Biomedical papers, 2011 (vol. 155), issue 3

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2011, 155(3):219-223 | 10.5507/bp.2011.036

CHOLINESTERASES, A TARGET OF PHARMACOLOGY AND TOXICOLOGY

Miroslav Pohanka
Faculty of Military Health Sciences, University of Defense, Trebesska 1575, Hradec Kralove, Czech Republic
University Hospital Hradec Kralove, Sokolska 581, Hradec Kralove

Background: Cholinesterases are a group of serine hydrolases that split the neurotransmitter acetylcholine (ACh) and terminate its action. Of the two types, butyrylcholinesterase and acetylcholinesterase (AChE), AChE plays the key role in ending cholinergic neurotransmission. Cholinesterase inhibitors are substances, either natural or man-made that interfere with the break-down of ACh and prolong its action. Hence their relevance to toxicology and pharmacology.

Methods and Results: The present review summarizes current knowledge of the cholinesterases and their inhibition. Particular attention is paid to the toxicology and pharmacology of cholinesterase-related inhibitors such as nerve agents (e.g. sarin, soman, tabun, VX), pesticides (e.g. paraoxon, parathion, malathion, malaoxon, carbofuran), selected plants and fungal secondary metabolites (e.g. aflatoxins), drugs for Alzheimer's disease (e.g. huperzine, metrifonate, tacrine, donepezil) and Myasthenia gravis (e.g. pyridostigmine) treatment and other compounds (propidium, ethidium, decamethonium).

Conclusions: The crucial role of the cholinesterases in neural transmission makes them a primary target of a large number of cholinesterase-inhibiting drugs and toxins. In pharmacology, this has relevance to the treatment of neurodegenerative disorders.

Keywords: Acetylcholinesterase, Butyrylcholinesterase, Alzheimer’s disease, Myasthenia gravis, Huperzine, Donepezil, Rivastigmine, Galantamine

Received: February 24, 2011; Accepted: June 3, 2011; Published: September 1, 2011


References

  1. Loewi O. Uberhumerole ubertragbarkeit der herznervenwirkung. I Mitteilung Pflugers Arch 1921;189:239-42. Go to original source...
  2. Wessler I, Kirkpatrick CJ. Acetylcholine beyond neurons: the non-neuronal cholinergic system in humans. Br J Pharmacol 2008;154:1558-71. Go to original source... Go to PubMed...
  3. Bajgar J. Organophosphates/nerve agent poisoning: mechanism of action, diagnosis, prophylaxis, and treatment. Adv Clin Chem 2004;38:151-216. Go to original source... Go to PubMed...
  4. Manoharan I, Boopathy R, DArvesh S, Lockridge O. A medial health report on individuals with silent butyrylcholinesterase in Vysya community of India. Clin Chim Acta 2007;378:128-35. Go to original source... Go to PubMed...
  5. Li B, Duysen EG, Carlson M, Lockridge O. The butyrylcholinesterase knockout mouse as a model for human butyrylcholinesterase deficiency. J Pharmacol Exp Ther 2008;324:1146-54. Go to original source... Go to PubMed...
  6. Duysen EG, Li B, Lockridge O. The butyrylcholinesterase knockout mouse a research tool in the study of drug sensitivity, biodistribution, obesity and Alzheimers disease. Expert Opin Drug Metab Toxicol 2009;5:523-8. Go to original source... Go to PubMed...
  7. Yen T, Nightingale BN, Burns JC, Sullivan DR, Stewart PM. Butyrylcholinesterase (BCHE) genotyping for post-succinylcholine apnea in an Australian population. Clin Chem 2003;49:1297-1308. Go to original source... Go to PubMed...
  8. Hashim Y, Shepherd D, Wiltshire S, Holman R, Levy JC, Clark A, Cull CA. Butyrylcholinesterase K variant on chromosome 3 q is associated with Type II diabetes in white Caucasian subjects. Diabetologia 2001;44:2227-30. Go to original source... Go to PubMed...
  9. Holmes C, Ballard C, Lehmann D, Smith AD, Beaumont H, Day IN, Khan MN, Lovestone S, McCulley M, Morris CM, Munoz DG, OBrien K, Russ C, Del Ser T, Warden D. Rate of progression of cognitive decline in Alzheimers disease effect of butyrylcholinesterase K gene variation. J Neurol Neurosurg Psychiatry 2005;76:640- 3. Go to original source... Go to PubMed...
  10. Kallow W, Genest K. A method for the detection of human serum cholinesterase: determnation of dibucaine numbers. Can J Biochem 1957;35:339-46. Go to original source... Go to PubMed...
  11. Iwasaki T, Yoneda M, Nakajima A, Terauchi Y. Serum butyrylcholinesterase is strongly associated with adiposity, the serum lipid profile and insulin resistance. Intern Med 2007;46:1633-9. Go to original source... Go to PubMed...
  12. Ostergaard D, Viby-Moogensen J, Hanel HK, Skovgaard LT. Half-life of plasma cholinesterase. Acta Anaesthesiol Scand 1988;32:266-9. Go to original source... Go to PubMed...
  13. Yuan J, Yin J, Wang E. Characterization of procaine metabolism as probe for the butyrylcholinesterase enzyme investigation by simultaneous determination of procaine and its metabolite using capillary electrophoresis with electrochemiluminescence detection. J Chromatogr A 2007;1154:368-72. Go to original source... Go to PubMed...
  14. Zelinski T, Coghlan G, Mauthe J, Triggs-Raine B. Molecular basis of succinylcholine sensitivity in a prairie Hutterite kindred and genetic characterization of the region containing the BCHE gene. Mol Genet Metab 2007;90:210-16. Go to original source... Go to PubMed...
  15. Duysen EG, Li B, Carlson M, Li YF, Wieseler S, Hinrichs SH, Lockridge O. Increased hepatotoxicity and cardiac fibrosis in cocaine-treated butyrylcholinesterase knockout mice. Basic Clin Pharmacol Toxicol 2008;103:514-21. Go to original source... Go to PubMed...
  16. Kolarich D, Weber A, Pabst M, Stadlmann J, Teschner W, Ehrlich H, Schwarz HP, Altmann F. Glycoproteomic characterization of butyrylcholinesterase from human plasma. Proteomics 2008;8:254- 63. Go to original source... Go to PubMed...
  17. Saxena A, Sun W, Luo C, Myers TM, Koplovitz I, Lenz DE, Doctor BP. Bioscavenger for protection from toxicity of organophosphorus compounds. J Mol Neurosci 2006;30:145-8. Go to original source... Go to PubMed...
  18. Rozengart EV, Basova NE, Suvorov AA, Khovanskikh AE. Indophenol chromogenic substrates of cholinesterases of different origin. J Evol Biochem Physiol 2002;38:16-23. Go to original source...
  19. Grigoryan H, Halebyan G, Lefebvre B, Brasme B, Masson P. Mechanism of hydrolysis of dicholine esters with long polymethylene chain by human butyrylcholinesterase. Biochim Biophys Acta 2008;1784:1818-24. Go to original source... Go to PubMed...
  20. Saeed A, de Boeck S, Debruyne I, Wouters J, Stockx J. Hens egg yolk cholinesterase. Purification, characterization and comparison with hens liver and blood plasma cholinesterase. Biochim Biophys Acta 1980;614:389-99. Go to original source... Go to PubMed...
  21. Giacobini E. Cholinesterases: new roles in brain function and in Alzheimers disease. Neurochem Res 2003;28:515-22. Go to original source... Go to PubMed...
  22. Grigoryan HA, Hambardzumyan AA, Mkrtchyan MV, Topuzyan VO, Halebyan GP, Asatryan RS. Alpha, beta-dehydrophenylalanine choline esters, a new class of reversible inhibitors of human acetylcholiensterse and butyrylcholinesterase. Chem Biol Interact 2008;171:108-16. Go to original source... Go to PubMed...
  23. Debord J, Laubarie C, Dantoine T. Microcalorimetric study of the inhibition of butyrylcholinesterase by carbamates. Anal Biochem 2008;373:247-52. Go to original source... Go to PubMed...
  24. Kamal MA, Klein P, Luo W, Li Y, Holloway HW, Tweedie D, Greig NH. Kinetics of human serum butyrylcholinesterase inhibition by a novel experimental Alzheimer therapeutic, dihydrobenzodioxepine cymserine. Neurochem Res 2008;33:745-53. Go to original source... Go to PubMed...
  25. Nagasawa T, Sugisaki H, Tani Y, Ogata K. Purification and characterization of butyrylcholine-hydrolyzing enzyme from Pseudomonas polycolor. Biochim Biophys Acta 1976;429:817-27. Go to original source... Go to PubMed...
  26. Monteiro M, Quintaneiro C, Morgado F, Soares AM, Guilhermino L. Characterization of the cholinesterases present in head tissues of the estuarine fish Pomatoschistus microps: application to biomonitoring. Exotoxicol. Environ. Saf. 2005;62:341-7. Go to original source... Go to PubMed...
  27. Plageman LR, Puletti GM, Skau KA. Characterization of acetylcholinesterase in Caco-2 cells. Exp Biol Med (Maywood) 2002;227:480-6. Go to PubMed...
  28. Zhukovskii YG. On establishment of individuality of the choliensterase enzyme in the studied preparation. J Evol Biochem Physiol 2003;39:281-90. Go to original source...
  29. Blong RM, Bedows E, Lockridge O. Tetramerization domain of human butyrylcholinesterase is at the C-terminus. Biochem J 1997;327:747-57. Go to original source... Go to PubMed...
  30. Lockridge O, Bartels CF, Vaughan TA, Wong CK, Norton SE, Johnson LL. Complete amino acid sequene of human serum cholinesterase. J Biol Chem 1987;262:549-57. Go to PubMed...
  31. Masson P, Nachon F, Bartels CF, Froment MT, Ribes F, Matthews C, Lockridge O. High activity of human butyrylcholinesterase at low pH in the presence of excess butyrylthiocholine. Eur J Biochem 2003;270:315-24. Go to original source... Go to PubMed...
  32. Nicolet Y, Lockridge O, Masson P, Fontecilla-Camps JC, Nachon F. Crystal structure of human butyrylcholinesterase and of its complexes with substrate and products. J Biol Chem 2003;278:41141-7. Go to original source... Go to PubMed...
  33. Fujii T, Mori Y, Tominaga T, Hayasaka I, Kawashima K. Maintenance of constant blood acetylcholine content before and after feeding in young chimpanzees. Neurosci Lett 1997;227:21-4. Go to original source... Go to PubMed...
  34. Fukuto TR. Mechanism of action of organophosphorus and carbamate insecticides. Environ Health Perspect 1990;87:245-54. Go to original source... Go to PubMed...
  35. Vignaud A, Fougerousse F, Mousel E, Guerchet N, Hourde C, Bacou F, Butler-Browne GS, Chatonnet A, Ferry A. Genetic inactivation of acetylcholinesterase causes functional and structural impairment of mouse soleus muscles. Cell Tissue Res 2008;333:289-96. Go to original source... Go to PubMed...
  36. Hartmann J, Kiewert C, Duysen EG, Lockridge O, Greig NH, Klein J. Excessive hippocampal acetylcholine levels in acetylcholinesterase- deficient mice are moderated by butyrylcholinesterase activity. J Neurochem 2007;100:1421-9. Go to original source... Go to PubMed...
  37. Sussman JL, Harel M, Frolow F, Oefner C, Goldman A, Toker L, Silman I. Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein. Science 1991;253:872-9. Go to original source... Go to PubMed...
  38. Ollis DL, Cheah E, Cygler M, Dijkstra B, Frolow F, Franken SM, Harel M, Remington SJ, Silman I, Schrag J, Sussman JL, Verschueren KHG, Goldman A. The / hydrolase fold. Protein Eng 1992;5:197-211. Go to original source... Go to PubMed...
  39. Cygler M, Schrag JD, Sussman JL, Harel M, Silman I, Gentry MK, Doctor BP. Relationship between sequence conservation and three-dimensional structure in a large family of esterases, lipases, and related proteins. Protein Sci 1993;2:366-82. Go to original source... Go to PubMed...
  40. Brenner S. The molecular evolution of genes and proteins: a tale of two serines. Nature 1988;334:528-30. Go to original source... Go to PubMed...
  41. Silman I, Sussman JL. Acetylcholinesterase: how is structure related to function? Chem Biol Interact 2008;175:3-10. Go to original source... Go to PubMed...
  42. Kovarik Z, Radic Z, Berman HA, Simeon-Rudolf V, Reiner E, Taylor P. Acetylcholinesterase active centre and gorge conformations analysed by combinatorial mutations and enantiomeric phosphonates. Biochem J 2003;373:33-40. Go to original source... Go to PubMed...
  43. Bartolucci C, Haller LA, Jardis U, Fels G, Lamba D. Probing Torpedo californica acetylcholinesterase catalytic gorge with two novel bis-functional galanthamine derivatives. J Med Chem 2010;53:745-51. Go to original source... Go to PubMed...
  44. Kreienkamp HJ, Weise C, Raba R., Aaviksaar A, Hucho F. Anionic subsites of the catalytic center of acetylcholinesterase from Torpedo and from cobra venom. Proc Natl Acad Sci USA 1991;88:6117-21. Go to original source... Go to PubMed...
  45. Ripoll DR, Faerman CH, Axelsen PH, Silman I, Sussman JL. An electrostatic mechanism for substrate guidance down the aromatic gorge of acetylcholinesterase. Proc Natl Acad Sci USA 1993;90:5128-32. Go to original source... Go to PubMed...
  46. Koellner G, Steiner T, Millard CB, Silman I, Sussman JL. A neutral molecule in a cation-binding site: specific binding of a PEGSH to acetylcholinesterase from Torpedo californica. J Mol Biol 2002;320:721-5. Go to original source... Go to PubMed...
  47. Changeux JP. Responses of acetylcholinesterase from Torpedo marmarata to salts and curarizing drugs. Mol Pharmacol 1996;2:369- 92. Go to PubMed...
  48. Johnson G, Moore SW. The peripheral anionic site of acetylcholinesterase: structure, functions and potential role in rational drug design. Curr Pharm Des 2006;12:217-25. Go to original source... Go to PubMed...
  49. Haviv H, Wong DM, Silman I, Sussman JL. Bivalent ligands derived from Huperzine A as acetylcholinesterase inhibitors. Curr Top Med Chem 2007;7:375-87. Go to original source... Go to PubMed...
  50. Eichler J, Anselment A, Sussman JL, Massoulie J, Silman I. Differential effects of peripheralsite ligands on Torpedo and chicken acetylcholinesterase. Mol Pharmacol 1994;45:335-40. Go to PubMed...
  51. Inestrosa NC, Dinamarca MC, Alvarez A. Amyloid-cholinesterase interactions. Implications for Alzheimers disease. FEBS J 2008;275:625-32. Go to original source... Go to PubMed...
  52. Chatonnet A, Lockridge O. Comparison of butyrylcholinesterase and acetylcholinesterase. Biochem J 1989;260:625-34. Go to original source... Go to PubMed...
  53. Andres C, elMourabit M, Stutz C, Mark J, Waksman A. Are soluble and membrane-bound rat brain acetlcholinesterase different? Neurochem Res 1990;15:1065-72. Go to original source... Go to PubMed...
  54. Fernandez HL, Moreno RD, Inestrosa NC. Tetrameric (G4) acetylcholinesterase: structure, localization, and physiological regulation. J Neurochem 1996;66:1335-46. Go to original source... Go to PubMed...
  55. Inestrosa NC, Roberts WL, Marshall TL, Rosenberry TL. Acetylcholinesterase from bovine caudate nucleus is attached to membranes by a novel subunit distinct from those of acetylcholinesterases in other tissues. J Biol Chem 1987;262:4441-4. Go to PubMed...
  56. Mehlert A, Varon L, Silman I, Homans SW, Ferguson MAJ. Structure of the glycosyl-phosphatidylinositol membrane anchor of acetylcholinesterase from the electric organ of the electric-fish, Torpedo californica. Biochem J 1993;296:473-9. Go to original source... Go to PubMed...
  57. Rosenberry TL, Roberts WL, Haas R. Glycolipid membrane-binding domain of human erythrocyte acetylcholinesterase. Fed Proc 1986; 45:2970-5. Go to PubMed...
  58. Liao J, Norgaard-Pedersen B, Brodbeck U. Subunit association and glycosylation of acetylcholinesterase from monkey brain. J Neurochem 1993;61:1127-34. Go to original source... Go to PubMed...
  59. Massoulie J, Bon S. The molecular forms of cholinesterse and acetylcholinesterase in verterbrates. Ann Rev Neurosci 1982;5:57-106. Go to original source... Go to PubMed...
  60. Feng G, Krejci E, Molgo J, Cunningham JM, Massoulie J, Sanes JR. Genetic analysis of collagen Q: roles in acetylcholinesterse and butyrylchoilnesterase assembly and in synaptic structure and function. J Cell Biol 1999;144:1349-60. Go to original source... Go to PubMed...
  61. Harel M, Sussman JL, Krejci E, Bon S, Chanal P, Massoulie J, Silman I. Conversion of acetylcholinesterase to butyrylcholinesterase: modeling and mutagenesis. Proc Natl Acad Sci USA 1992;89:10827-31. Go to original source... Go to PubMed...
  62. Haigh JR, Johnston SR, Peppernay A, Mattern PJ, Garcia GE, Doctor BP, Gordon RK, Aisen PS. Protection of red blood cell acetylcholinesterase by oral huperzine A against ex vivo soman exposure: next generation prophylaxis and sequestering of acetylcholinesterase over butyrylcholinesterase. Chem Biol Interact 2008;175:380-6. Go to original source... Go to PubMed...
  63. Ahmed M, Rocha JB, Correa M, Mazzanti CM, Zanin RF, Morschi AL, Morsch VM, Schetinger MR. Inhibition of two different cholinesterases by tacrine. Chem Biol Interact 2006;162:165-71. Go to original source... Go to PubMed...
  64. Pohanka M, Jun D, Kuca K. Amperometric biosensor for evaluation of competitive cholinesterase inhibition by the reactivator HI-6. Anal Lett 2007;40:2351-9. Go to original source... Go to PubMed...
  65. Pohanka M, Musilek K, Kuca K. Progress of biosensors based on cholinesterase inhibition. Curr Med Chem 2009;16:1790-8. Go to original source... Go to PubMed...
  66. Bartling A, Worek F, Szinicz L, Thiermann H. Enzyme-kinetic investigation of different sarin analogues reacting with human acetylcholinesterase and butyrylcholinesterase. Toxicology 2007;233:166-72. Go to original source... Go to PubMed...
  67. Tecles F, Ceron JJ. Determination of whole blood cholinesterase in different animal species using specific substrates. Res Vet Sci 2001;70:233-8. Go to original source... Go to PubMed...
  68. Rosenberry TL. Catalysis by acetylcholinesterase: evidence that the rate-limitng step for acylation with certain substrates general acid-base catalysis. Proc Natl Acad Sci USA 1975;72:3834-8. Go to original source... Go to PubMed...
  69. Krupka RM. The mechanism of action of acetylcholinesterase: substrate inhibition and the binding of inhibitors. Biochemistry 1963;2:76-82. Go to original source... Go to PubMed...
  70. Reed MC, Lieb A, Nijhout HF. The biological significance of substrate inhibition: a mechanism with diverse functions. Bioassays 2010;32:422-9. Go to original source... Go to PubMed...
  71. Guedes RN, Zhu KY, Kambhampati S, Dover BA. Characterization of acetylcholinesterase purified from the lesser grain borer, Rhyzopertha dominica (Coleoptera: Bostrichidae). Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 1998;119:205-10. Go to original source... Go to PubMed...
  72. Gao JR, Zhu KY. An acetylcholinesterase purified from the greenbug (Schizaphis graminum) with some unique enzymological and pharmacological characteristics. Insect Biochem Mol Biol 2001;31:1095-104. Go to original source... Go to PubMed...
  73. Paraoanu LE, Layer PG. Acetylcholinesterase in cell adhesion, neurite growth and network formation. FEBS J 2008;275:618-24. Go to original source... Go to PubMed...
  74. Johnson G, Swart C, Moore SW. Non-enzymatic developmental functions of acetylcholiensterase the question of redundancy. FEBS J 2008;275:519-38. Go to original source... Go to PubMed...
  75. Adler M, Filbert MG. Role of butyrylcholinesterase in canine tracheal smooth muscle function. FEBS Lett 1990;267:107-10. Go to original source... Go to PubMed...
  76. Villarroya M, Garcia AG, Marco JL. New classes of AChE inhibitors with additional pharmacological effects of interests for the treatment of Alzheimers disease. Curr Pharm Des 2004;10:3177-84. Go to original source... Go to PubMed...
  77. Giacobini E. Selective inhibitors of butyrylcholinesterase: a valid alternative for therapy of Alzheimers disease? Drugs Aging 2001;18:891-8. Go to original source... Go to PubMed...
  78. Giacobini E. Cholinesterase inhibitors: new roles and therapeutic alternatives. Pharmacol Res 2004;50:433-40. Go to original source... Go to PubMed...
  79. Weiner L, Shnyrov VL, Konstantinovskji L, Roth E, Ashani Y, Silman I. Stabilization of Torpedo californica acetylcholinesterase by reversible inhibitors. Biochemisty 2009;48:563-74. Go to original source... Go to PubMed...
  80. Millard CB, Kryger G, Ordentlich A, Greenblatt HM, Harel M, Raves ML, Segall Y, Barak D, Shafferman A, Silman I, Sussman JL. Crystal structures of aged phosphonylated acetylcholinesterase: nerve agent reaction products at the atomic level. Biochemistry 1999;38:7032-9. Go to original source... Go to PubMed...
  81. Barak D, Ordentlich A, Stein D, Yu QS, Greig NH, Shafferman A. Accomodation of physostigmine and its analogues by acetylchoilnesterase is dominated by hydrophobic interactions. Biochem J 2009;417:213-22. Go to original source... Go to PubMed...
  82. Schaltz F. Neurosciences and research on chemical weapons of mass destruction in Nazi Germany. J Hist Neurosci 2006;15:186- 209. Go to original source... Go to PubMed...
  83. Kuca K, Pohanka M. Chemcial warfare agents. EXS 2010; 100:543-58. Go to PubMed...
  84. Jovanovic D. The effect of bispyridinium oximes on neuromuscular blockade induced by highly toxic organohposhates in rat. Archives Internationales de Pharmacodynamie et de Therapie 1983;262:231-41. Go to PubMed...
  85. Brimblecomb RW, Green DM, Stratton JA, Thompson PB. The protective actions of some anticholinergic drugs in sarin poisoning. Brit J Pharmacol 1970;39:822-30. Go to original source...
  86. Boskovic B, Kovacevic V, Jovanovic D. 2-PAM chloride HI6 and HGG12 in soman and tabun poisoning. Fund Appl Toxicol 1984;4:106-15. Go to original source... Go to PubMed...
  87. Rengstorff RH. Accidental exposure to sarin: vision effects. Arch Toxicol 1985;56:201-3. Go to original source... Go to PubMed...
  88. Chilcott RP, Dalton CH, Hill I, Davison CM, Blohm KL, Clarkson ED, Hamilton MG. In vivo skin absorption and distribution of the nerve agent VX (O-ethyl-S-[2(diisopropylamino)ethyl] methylphosphonothioate) in the domestic white pig. Hum Exp Toxicol 2005;24:347-52. Go to original source... Go to PubMed...
  89. Hemmer AC, Otto TC, Wierdl M, Edwards CC, Fleming CD, MacDonald M, Cashman JR, Potter PM, Cerasoli DM, Redinbo MR.. Human carboxylesterase 1 stereoselectively binds the nerve agents cyclosarin and spontaneously hydrolyzes the nerve agent sarin. Mol Pharmacol 2010;77:508-16. Go to original source... Go to PubMed...
  90. Kanamori-Kataoka M, Seto Y. Paraoxonase activity against nerve gases measured by capillary electrophoresis and characterization of human serum paraoxonase (PON1) polymorphism in the coding region (Q192R). Anal Biochem 2009;385:94-100. Go to original source... Go to PubMed...
  91. Kasagami T, Miyamoto T, Yamamoto I. Activated transformations of organophoshorus insecticides in the case of non-AChE inhibitory oxons. Pest Manag Sci 2002;58:1107-17. Go to original source... Go to PubMed...
  92. Haigh JR, Adler M, Apland JP, Desphpande SS, Barham CB, Desmond P, Koplovitz I, Lenz DE, Gordon RK. Protection by pyridostigmine bromide of marmoset hemi-diaphragm acetylcholinesterase activity after soman exposure. Chem Biol Interact, In press.
  93. Andersen JB, Engeland A, Owe JF, Gilhus NE. Myasthenia gravis requiring pyridostigmine treatment in a national population cohort. Eur J Neurol, In press.
  94. Darvesh S, Darvesh KV, McDonald RS, Mataija D, Walsh R, Mothana S, Lockridge O, Martin E. Carbamates with differential mechanism of inhibition toward acetylchoilnesterase and butyrylcholinesterase. J Med Chem 2008;51:4200-12. Go to original source... Go to PubMed...
  95. Friedman A, Kaufer D, Shemer J, Hendler I, Soreq H, Tur-Kaspa I. Pyridostigmine brain penetration under stress enhances neuronal excitability and induces early immediate transcriptional response. Nat Med 1996;2:1382-5. Go to original source... Go to PubMed...
  96. Chitnis S, Rao J. Rivastigmine in Parkinsons disease dementia. Expert Opin Drug Metab Toxicol 2009;5:941-55. Go to original source... Go to PubMed...
  97. Cummings JL, Nadel A, Masterman D, Cyrus PA. Efficacy of metrifonate in imporving the psychiatric and behavioral disturbances of patients with Alzheimers disease. J Geriatr Psychiatry Neurol 2001;14:101-8. Go to original source... Go to PubMed...
  98. Alfirevic A, Mills T, Carr D, Barratt BJ, Jawaid A, Sherwood J, Smith JC, Tugwood J, Hartkoorn R, Owen A, Park KB, Pirmohamed M. Tacrine-induced liver damage: an analysis of 19 candidate genes. Pharmacogenet Genomics 2007;17:1091-100. Go to original source... Go to PubMed...
  99. Tumiatti V, Minarini A, Bolognesi ML, Milelli A, Rosini M, Melchiorre C. Tacrine derivatives and Alzheimers disease. Curr Med Chem 2010;17:1825-38. Go to original source... Go to PubMed...
  100. Bajgar J, Bisso GM, Michalek H. Differential inhibition of rat brain acetylcholinesterase molecular forms by 7-methoxytacrine in vitro. Toxicol Lett 1995;80:109-14. Go to original source... Go to PubMed...
  101. Pohanka M, Kuca K, Kassa J. New performance of biosensor technology for Alzheimers disease drugs: in vitro comparison of tacrine and 7-methoxytacrine. Neuroendocrinol Lett 2008;29:755- 8. Go to PubMed...
  102. Jung HA, Min BS, Yokozawa T, Lee JH, Kim YS, Choi JS. Anti- Alzheimer and antioxidant activities of Coptidis Rhizoma alkaloids. Biol Pharm Bull 2009;32:1433-8. Go to original source... Go to PubMed...
  103. Mashkovsky MD, Kruglikova-Lvova RP. On the pharmacology of the new alkaloid galantamine. Farmakologia Toxicologia (Moscow) 1951;14:27-30.
  104. Bartolucci C, Perola E, Pilger C, Fels G, Lamba D. Threedimensional structure of a complex of galanthamine (Nivalin) with acetylcholinesterase from Torpedo californica: implications for the design of new anti-Alzheimer drugs. Proteins 2001;42:182- 91. Go to original source... Go to PubMed...
  105. Pilger C, Bartolucci C, Lamba D, Tropsha A, Fels G. Accurate prediction fo the bound conformation of galanthamine in the active site of Torpedo californica acetylcholinesterase using molecular docking. J Mol Graph Model 2001;19:288-96. Go to original source... Go to PubMed...
  106. Axelsen PH, Harel M, Silman I, Sussman JL. Structure and dynamics of the active site gorge of acetylcholinesterase: synergistic use of molecular dynamics simulation and X-ray crystallography. Protein Sci 1994;3:188-97. Go to original source... Go to PubMed...
  107. Riker WF, Okamoto M, Artusio JF. In vivo reversal of depolarizing neuromuscular blockade. Arch Int Pharmacodyn Ther 1995;330:90-101. Go to PubMed...
  108. Castro A, Martinez A. Targeting beta-amyloid pathogenesis through acetylchoinesterase inhibitors. Curr Pharm Des 2006;12:4377-87. Go to original source... Go to PubMed...
  109. Hansmann T, Sanson B, Stojan J, Weik M, Marty JL, Fournier D. Kinetic insight into the mechanism of cholinesterase inhibition by aflatoxin B1 to develop biosensors. Biosens Bioelectron 2009;24:2119-24. Go to original source... Go to PubMed...
  110. Pohanka M, Musilek K, Kuca K. Evaluation of aflatoxin B1 acetylcholinesterase dissociation kinetic using the amperometric biosensor technology: prospect for toxicity mechanism. Protein Pept Lett 2010;17:340-2. Go to original source... Go to PubMed...
  111. Pohanka, M, Kuca K, Jun D. Aflatoxin assay using an amerometric sensor strip and acetylcholinesterase as recognition element. Sens Lett 2008;6:450-3. Go to original source... Go to PubMed...
  112. Egbunike GN, Ikegwuonu FI. Effect of aflatoxicosis on acetylcholinesterse activity in the brain and adenohypophysis of the male rat. Neurosci Lett 1984;52:171-4. Go to original source... Go to PubMed...
  113. Cavalli A, Bottegoni G, Raco C, De Vivo M, Recanatini M. A computational study of the binding of propidium to the peripheral anionic site of human acetylcholinesterase. J Med Chem 2004;47:3991-9. Go to original source... Go to PubMed...
  114. Mazzanti CM, Spanevello RM, Obregon A, Pereira LB, Streher CA, Ahmed M, Mazzanti A, Graca DL, Morsch VM, Schetinger MR. Ethidium bromide inhibits rat brain acetylcholinesterase activity in vitro. Chem Biol Interact 2006;162:121-7. Go to original source... Go to PubMed...
  115. Drago D, Bolognin S, Zatta P. Role of metal ions in the abeta oligomerization in Alzheimers disease and in other neurological disorders. Curr Alzheimer Res 2008;5:500-7. Go to original source... Go to PubMed...
  116. Jansson ET. Aluminum exposure and Alzheimers disease. J Alzheimers Dis 2001;3:541-9. Go to PubMed...
  117. Kaizer RR, Correa MC, Spanevello RM, Morsch VM, Mazzanti CM, Goncalves JF, Schetinger MR. Acetylcholinesterase activation and enhanced lipid peroxidation after long-term exposure to low levels of aluminum on different mouse brain regions. J Inorg Biochem 2005;99:1865-70. Go to original source... Go to PubMed...
  118. Kaizer RR, Correa MC, Gris LR, da Rosa CS, Bohrer D, Morsch VM, Schetinger MR. Effect of long-term exposure to aluminum on the acetylcholinesterase activity in the central nervous system and erythrocytes. Neurochem Res 2008;33:2294-2301. Go to original source... Go to PubMed...
  119. Inestrosa NC, Perez CA, Simpfendorfer RW. Sensitivity of acetylcholinesterase molecular forms to inhibition by high MgCl2 concentration. Biochim Biophys Acta 1994;1208:286-93. Go to original source... Go to PubMed...
  120. Arce MP, Rodriguez-Franco MI, Gonzalez-Munoz GC, Perez C, Lopez B, Villaroya M, Lopez MG, Garcia AG, Conde S. Neuroprotective and cholinergic properties of multifunctional glutamic acid derivatives for the treatment of Alzeheimers disease. J Med Chem 2009;52:7249-57. Go to original source... Go to PubMed...
  121. Berson A, Knobloch M, Hanan M, Diamant S, Sharoni M, Schuppli D, Geyer BC, Ravid R, Mor TS, Nitsch RM, Soreg H. Changes in readthrough acetylcholinesterase expression modulate amyloid-beta pathology. Brain 2008;131:109-19. Go to original source... Go to PubMed...
  122. Darreh-Shori T, Soininen H. Effects of cholinesterse inhibitors on the activities and protein levels of cholinesterases in the cerebrospinal fluid of patients with Alzheimers disease: a review of recent clinical studies. Curr Alzheimer Res 2010;7:67-73. Go to original source... Go to PubMed...
  123. Gao X, Zheng CY, Yang L, Tang XC, Zhang HY. Huperzine A protects isolated rat brain mitochondria against beta-amyloid peptide. Free Radic Biol Med 2009; 46:1454-62. Go to original source... Go to PubMed...
  124. Zhang HY, Tang XC. Huperzine B, a novel acetylcholinesterase inhibitor, attenuates hydrogen peroxide induced injury in PC12 cells. Neurosci Lett 2000;292:41-44. Go to original source... Go to PubMed...
  125. Bai D. Development of huperzine A and B for treatment of Alzheimers disease. Pure Appl Chem 2007;79:469-79. Go to original source...
  126. Kryger G, Silman I, Sussman JL. Three-dimensional structure of a complex of E2020 with acetylcholinesterase from Torpedo californica. J Physiol Paris 1998;92:191-4. Go to original source... Go to PubMed...