294-302. 2001
  2. ncbi Cholinesterase inhibitors used in the treatment of Alzheimer's disease: the relationship between pharmacological effects and clinical efficacy
    David G Wilkinson
    Memory Assessment and Research Centre, Moorgreen Hospital, Southampton, UK
    Drugs Aging 21:453-78. 2004
  3. ncbi Cholinesterase inhibitors and memory
    Giancarlo Pepeu
    Department of Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy
    Chem Biol Interact 187:403-8. 2010
  4. ncbi Cholinesterase inhibitors: new roles and therapeutic alternatives
    Ezio Giacobini
    Department of Geriatrics, University of Geneva Medical School, University Hospitals of Geneva, CH 1226 Thonex Geneva, Switzerland
    Pharmacol Res 50:433-40. 2004
  5. ncbi Alzheimer's disease
    Kaj Blennow
    Clinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, Sahlgren s University Hospital, Molndal, Sweden
    Lancet 368:387-403. 2006
  6. pmc The cholinergic hypothesis of Alzheimer's disease: a review of progress
    P T Francis
    Dementia Research Laboratory, Neuroscience Research Centre, Guy s, King s and St Thomas Schools of Biomedical Sciences, King s College, London, UK
    J Neurol Neurosurg Psychiatry 66:137-47. 1999
  7. ncbi Donepezil and memantine for moderate-to-severe Alzheimer's disease
    Robert Howard
    Institute of Psychiatry, King s College London, London SE5 8AF, United Kingdom
    N Engl J Med 366:893-903. 2012
  8. pmc Selective and irreversible inhibitors of mosquito acetylcholinesterases for controlling malaria and other mosquito-borne diseases
    Yuan Ping Pang
    Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, United States of America
    PLoS ONE 4:e6851. 2009
  9. ncbi Brain acetylcholinesterase activity controls systemic cytokine levels through the cholinergic anti-inflammatory pathway
    Valentin A Pavlov
    Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA
    Brain Behav Immun 23:41-5. 2009
  10. ncbi Acetylcholinesterase inhibitors: a patent review (2008 - present)
    Miroslav Pohanka
    University of Defense, Faculty of Military Health Sciences, Trebesska 1575, 50001 Hradec Kralove, Czech Republic
    Expert Opin Ther Pat 22:871-86. 2012

Detail Information

Publications340 found, 100 shown here

  1. ncbi Acetylcholinesterase--new roles for an old actor
    H Soreq
    Nat Rev Neurosci 2:294-302. 2001
    ..Although our understanding of the additional roles of acetylcholinesterase is incomplete, the time is ripe to summarize the evidence on a remarkable diversity of acetylcholinesterase functions...
  2. ncbi Cholinesterase inhibitors used in the treatment of Alzheimer's disease: the relationship between pharmacological effects and clinical efficacy
    David G Wilkinson
    Memory Assessment and Research Centre, Moorgreen Hospital, Southampton, UK
    Drugs Aging 21:453-78. 2004
    The deficiency in cholinergic neurotransmission in Alzheimer's disease has led to the development of cholinesterase inhibitors as the first-line treatment for symptoms of this disease...
  3. ncbi Cholinesterase inhibitors and memory
    Giancarlo Pepeu
    Department of Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy
    Chem Biol Interact 187:403-8. 2010
    A consensus exists that cholinesterase inhibitors (ChEIs) are efficacious for mild to moderate Alzheimer's Disease (AD). Unfortunately, the number of non-responders is large and the therapeutic effect is usually short-lasting...
  4. ncbi Cholinesterase inhibitors: new roles and therapeutic alternatives
    Ezio Giacobini
    Department of Geriatrics, University of Geneva Medical School, University Hospitals of Geneva, CH 1226 Thonex Geneva, Switzerland
    Pharmacol Res 50:433-40. 2004
    ..Clinical results demonstrate examples of versatility of cholinergic enhancement...
  5. ncbi Alzheimer's disease
    Kaj Blennow
    Clinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, Sahlgren s University Hospital, Molndal, Sweden
    Lancet 368:387-403. 2006
    ..This seminar reviews the key aspects of the disease, including epidemiology, genetics, pathogenesis, diagnosis, and treatment, as well as recent developments and controversies...
  6. pmc The cholinergic hypothesis of Alzheimer's disease: a review of progress
    P T Francis
    Dementia Research Laboratory, Neuroscience Research Centre, Guy s, King s and St Thomas Schools of Biomedical Sciences, King s College, London, UK
    J Neurol Neurosurg Psychiatry 66:137-47. 1999
    ..Indeed, three compounds have received European approval for the treatment of the cognitive symptoms of Alzheimer's disease, first tacrine and more recently, donepezil and rivastigmine, all of which are cholinesterase inhibitors.
  7. ncbi Donepezil and memantine for moderate-to-severe Alzheimer's disease
    Robert Howard
    Institute of Psychiatry, King s College London, London SE5 8AF, United Kingdom
    N Engl J Med 366:893-903. 2012
    Clinical trials have shown the benefits of cholinesterase inhibitors for the treatment of mild-to-moderate Alzheimer's disease. It is not known whether treatment benefits continue after the progression to moderate-to-severe disease.
  8. pmc Selective and irreversible inhibitors of mosquito acetylcholinesterases for controlling malaria and other mosquito-borne diseases
    Yuan Ping Pang
    Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, United States of America
    PLoS ONE 4:e6851. 2009
    ..These results support our view that the mosquito-specific Cys is a viable target for developing new mosquitocides to control disease vectors and to alleviate resistance problems with reduced toxicity toward non-target species...
  9. ncbi Brain acetylcholinesterase activity controls systemic cytokine levels through the cholinergic anti-inflammatory pathway
    Valentin A Pavlov
    Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA
    Brain Behav Immun 23:41-5. 2009
    ..Our data also indicate that a clinically used centrally-acting acetylcholinesterase inhibitor can be utilized to suppress abnormal inflammation to therapeutic advantage...
  10. ncbi Acetylcholinesterase inhibitors: a patent review (2008 - present)
    Miroslav Pohanka
    University of Defense, Faculty of Military Health Sciences, Trebesska 1575, 50001 Hradec Kralove, Czech Republic
    Expert Opin Ther Pat 22:871-86. 2012
    ..Beside toxins, drugs for treatment of Alzheimer's disease and myasthenia gravis, such as galantamine, donepezil, rivastigmine, tacrine, huperzine, pyridostigmine and neostigmine, are known...
  11. pmc Recombinant expression and biochemical characterization of the catalytic domain of acetylcholinesterase-1 from the African malaria mosquito, Anopheles gambiae
    Haobo Jiang
    Department of Entomology and Plant Pathology, Oklahoma State University, Stillwater, OK 74078, USA
    Insect Biochem Mol Biol 39:646-53. 2009
    ..Furthermore, we found that choline inhibited r-AgAChE1, a phenomenon related to the enzyme activity decrease at high concentrations of acetylcholine...
  12. ncbi Efficacy of an evidence-based cognitive stimulation therapy programme for people with dementia: randomised controlled trial
    Aimee Spector
    Department of Psychiatry and Behavioural Sciences, University College London, UK
    Br J Psychiatry 183:248-54. 2003
    ..A recent Cochrane review of reality orientation therapy identified the need for large, well-designed, multi-centre trials...
  13. ncbi A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD
    B Winblad
    Karolinska Institutet, Alzheimer s Disease Research Center, Division of Geriatric Medicine, Huddinge Hospital B, Stockholm, Sweden
    Neurology 57:489-95. 2001
    ..To evaluate the long-term clinical efficacy and safety of donepezil versus placebo over 1 year in patients with mild to moderate AD...
  14. ncbi Donepezil, an acetylcholinesterase inhibitor against Alzheimer's dementia, promotes angiogenesis in an ischemic hindlimb model
    Yoshihiko Kakinuma
    Department of Cardiovascular Control, Kochi Medical School, Nankoku, Kochi 783 8505, Japan
    J Mol Cell Cardiol 48:680-93. 2010
    ..The present study concludes that donepezil can act as a therapeutic tool to accelerate angiogenesis in cardiovascular disease patients...
  15. ncbi Are cholinesterase inhibitors effective in the management of the behavioral and psychological symptoms of dementia in Alzheimer's disease? A systematic review of randomized, placebo-controlled trials of donepezil, rivastigmine and galantamine
    Joanne Rodda
    Department of Mental Health Sciences, University College London, UK
    Int Psychogeriatr 21:813-24. 2009
  16. ncbi Beyond the cholinergic hypothesis: do current drugs work in Alzheimer's disease?
    Alessandro Martorana
    Clinica Neurologica, Dipartimento di Neuroscienze, Universita di Roma Tor Vergata, Rome, Italy
    CNS Neurosci Ther 16:235-45. 2010
  17. ncbi The serum protein and lipid oxidation marker levels in Alzheimer's disease and effects of cholinesterase inhibitors and antipsychotic drugs therapy
    F Sinem
    Department of Biochemistry, Istanbul University, Istanbul, Turkey
    Curr Alzheimer Res 7:463-9. 2010
    ..However, it is required further studies for the determination of clinical importance of these markers...
  18. ncbi Cholinesterase inhibitors and incidence of bradycardia in patients with dementia in the veterans affairs new England healthcare system
    Rohini K Hernandez
    Cooperative Studies Program, Massachusetts Veterans Epidemiology Research and Information Center, Veterans Affairs Boston Healthcare System, Boston, Massachusetts, USA
    J Am Geriatr Soc 57:1997-2003. 2009
    To quantify the association between cholinesterase inhibitors (ChE-Is) and a new diagnosis of bradycardia and to evaluate the clinical significance of bradycardia.
  19. ncbi Protective effect of rivastigmine against 3-nitropropionic acid-induced Huntington's disease like symptoms: possible behavioural, biochemical and cellular alterations
    Puneet Kumar
    Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India
    Eur J Pharmacol 615:91-101. 2009
    ..The results show that rivastigmine could be used as an effective therapeutic agent in the management of Huntington's disease and related conditions...
  20. ncbi Mortality risk in patients with dementia treated with antipsychotics versus other psychiatric medications
    Helen C Kales
    Serious Mental Illness Treatment Research and Evaluation Center, Health Services Research and Development, VA Ann Arbor Healthcare System, Ann Arbor, Ann Arbor, MI 48109, USA
    Am J Psychiatry 164:1568-76; quiz 1623. 2007
    ..Mortality rates in the year following new antipsychotic medication starts for neuropsychiatric symptoms of dementia were compared with rates after starts of other psychiatric medications...
  21. ncbi Acetylcholinesterase: 'classical' and 'non-classical' functions and pharmacology
    Israel Silman
    Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel
    Curr Opin Pharmacol 5:293-302. 2005
    ..Both of these actions involve the so-called 'peripheral' anionic site at the entrance to the active-site gorge. Novel anticholinesterases are targeted against this site, rather than against the active site at the bottom of the gorge...
  22. ncbi Can CSF biomarkers or pre-treatment progression rate predict response to cholinesterase inhibitor treatment in Alzheimer's disease?
    A K Wallin
    Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmo, Sweden
    Int J Geriatr Psychiatry 24:638-47. 2009
    ..A secondary objective was to evaluate whether treatment with ChEI changed progression...
  23. ncbi Alzheimer disease pharmacologic treatment and treatment research
    Lon S Schneider
    Keck School of Medicine, University of Southern California, 1540 Alcazar St, CHP 216, Los Angeles, CA 90033, USA
    Continuum (Minneap Minn) 19:339-57. 2013
    ..Current experimental drug development, including challenges to developing successful drugs for Alzheimer disease, are also reviewed and assessed...
  24. ncbi Targeting acetylcholinesterase to treat neurodegeneration
    Ulrike Holzgrabe
    Institute of Pharmacy and Food Chemistry, University of Wurzburg, Am Hubland, 97074 Wurzburg, Germany
    Expert Opin Ther Targets 11:161-79. 2007
    ..This dual action might be more beneficial for treatment of Alzheimer s disease than simple inhibition of the acetylcholine hydrolysis. Thus, the new bivalent ligands are the focus of this review...
  25. ncbi Economic evaluation of the impact of memantine on time to nursing home admission in the treatment of Alzheimer disease
    Jean Lachaine
    University of Montreal, Quebec
    Can J Psychiatry 56:596-604. 2011
    ..Our study aimed to evaluate the economic impact of the concomitant use of memantine and a ChEI, compared with a ChEI alone, in a Canadian population of patients with AD...
  26. ncbi Enhanced cholinergic transmission promotes recall in honeybees
    D Guez
    Faculty of Applied Science, University of Canberra, ACT, Australia
    J Insect Physiol 56:1341-8. 2010
    ..The results are also discussed in terms of their ecotoxicological consequences...
  27. ncbi Effect of donepezil and lercanidipine on memory impairment induced by intracerebroventricular streptozotocin in rats
    Swapnil Sonkusare
    Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, S A S Nagar 160062, Punjab, India
    Life Sci 77:1-14. 2005
    ..However, no reports are available regarding the cholinesterase inhibitors in this model...
  28. ncbi Caregiver preference for rivastigmine patches versus capsules for the treatment of Alzheimer disease
    Rafael Blesa
    Hospital de la Sta Creu i Sant Pau, Barcelona, Spain
    Neurology 69:S23-8. 2007
    ..Preference for the patch may indicate reduced caregiver stress, substantiated by greater satisfaction and less interference with daily life. These benefits may lead to improved compliance...
  29. ncbi Reality orientation therapy combined with cholinesterase inhibitors in Alzheimer's disease: randomised controlled trial
    Graziano Onder
    Department of Gerontology, Geriatrics and Psychiatry, Catholic University, Rome
    Br J Psychiatry 187:450-5. 2005
    Reality orientation therapy combined with cholinesterase inhibitors has not been evaluated in patients with Alzheimer's disease.
  30. ncbi An overview of phenserine tartrate, a novel acetylcholinesterase inhibitor for the treatment of Alzheimer's disease
    Nigel H Greig
    Drug Design and Development Section, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
    Curr Alzheimer Res 2:281-90. 2005
    ..Further randomized, double-blind, placebo-controlled Phase III studies assessing the efficacy, safety/tolerability and potential disease-modifying effects of (-)-phenserine in patients with AD are currently ongoing...
  31. ncbi Effects of donepezil on verbal memory after semantic processing in healthy older adults
    David B Fitzgerald
    Department of Neurology, University of Florida, Jacksonville, FL 32610 0236, USA
    Cogn Behav Neurol 21:57-64. 2008
    ..To learn if acetylcholinesterase inhibitors alter verbal recall by improving semantic encoding in a double-blind randomized placebo-controlled trial...
  32. pmc Donepezil improves episodic memory in young individuals vulnerable to the effects of sleep deprivation
    Lisa Y M Chuah
    Cognitive Neuroscience Laboratory, Duke NUS Graduate Medical School, Singapore
    Sleep 32:999-1010. 2009
    ..We investigated if donepezil, a long-acting orally administered cholinesterase inhibitor, would reduce episodic memory deficits associated with 24 h of sleep deprivation...
  33. pmc Butyrylcholinesterase for protection from organophosphorus poisons: catalytic complexities and hysteretic behavior
    Patrick Masson
    Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198 5950, USA
    Arch Biochem Biophys 494:107-20. 2010
    ..It is proposed, but not yet proven, that low dose exposure involves OP modification of proteins that have no active site serine...
  34. ncbi Pyrano[3,2-c]quinoline-6-chlorotacrine hybrids as a novel family of acetylcholinesterase- and beta-amyloid-directed anti-Alzheimer compounds
    Pelayo Camps
    Facultat de Farmacia, Universitat de Barcelona, Barcelona, Spain
    J Med Chem 52:5365-79. 2009
  35. pmc Structural insights into substrate traffic and inhibition in acetylcholinesterase
    Jacques Philippe Colletier
    Laboratoire de Biophysique Moleculaire, Institut de Biologie Structurale CEA CNRS UJF, Grenoble Cedex, France
    EMBO J 25:2746-56. 2006
    ..At the higher concentration, substrate inhibition arises from prevention of exit of acetate due to binding of two substrate molecules within the active-site gorge...
  36. ncbi Change in perfusion, hallucinations and fluctuations in consciousness in dementia with Lewy bodies
    John T O'Brien
    Institute for Ageing and Health, University of Newcastle upon Tyne, Wolfson Research Centre, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne, NE4 6BE, UK
    Psychiatry Res 139:79-88. 2005
    ..We have identified important neural correlates of key clinical features in Lewy body dementia and postulate that the associations can be understood through the influence of the cholinergic system on attention...
  37. ncbi Microvasculature changes and cerebral amyloid angiopathy in Alzheimer's disease and their potential impact on therapy
    Roy O Weller
    Clinical Neurosciences, University of Southampton School of Medicine, LD74, South Laboratory and Pathology Block, Southampton General Hospital, Southampton SO166YD, UK
    Acta Neuropathol 118:87-102. 2009
    ..Changes in the cerebral microvasculature with age have a potential impact on therapy with cholinesterase inhibitors and especially on immunotherapy that removes Abeta from plaques in the brain, but results in an increase ..
  38. ncbi Antibacterial, anti-inflammatory, anti-cholinesterase and mutagenic effects of extracts obtained from some trees used in South African traditional medicine
    I M S Eldeen
    Research Centre for Plant Growth and Development, School of Biological and Conservation Sciences, University of KwaZulu Natal Pietermaritzburg, Scottsville, South Africa
    J Ethnopharmacol 102:457-64. 2005
    ..The lowest IC(50) value was 0.04 mg ml(-1) obtained with an ethanol bark extract of Combretum kraussii. None of the investigated plants showed any potential mutagenic effects...
  39. pmc Effectiveness and tolerability of high-dose (23 mg/d) versus standard-dose (10 mg/d) donepezil in moderate to severe Alzheimer's disease: A 24-week, randomized, double-blind study
    Martin R Farlow
    Department of Neurology, Indiana University School of Medicine, Indianapolis, 46202, USA
    Clin Ther 32:1234-51. 2010
    ..We hypothesized that the loss of initial therapeutic benefit over time may be mitigated by higher doses of a cholinesterase inhibitor...
  40. ncbi Mechanisms of neuroprotective effects of nicotine and acetylcholinesterase inhibitors: role of alpha4 and alpha7 receptors in neuroprotection
    Akinori Akaike
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo ku, Kyoto 606 8501, Japan
    J Mol Neurosci 40:211-6. 2010
    ..These results suggest that nicotine as well as AChE inhibitors, donepezil and galantamine, prevent glutamate neurotoxicity through alpha4 and alpha7 nAChRs and the PI3K-Akt pathway...
  41. ncbi Changes in neuronal acetylcholinesterase gene expression and division of labor in honey bee colonies
    M Shapira
    Department of Biological Chemistry, The Life Sciences Institute, The Hebrew University of Jerusalem, Givat Ram
    J Mol Neurosci 17:1-12. 2001
  42. ncbi Acetylcholinesterase inhibitors from plants
    Pulok K Mukherjee
    Department of Pharmacy, Pharmacognosy Research Laboratories, Franklin Wilkins Building, King s College London, 150 Stamford Street, London SE1 9NH, UK
    Phytomedicine 14:289-300. 2007
    ..Numerous phytoconstituents and promising plant species as AChE inhibitors are being reported in this communication...
  43. ncbi Indole alkaloids from Tabernaemontana australis (Muell. Arg) Miers that inhibit acetylcholinesterase enzyme
    Marcelo T Andrade
    Instituto de Quimica, Universidade Federal do Rio de Janeiro, Centro de Tecnologia, Bloco A, Cidade Universitaria, 21945 970 Rio de Janeiro, RJ, Brazil
    Bioorg Med Chem 13:4092-5. 2005
    ..01mM) by TLC assay using the modified Ellman's method...
  44. pmc Selective and irreversible inhibitors of aphid acetylcholinesterases: steps toward human-safe insecticides
    Yuan Ping Pang
    Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, United States of America
    PLoS ONE 4:e4349. 2009
  45. ncbi Acetylcholinesterase inhibitors and memantine for neuroenhancement in healthy individuals: a systematic review
    Dimitris Repantis
    Department of Psychiatry, Charite Universitatsmedizin Berlin, Campus Benjamin Franklin, Eschenallee 3, 14050 Berlin, Germany
    Pharmacol Res 61:473-81. 2010
    ..At the moment, the research that would support or oppose the use of acetylcholinesterase inhibitors and memantine for neuroenhancement by healthy individuals has not yet been performed...
  46. ncbi Long-term outcome and prediction models of activities of daily living in Alzheimer disease with cholinesterase inhibitor treatment
    Carina Wattmo
    Department of Clinical Sciences, Clinical Memory Research Unit, Malmo, Lund University, Sweden
    Alzheimer Dis Assoc Disord 25:63-72. 2011
    ..AD severity at baseline is a key factor in obtaining reliable clinical prognoses of the long-term ADL ability. The dosage of ChEI treatment could possibly lead to a different functional outcome...
  47. ncbi Disease progression meta-analysis model in Alzheimer's disease
    Kaori Ito
    Pfizer Global Research and Development, New London, CT, USA
    Alzheimers Dement 6:39-53. 2010
    ..The model was used to estimate disease progression for both placebo-treated patients and acetylcholinesterase (AChE)-inhibitor treated patients, and factors that affected disease progression...
  48. ncbi Management of behavioral problems in Alzheimer's disease
    Serge Gauthier
    Alzheimer s Disease and Related Disorders Unit, McGill Center for Studies in Aging, Douglas Mental Health University Institute, Montreal, Canada
    Int Psychogeriatr 22:346-72. 2010
    ..Pharmacological treatment options, such as antipsychotics, antidepressants, anticonvulsants, cholinesterase inhibitors and memantine, need careful consideration of the benefits and limitations of each drug class.
  49. pmc Cholinesterase inhibitors in mild cognitive impairment: a systematic review of randomised trials
    Roberto Raschetti
    National Center for Epidemiology, Surveillance and Health Promotion, National Institute of Health, Rome, Italy
    PLoS Med 4:e338. 2007
    ..of MCI as a clinical entity, clinical trials have been conducted in the attempt to study the role of cholinesterase inhibitors (ChEIs) currently approved for symptomatic treatment of mild to moderate Alzheimer disease (AD), in ..
  50. ncbi Cholinergic augmentation modulates visual task performance in sleep-deprived young adults
    Lisa Y M Chuah
    Cognitive Neuroscience Laboratory, Duke National University of Singapore Graduate Medical School, Singapore
    J Neurosci 28:11369-77. 2008
    ..Cholinergic augmentation can alleviate these deficits in individuals vulnerable to the effects of sleep deprivation, but it may have neutral or negative effects on those resistant to sleep deprivation...
  51. doi Multi-target-directed ligands to combat neurodegenerative diseases
    Andrea Cavalli
    Department of Pharmaceutical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
    J Med Chem 51:347-72. 2008
  52. ncbi The experimental Alzheimer's disease drug posiphen [(+)-phenserine] lowers amyloid-beta peptide levels in cell culture and mice
    Debomoy K Lahiri
    Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, 791 Union Drive, Indianapolis, IN 46202, USA
    J Pharmacol Exp Ther 320:386-96. 2007
    ..Posiphen, like phenserine, can lower Abeta via multiple mechanisms and represents an interesting drug candidate for AD treatment...
  53. ncbi Vitamin E and donepezil for the treatment of mild cognitive impairment
    Ronald C Petersen
    Mayo Clinic College of Medicine, Rochester, Minn, USA
    N Engl J Med 352:2379-88. 2005
    ..Mild cognitive impairment is a transitional state between the cognitive changes of normal aging and early Alzheimer's disease...
  54. pmc Long-term effects of the concomitant use of memantine with cholinesterase inhibition in Alzheimer disease
    O L Lopez
    Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    J Neurol Neurosurg Psychiatry 80:600-7. 2009
    Patients using cholinesterase inhibitors (ChEIs) have a delay in nursing home (NH) admission compared with those who were not using the medication...
  55. ncbi Intranasal delivery: physicochemical and therapeutic aspects
    Henry R Costantino
    Nastech Pharmaceutical Company, Inc, Bothell, WA 98021, USA
    Int J Pharm 337:1-24. 2007
    ..Case examples are provided to illustrate the utility of IN dosing. It is anticipated that the present review will prove useful for formulation scientists considering IN delivery as a delivery route...
  56. ncbi Effects of donepezil, galantamine and rivastigmine in 938 Italian patients with Alzheimer's disease: a prospective, observational study
    Aurelia Santoro
    Department of Experimental Pathology, University of Bologna, Via S Giacomo 12, Bologna, Italy
    CNS Drugs 24:163-76. 2010
    ..g. health status and co-morbidities) associated with a complex disease such as AD in elderly people...
  57. ncbi Serotonin inhibition of synaptic transmission: Galpha(0) decreases the abundance of UNC-13 at release sites
    S Nurrish
    Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA
    Neuron 24:231-42. 1999
  58. ncbi Cholinesterase inhibitors: A new class of psychotropic compounds
    J L Cummings
    Department of Neurology, UCLA School of Medicine, Los Angeles, CA 90095 1769, USA
    Am J Psychiatry 157:4-15. 2000
    ..This article reviews evidence indicating that acetylcholinesterase inhibitors have psychotropic properties...
  59. ncbi Cholinergic protection via alpha7 nicotinic acetylcholine receptors and PI3K-Akt pathway in LPS-induced neuroinflammation
    Ethika Tyagi
    Division of Pharmacology, Central Drug Research Institute, Lucknow, Uttar Pradesh, India
    Neurochem Int 56:135-42. 2010
  60. ncbi Two fast screening methods (GC-MS and TLC-ChEI assay) for rapid evaluation of potential anticholinesterasic indole alkaloids in complex mixtures
    Ivo J C Vieira
    Centro de Ciência e Tecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Av Alberto Lamego 2000, Campos dos Goytacazes, RJ, Brazil
    An Acad Bras Cienc 80:419-26. 2008
    ..In this work two fast screening techniques were combined in order to easily identify novel cholinesterase inhibitors (ChEI)...
  61. pmc Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer's disease: a systematic review and meta-analysis
    Richard A Hansen
    School of Pharmacy, Division of Pharmaceutical Outcomes and Policy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Clin Interv Aging 3:211-25. 2008
    Pharmacologic treatments for Alzheimer's disease include the cholinesterase inhibitors donepezil, galantamine, and rivastigmine...
  62. ncbi Anticholinesterase activity of 7-methoxyflavones isolated from Kaempferia parviflora
    Pattara Sawasdee
    Natural Products Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
    Phytother Res 23:1792-4. 2009
    ..Interestingly, 5,7-dimethoxyflavone (7) exhibited strong selectivity for BChE over AChE which may be of great interest to modify as a treatment agent for Alzheimer's disease...
  63. ncbi The use of cholinesterase inhibitors and the risk of myocardial infarction and death: a nationwide cohort study in subjects with Alzheimer's disease
    Peter Nordström
    Department of Community Medicine and Rehabilitation, Geriatric Medicine, Umea University, Umeå 90185, Sweden
    Eur Heart J 34:2585-91. 2013
    b>Cholinesterase inhibitors (ChEIs) are used for symptomatic treatment of Alzheimer's disease. These drugs have vagotonic and anti-inflammatory properties that could be of interest also with respect to cardiovascular disease...
  64. pmc Occupational determinants of serum cholinesterase inhibition among organophosphate-exposed agricultural pesticide handlers in Washington State
    Jonathan N Hofmann
    Department of Epidemiology, University of Washington, Seattle, Washington, USA
    Occup Environ Med 67:375-86. 2010
    ..To identify potential risk factors for serum cholinesterase (BuChE) inhibition among agricultural pesticide handlers exposed to organophosphate (OP) and N-methyl-carbamate (CB) insecticides...
  65. ncbi Acetylcholinesterase inhibitors for Alzheimer's disease: anti-inflammatories in acetylcholine clothing!
    N Tabet
    Postgraduate Medical School, University of Brighton, Falmer, Brighton, BN1 9PH, UK
    Age Ageing 35:336-8. 2006
    ..Evidence points to a possible anti-inflammatory role for these agents as well...
  66. pmc Impact of geriatric comorbidity and polypharmacy on cholinesterase inhibitors prescribing in dementia
    Falk Hoffmann
    University of Bremen, Centre for Social Policy Research, Division Health Economics, Health Policy and Outcomes Research, Bremen, Germany
    BMC Psychiatry 11:190. 2011
    Although most guidelines recommend the use of cholinesterase inhibitors (ChEIs) for mild to moderate Alzheimer's Disease, only a small proportion of affected patients receive these drugs...
  67. ncbi A large, naturalistic, community-based study of rivastigmine in mild-to-moderate AD: the EXTEND Study
    Serge Gauthier
    McGill Centre for Studies in Aging, Douglas Hospital, Montreal, Quebec, Canada
    Curr Med Res Opin 22:2251-65. 2006
  68. ncbi Antioxidant activity, acetylcholinesterase inhibition, iridoid content and mutagenic evaluation of Leucosidea sericea
    Adeyemi O Aremu
    Research Centre for Plant Growth and Development, School of Biological and Conservation Sciences, University of KwaZulu Natal Pietermaritzburg, Private Bag X01, Scottsville 3209, South Africa
    Food Chem Toxicol 49:1122-8. 2011
    ..These findings suggest the safety as well as the potential of L. sericea as a possible source of novel/alternative antioxidant and acetylcholinesterase inhibitory compounds...
  69. ncbi A six-month double-blind, randomized, placebo-controlled study of a transdermal patch in Alzheimer's disease--rivastigmine patch versus capsule
    Bengt Winblad
    Karolinska Institutet Alzheimer Research Center, Stockholm, Sweden
    Int J Geriatr Psychiatry 22:456-67. 2007
    ..To compare the efficacy, safety and tolerability of a novel rivastigmine transdermal patch with conventional rivastigmine capsules and placebo in patients with Alzheimer's disease (AD)...
  70. ncbi Effect of rivastigmine on delay to diagnosis of Alzheimer's disease from mild cognitive impairment: the InDDEx study
    Howard H Feldman
    Division of Neurology, University of British Columbia Hospital, Vancouver, Canada
    Lancet Neurol 6:501-12. 2007
    ..To assess the effect of rivastigmine in patients with mild cognitive impairment (MCI) on the time to clinical diagnosis of Alzheimer's disease (AD) and the rate of cognitive decline...
  71. ncbi Enhanced pesticide sensitivity of novel housefly acetylcholinesterases: a new tool for the detection of residual pesticide contamination
    Furong Tan
    Biotechnology Research Institute, Shanghai Academy of Agriculture Sciences, 2901 Beidi Road, Shanghai 201106, China
    Bioprocess Biosyst Eng 34:305-14. 2011
    ..The AChE enzyme obtained by this method could be used to detect the organophosphate and carbamate insecticide residues in fruits and vegetables, a characteristic of great potential research and industrial application...
  72. pmc Influence of apolipoprotein E varepsilon4 on rates of cognitive and functional decline in mild cognitive impairment
    Danielle C Whitehair
    Department of Neurosciences, University of California, San Diego, CA, USA
    Alzheimers Dement 6:412-9. 2010
    ..We examine the prospective association of APOE varepsilon4 allele status on measures of cognitive and functional decline in subjects with amnestic MCI (aMCI)...
  73. pmc Galantamine-induced amyloid-{beta} clearance mediated via stimulation of microglial nicotinic acetylcholine receptors
    Kazuyuki Takata
    Department of Neurobiology, Kyoto Pharmaceutical University, Misasagi, Yamashina ku, Kyoto 607 8414, Japan
    J Biol Chem 285:40180-91. 2010
    ..In conclusion, we propose a further advantage of galantamine in clinical AD treatment and microglial nAChRs as a new therapeutic target...
  74. ncbi Synthesis, biological evaluation, and molecular modeling of donepezil and N-[(5-(benzyloxy)-1-methyl-1H-indol-2-yl)methyl]-N-methylprop-2-yn-1-amine hybrids as new multipotent cholinesterase/monoamine oxidase inhibitors for the treatment of Alzheimer's di
    Irene Bolea
    Departament de Bioquı́mica i Biologı́a Molecular, Facultat de Medicina, Institut de Neurociencies, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona, Spain
    J Med Chem 54:8251-70. 2011
    ..Overall, the results suggest that the new compounds are promising multitarget drug candidates with potential impact for Alzheimer's disease therapy...
  75. ncbi Pharmacotherapies for Alzheimer's disease: beyond cholinesterase inhibitors
    Haythum O Tayeb
    Department of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, MA 02478, USA
    Pharmacol Ther 134:8-25. 2012
    ..In this review, different pharmacological drugs and therapeutic approaches will be discussed, with an emphasis on novel therapies that are currently being investigated in clinical trials...
  76. ncbi The effect of donepezil on sleep and REM sleep EEG in patients with Alzheimer disease: a double-blind placebo-controlled study
    Walterandré dos Santos Moraes
    Psychobiology Department, Universidade Federal de Sao Paulo, Brazil
    Sleep 29:199-205. 2006
    ..Examine the effects of donepezil on sleep and rapid eye movement (REM) sleep electroencephalogram (EEG) in patients with Alzheimer disease, using polysomnography, and the correlation between REM sleep EEG parameters and cognitive scores...
  77. ncbi Assessment of Clarias batrachus as a source of acetylcholinesterase (AchE) for the detection of insecticides
    L G Tham
    Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, University Putra Malaysia, 43400 Serdang, Selangor, Malaysia
    J Environ Biol 30:135-8. 2009
    ..53-22.58) and 418.80 (390.60-451.60) microg l(-1), respectively. The results showed that C. batrachus have the potential to be used as a cheaper and more readily available source of AChE than other more commercially available sources...
  78. ncbi A review on cholinesterase inhibitors for Alzheimer's disease
    Preet Anand
    Department of Chemistry, Punjabi University, Patiala, 147002, India
    Arch Pharm Res 36:375-99. 2013
    ..b>Cholinesterase inhibitors enhance cholinergic transmission directly by inhibiting the enzyme acetylcholinesterase (AChE) which ..
  79. ncbi Exposure to nerve agents: from status epilepticus to neuroinflammation, brain damage, neurogenesis and epilepsy
    Marcio de Araujo Furtado
    Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
    Neurotoxicology 33:1476-90. 2012
    ..These studies are very necessary for current military and civilian treatment regimens, against OP nerve agent exposure, which fail to prevent SE resulting in severe neuropathology and epilepsy...
  80. pmc A role for solvents in the toxicity of agricultural organophosphorus pesticides
    Michael Eddleston
    Clinical Pharmacology Unit, University BHF Centre for Cardiovascular Science, University of Edinburgh, UK
    Toxicology 294:94-103. 2012
    ..Reformulation of OP insecticides to ensure that the agricultural product has lower mammalian toxicity could result in fewer deaths after suicidal ingestion and rapidly reduce global suicide rates...
  81. ncbi Cholinesterase inhibitors: a patent review (2007 - 2011)
    Cristobal de Los Rios
    Instituto de Investigacion Sanitaria, Servicio de Farmacologia Clinica, Hospital Universitario de la Princesa, C Diego de Leon, 62, 28006 Madrid, Spain
    Expert Opin Ther Pat 22:853-69. 2012
    b>Cholinesterase inhibitors participate in the maintenance of the levels of the neurotransmitter acetylcholine by inhibiting the enzymes implicated in its degradation, namely, butyrylcholinesterase and acetylcholinesterase...
  82. ncbi The effect of mixtures of organophosphate and carbamate pesticides on acetylcholinesterase and application of chemometrics to identify pesticides in mixtures
    K Mwila
    Department of Biochemistry, Microbiology and Biotechnology, Rhodes University, PO Box 94, Grahamstown, 6140, South Africa
    Environ Monit Assess 185:2315-27. 2013
    ..This is also the first study where an ANN was able to utilise data from the inhibition of a single enzyme to differentiate five different pesticides and their concentrations from mixtures...
  83. ncbi Functional analysis and molecular characterization of two acetylcholinesterases from the German cockroach, Blattella germanica
    Y H Kim
    Department of Agricultural Biotechnology, Seoul National University, Seoul, Korea
    Insect Mol Biol 19:765-76. 2010
    ..BgAChE2 appeared to have a collagen-GPI-fused tail. Based on the kinetic and molecular properties, tissue distribution and abundance, BgAChE1 was confirmed to play a major role in postsynaptic transmission...
  84. ncbi Discontinuation of donepezil for the treatment of Alzheimer's disease in geriatric practice
    Hiroyuki Umegaki
    Department of Geriatrics, Nagoya University Graduate School of Medicine, Aichi, Japan
    Int Psychogeriatr 20:800-6. 2008
    ..In the current study we surveyed the discontinuation of donepezil, a cholinesterase inhibitor, for the treatment of Alzheimer's disease in a Japanese geriatric outpatient clinic in a university hospital...
  85. pmc Cholinergic enhancement reduces spatial spread of visual responses in human early visual cortex
    Michael A Silver
    School of Optometry, University of California, Berkeley, Berkeley, CA 94720, USA
    Neuron 60:904-14. 2008
    ..These findings demonstrate that acetylcholine regulates spatial integration in human visual cortex...
  86. ncbi Screening of Korean herbal medicines used to improve cognitive function for anti-cholinesterase activity
    M H Oh
    Department of Pharmacy, Pharmacognosy Research Laboratories, King s College London, Franklin Wilkins Building, 150 Stamford Street, London SE1 8WA, UK
    Phytomedicine 11:544-8. 2004
    ..calamus and E. koreanum. The possible bases for the reputation of these and the other herbs tested are discussed in the light of previous investigations into their chemistry and biological activity...
  87. ncbi The in vitro screening for acetylcholinesterase inhibition and antioxidant activity of medicinal plants from Portugal
    A Ferreira
    Department of Chemistry and Biochemistry, University of Lisbon, Campo Grande, 1749 016 Lisboa, Portugal
    J Ethnopharmacol 108:31-7. 2006
    ..Hypericum undulatum, Melissa officinalis and Laurus nobilis showed both high AChE inhibitory capacity and antioxidant activity...
  88. ncbi Rivastigmine transdermal patch and capsule in Alzheimer's disease: influence of disease stage on response to therapy
    Martin R Farlow
    Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA
    Int J Geriatr Psychiatry 26:1236-43. 2011
    ..This exploratory, hypothesis-forming analysis assessed response to rivastigmine according to severity of dementia at baseline...
  89. ncbi Efficacy of cognitive rehabilitation in patients with mild cognitive impairment treated with cholinesterase inhibitors
    Luca Rozzini
    Department of Neurology, University of Brescia, Italy
    Int J Geriatr Psychiatry 22:356-60. 2007
    ..The high rate of conversion from MCI to AD makes early treatment an important clinical issue. Recent evidence suggests that cognitive training intervention may reduce the rate of progression to AD...
  90. ncbi Comparison of acute neurobehavioral and cholinesterase inhibitory effects of N-methylcarbamates in rat
    Katherine L McDaniel
    Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA
    Toxicol Sci 98:552-60. 2007
    ..Thus, motor activity decreases are highly predictive of ChE inhibition for N-methyl carbamates, and vice versa...
  91. ncbi Effect of the cholinesterase inhibitor donepezil on cardiac remodeling and autonomic balance in rats with heart failure
    Yoshihisa Okazaki
    Department of Artificial Organ Medicine, Division of Surgical Medicine, Osaka University Graduate School of Medicine, 2 2 Yamadaoka, Suita, Osaka 565 0871, Japan
    J Physiol Sci 60:67-74. 2010
    ..These findings indicated that donepezil reproduced the anti-remodeling effect of electrical vagal stimulation. Further studies are warranted to evaluate the clinical usefulness of donepezil in heart failure...
  92. ncbi A novel endophytic Huperzine A-producing fungus, Shiraia sp. Slf14, isolated from Huperzia serrata
    D Zhu
    Key Laboratory of Protection and Utilization of Subtropic Plant Resources of Jiangxi Province, Jiangxi Normal University, Nanchang, China
    J Appl Microbiol 109:1469-78. 2010
    ..To characterize and identify a novel Huperzine A (HupA)-producing fungal strain Slf14 isolated from Huperzia serrata (Thunb. ex Murray) Trev. in China...
  93. pmc Unwarranted administration of acetylcholinesterase inhibitors can impair genioglossus and diaphragm muscle function
    Matthias Eikermann
    Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02114 2696, USA
    Anesthesiology 107:621-9. 2007
    ..The authors hypothesized that cholinesterase inhibition when given the in absence of neuromuscular blockade (NB) would decrease upper airway dilatory muscle activity and consequently upper airway volume...
  94. ncbi Switching cholinesterase inhibitors in older adults with dementia
    Fadi Massoud
    Centre Hospitalier de l Universite de Montreal CHUM, Hopital Notre Dame, Service de Geriatrie, Montreal, Quebec, Canada
    Int Psychogeriatr 23:372-8. 2011
    b>Cholinesterase inhibitors (ChEIs) represent the mainstay of symptomatic treatment in Alzheimer's disease. Three medications belonging to this class are presently widely available...
  95. ncbi Predicting time to nursing home placement based on activities of daily living scores--a modelling analysis using data on Alzheimer's disease patients receiving rivastigmine or donepezil
    Hind T Hatoum
    Center for Pharmacoeconomic Research, the University of Illinois at Chicago UIC, Chicago, IL, USA
    J Med Econ 12:98-103. 2009
    ..To quantify the impact of activities of daily living (ADL) scores on the risk of nursing home placement (NHP) in Alzheimer's disease (AD) patients...
  96. ncbi Anti-inflammatory, anticholinesterase, antioxidant and phytochemical properties of medicinal plants used for pain-related ailments in South Africa
    O A Fawole
    Research Centre for Plant Growth and Development, School of Biological and Conservation Sciences, University of KwaZulu Natal Pietermaritzburg, Private Bag X01, Scottsville 3209, South Africa
    J Ethnopharmacol 127:235-41. 2010
    ..Extracts of seven South African medicinal plants used traditionally for the treatment of pain-related ailments were evaluated...
  97. ncbi A 25-week, open-label trial investigating rivastigmine transdermal patches with concomitant memantine in mild-to-moderate Alzheimer's disease: a post hoc analysis
    Martin R Farlow
    Department of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Curr Med Res Opin 26:263-9. 2010
    ..To investigate the tolerability and efficacy of the rivastigmine transdermal patch in patients with mild-to-moderate Alzheimer's disease receiving concomitant memantine...
  98. ncbi Reversal of neuromuscular block
    A Srivastava
    University of Liverpool Critical Care Research Unit, School of Clinical Science, Daulby Street, Liverpool, UK
    Br J Anaesth 103:115-29. 2009
    ..As yet, the extent of any side-effects that may occur with this new antagonist is not fully known, although rarely adverse cardiovascular effects (hypotension, hypertension, prolonged QT interval) have already been reported...
  99. ncbi Management of agitation and aggression associated with Alzheimer's disease: controversies and possible solutions
    Clive Ballard
    Wolfson Centre for Age Related Diseases, King s College London, London, UK
    Curr Opin Psychiatry 22:532-40. 2009
    ..The purpose of this review is to describe the current state of knowledge regarding management of BPSD, with a particular focus on agitation...
  100. ncbi Age-dependent pharmacokinetic and pharmacodynamic response in preweanling rats following oral exposure to the organophosphorus insecticide chlorpyrifos
    C Timchalk
    Battelle Pacific Northwest Division, Center for Biological Monitoring and Modeling, 902 Battelle Boulevard, Richland, WA 99352, USA
    Toxicology 220:13-25. 2006
    ..The results suggest that in the preweanling rat, CPF was rapidly absorbed and metabolized, and the extent of metabolism and ChE inhibition was age-dependent...
  101. ncbi Open-label, multicenter, phase 3 extension study of the safety and efficacy of donepezil in patients with Alzheimer disease
    R S Doody
    Department of Neurology, Baylor College of Medicine, 6550 Fannin Street, Suite 1801, Houston, TX 77030-3498, USA
    Arch Neurol 58:427-33. 2001
    ..CONCLUSIONS: Donepezil is an effective and safe drug for the long-term symptomatic treatment of mild to moderately severe AD for up to 144 weeks (2.8 years), and sustained treatment may confer some advantages...

Research Grants63

    KIRTI VALIA; Fiscal Year: 2002
    The FDA has approved two-cholinesterase inhibitors for mild to moderate symptoms of Alzheimer's disease in the tablet dosage form. Both drugs are administered orally, requiring one or more tablets per day to be taken...
  2. Visual Cognition in Dementia with Lewy Bodies
    Joanne M Hamilton; Fiscal Year: 2010
    ..precision is particularly important since DLB patients may demonstrate a heightened response to cholinesterase inhibitors, may be particularly sensitive to neuroleptic medications, and may experience a different clinical ..
  3. Mechanism and Treatment of nerve agent-induced seizures
    Jaideep Kapur; Fiscal Year: 2010
    ..Experiments outlined in Aim 1 seek to confirm and extend the observation that OP cholinesterase inhibitors enhance glutamate release from presynaptic terminals in the hippocampus, using patch clamp ..
  4. Persistent Attenuation of Cocaine-Reinforced Behavior
    KENNETH W GRASING; Fiscal Year: 2013
    ..b>Cholinesterase inhibitors such as tacrine increase synaptic levels of ACh by preventing its inactivation by AChE or BuChE, and can ..
  5. Tacrine Effects on Cocaine Self-Administration and Pharmacokinetic Measures
    KENNETH W GRASING; Fiscal Year: 2012
    ..b>Cholinesterase inhibitors such as tacrine increase synaptic levels of ACh by preventing its inactivation by acetylcholinesterase (..
  6. Repurposing cholinesterase inhibitors for smoking cessation
    REBECCA ASHARE; Fiscal Year: 2013
    ..This comprehensive, interdisciplinary mentored approach will enhance my clinical research skills and my ability to compete successfully for R01 funding and establish an independent program of research. ..
  7. Cholinesterase Inhibitors, Axonal transport, and Memory
    Alvin V Terry; Fiscal Year: 2013
    ..The experiments will contribute to a better understanding of the toxicity associated with a class of chemicals that continues to pose a significant environmental risk to millions of people worldwide. ..
  8. Pope-Presynaptic modulation of anticholinesterase toxicity
    Carey N Pope; Fiscal Year: 2013
    ..This project will evaluate the role of endocannabinoid signaling in the expression of anticholinesterase toxicity and determine whether its differential modulation participates in selective toxicity. ..
  9. The Rosetta Enzyme ReDesign: Targeting PON1 as OP Scavenger
    Jennifer M Bui; Fiscal Year: 2012
    DESCRIPTION (provided by applicant) Many organophosphate (OP) compounds are potent cholinesterase inhibitors and have extensively been used as pesticides and insecticides in agriculture, as a flame retardant in plastics and rubbers, and ..
  10. Cholinesterase Inhibitors in Alzheimer's Disease
    Debomoy K Lahiri; Fiscal Year: 2012
    ..Four of five current FDA-approved drugs for AD are cholinesterase inhibitors (ChEI), which increase the brain's supply of acetylcholine (ACh) by inhibiting cholinesterases (ChE)..
  11. Development of Animal Models of Anti-MuSK Myasthenia
    David P Richman; Fiscal Year: 2011
    ..However, data have accumulated demonstrating that many of these treatments, e.g. cholinesterase inhibitors, thymectomy and immunoglobulin infusion, are minimally effective...
  12. A Neurosteroid-based Novel Treatment for OP-Intoxication
    Doodipala Samba Reddy; Fiscal Year: 2012
    ..Organophosphates (OP) are irreversible cholinesterase inhibitors and OP intoxication following exposure to DFP and related military nerve agents results in persistent ..
    Paul Greengard; Fiscal Year: 2011
    ..Furthermore, we will investigate whether cholinesterase inhibitors affect glutamate receptor localization (Aim II)...
  14. Development of a Novel Therapeutic for Alzheimer'Disease
    MARK ANTHONY LOVELL; Fiscal Year: 2012
    ..two classes of medications are FDA approved for use by Alzheimer's disease (AD) patients including cholinesterase inhibitors (Aricept) and an N-methyl-D-aspartate (NMDA) antagonist (Memantine)...
  15. Citalopram Treatment for Agitation in Alzheimer Dementia
    Constantine G Lyketsos; Fiscal Year: 2012
    ..Several pharmacologic options have been explored, but findings for anticonvulsants, antipsychotics, and cholinesterase inhibitors are disappointing or associated with questionable risk: benefit ratio...
  16. Apathy in Alzheimer's Disease Methylphenidate Trial
    Paul B Rosenberg; Fiscal Year: 2010
    ..Recent studies have begun to explore pharmacologic options, such as cholinesterase inhibitors (ChEIs)...
  17. Deep Brain Stimulation for Alzheimer's Disease
    Constantine G Lyketsos; Fiscal Year: 2013
    ..over one year, in contrast to the natural course of AD, and in excess of the effects of chronic cholinesterase inhibitors. Furthermore, studies in rodents demonstrated that DBS-F leads to improved memory and hippocampal ..
  18. Restoration of Estradiol Effects on Learning by Cholinergic Enhancement
    Robert Gibbs; Fiscal Year: 2009
    ..Based on this, we predict that enhancing the cholinergic system pharmacologically (e.g., via the use of cholinesterase inhibitors) will re-open the window of opportunity and restore responsiveness, even after prolonged loss of ovarian ..
  19. Neural mechanisms of perceptual learning in the human brain
    Michael A Silver; Fiscal Year: 2011
    ..Drugs that prolong the synaptic actions of endogenous acetylcholine (cholinesterase inhibitors) are the most common treatment of Alzheimer's disease...
  20. Spinal Noradrenergic Sprouting after Nerve Injury
    James Eisenach; Fiscal Year: 2012
    ..for analgesia after nerve injury, this pathway could be augmented by norepinephrine transporter and cholinesterase inhibitors. Exciting new preliminary data in humans suggests that the cholinesterase inhibitor, donepezil (Aricept...
  21. Roles and mechanisms of neurotensin in learning and memory
    Saobo Lei; Fiscal Year: 2013
    ..3 million Americans. The current drugs available for the treatment of AD including the cholinesterase inhibitors and the partial NMDA receptor antagonist memantine only benefit a subset of patients for a limited ..
  22. Central Cholinergic System, Its History &Current Status
    ALEXANDER KARCZMAR; Fiscal Year: 2002
    ..Furthermore, of the 10 chapters planned four are prepared and ready for final revision and updating. ..
  23. A Nonisotopic HTS Assay to Elucidate Choline Transporter (CHT) Modulators
    ALICIA RUGGIERO; Fiscal Year: 2009 positively impact cognitive deficits in Alzheimer's Disease (AD) and other dementias are the cholinesterase inhibitors. These prevent the breakdown of the neurotransmitter acetylcholine (ACh), and thus augment Ach function...
  24. Synthesis of Longer-Term Alzheimer Disease Studies in Order to Model and Improve
    Lon S Schneider; Fiscal Year: 2013
    ..Efficacy mainly has been demonstrated in trials of 6 months or less, only with cholinesterase inhibitors for mild AD, and not in MCI or longer-term trials...
  25. Donepezil-enhanced management of delirium in aged hip fracture patients
    Edward Marcantonio; Fiscal Year: 2007
    ..One potential approach to enhance the management of delirium is drug treatment. Cholinesterase inhibitors are now used commonly to improve cognitive function in patients with dementia by enhancing central ..
    John Csernansky; Fiscal Year: 2009
    Treatment with cholinesterase inhibitors is now routine for patients with very mild-to-mild dementia of the Alzheimer type (DAT)...
  27. Cognitive Enhancers Explored with PET Imaging
    Susan Schultz; Fiscal Year: 2003
    ..The therapeutic effects of cholinesterase inhibitors have not yet been definitively mapped to regional changes in cerebral activity, nor have they been ..
  28. Analysis of human cortical networks during sustained visuospatial attention
    Michael Silver; Fiscal Year: 2009
    ..Drugs that prolong the synaptic actions of endogenous acetylcholine (cholinesterase inhibitors) improve performance on attention tasks in human subjects...
    William Messer; Fiscal Year: 1990
    ..Recent advances in the treatment of Alzheimer's disease focus on the use of cholinesterase inhibitors to elevate levels of acetylcholine...
  30. Cholinergic Enhancement of Human Cortical Plasticity
    Bruce Rosen; Fiscal Year: 2003
    ..New drugs, known as cholinesterase inhibitors, that safely and effectively increase ACh levels in humans have recently been developed and FDA-approved...
  31. Estrogenic-cholinergic interactions in memory modulation
    KARYN FRICK; Fiscal Year: 2004
    ..abstract_text> ..
    Charles Thompson; Fiscal Year: 1991
    ..These standards will be used to determine the levels and composition of isomerides in technical material. They will also be used to determine the in vitro potency against acetylcholinesterase and neurotoxic esterase (NTE)...
    Janice Chambers; Fiscal Year: 1990
  34. Neonatal Ethanol-Induced Memory Impairments in Rats
    Pamela Hunt; Fiscal Year: 2009
    ..from one situation to another, while the pharmacological treatments will include acute administration of cholinesterase inhibitors or chronic choline supplementation to the diet of the offspring...
    JOSEPH TOBIN; Fiscal Year: 2000
    ..efficacy in clinical trials, and since nicotinic receptor subtype selective agents and novel cholinesterase inhibitors for systemic administration are under active clinical development for other indications, these studies ..
  36. Muscarinic Receptors in Alzheimer's Disease
    Allan Levey; Fiscal Year: 2009
    ..b>Cholinesterase inhibitors are the main cholinomimetics available for clinical use, but are only modestly effective and frequently ..
    TIMOTHY DELOREY; Fiscal Year: 2000
    ..the drug-induced increase in the activity of cholinergic neurons by the use of muscarinic agonists and cholinesterase inhibitors. A possible reason for this limited success is that an effective strategy is likely to require both ..
  38. Fetal & Adolescent Nicotine Effects on CNS 5HT Systems
    Theodore Slotkin; Fiscal Year: 2003
    ..abstract_text> ..
    Theodore Slotkin; Fiscal Year: 2004
    ..Molecular mechanisms of developmental neurotoxicity can be determined and linked to eventual alterations in behavioral performance. ..
    Theodore Slotkin; Fiscal Year: 2003
  41. Treatment of apathy in Alzheimer's disease with modafinil
    Laura Frakey; Fiscal Year: 2006 will explore the efficacy of modafinil, a psychostimulant medication, used adjunctively with cholinesterase inhibitors (CHIs) in treatment of apathy in AD patients...
  42. Depression in Alzheimer's Disease Study 2 (DIADS-2)
    Lon Schneider; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  43. Frontotemporal degeneration: a basis for clinical trials
    David Knopman; Fiscal Year: 2006
    ..abstract_text> ..
  44. Progestrone and the Effects of Nicotine
    Mehmet Sofuoglu; Fiscal Year: 2006
    ..By characterizing the progesterone effects on nicotine dependence, this study may provide a better understanding of the mechanisms which mediate the sex and menstrual cycle phase effects on nicotine dependence. ..
    Charles Timchalk; Fiscal Year: 2006
    ..It is reasonable to speculate that once this model system has been adequately validated it can readily be employed to screen sensitive populations (e.g. children) that are at greatest risk from chronic Pb exposure. ..
  46. Predictors of Alzheimers Disease in Mild Cognitive Impairment
    Oscar Lopez; Fiscal Year: 2007
    ..g., structural and perfusion MRI, plasma beta-amyloid) and the factors that modify the risk to express the clinical syndrome takes on an added importance. [unreadable] [unreadable] [unreadable] [unreadable]..
    Palmer Taylor; Fiscal Year: 2003
    ..The Centralized Animal Facility is critically needed to support this effort and allow economies of scale for animal research. ..
    Palmer Taylor; Fiscal Year: 2008
    ..abstract_text> ..
  49. Aging and Sites of Action of Cognition-Enhancing Drugs
    DIANA WOODRUFF PAK; Fiscal Year: 2008
    ..These studies will likely support hypotheses about ACh mechanisms in learning and memory and may identify the cerebellum as an additional site of drug action. [unreadable] [unreadable]..
  50. Development of Selective Nanoporous Sorbents for Radionuclide Decorporation
    Charles Timchalk; Fiscal Year: 2008
    ..abstract_text> ..
  51. Mixture Modeling: Pesticide Drug Interactions
    Charles Timchalk; Fiscal Year: 2009
    ..It is fully anticipated that this approach will facilitate the understanding of a variety of complex chemical interactions as it relates to the occupational health implications of working with insecticides. ..
  52. GABA Medications for Tobacco Addiction
    Mehmet Sofuoglu; Fiscal Year: 2009
    ..The findings of this study will provide valuable information to develop new pharmacotherapies for smoking cessation. ..
  53. Nicotinic Receptor Template-guided Drug Design
    Palmer Taylor; Fiscal Year: 2008
    ..The final stages of investigation will include studies in rodents to determine efficacy and toxicity. ..
  54. Cocaine Withdrawal and Pharmacotherapy Response
    Mehmet Sofuoglu; Fiscal Year: 2010
    ..This proposal, by testing the efficacy of carvedilol and investigating the influence of withdrawal severity on carvedilol's efficacy, may result in development of more effective treatments for cocaine addiction. ..
  55. Mechanisms of Associative Learning in Aging: Mouse Models
    Diana S Woodruff Pak; Fiscal Year: 2010
    ..This proposal has the potential to expand perspectives and devise treatments to facilitate learning and memory in older adults. ..
  56. Development of Inventory of Depressive Symptomatology
    PUDUGRAMAM DORAISWAMY; Fiscal Year: 2005
    ..g., anxiety, irritability) (IDS-C and SR) that are in the public domain for use with patients across the age spans seen in practice and in research. ..
    Douglas Galasko; Fiscal Year: 2006
    ..Subproject by Lee: 'PHF-tau in neurodegenerative diseases of Guam' will assess oxidative markers related to brain lesions in ALS, PDC and dementia. ..
  58. Microinfusion Pump For Animal Functional Brain Mapping
    DANIEL HOLSCHNEIDER; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  59. Biomarkers in Aging, MCI and Alzheimer's Disease
    Douglas Galasko; Fiscal Year: 2007
    ..Banked CSF and plasma will be available for further research into novel biomarkers, including broad-based proteomic studies. ..
    DANIEL HOLSCHNEIDER; Fiscal Year: 2001