Cholinesterase Inhibitors: An Overview of their Mechanisms of Action

  • Albert Enz
  • Philipp Floersheim
Part of the Advances in Alzheimer Disease Therapy book series (AADT)

Abstract

Alzheimer’s disease (AD) is a degenerative disorder of the CNS which will become a major health problem in the following decades. AD is associated with a decrease of cholinergic activity in the cortex and other brain regions. Of the different approaches to reversing the cholinergic deficit, the inhibition of acetylcholinesterase (AChE) seems to produce symptomatic improvements in clinical trials (Whitehouse, 1993).

Keywords

Hydrolysis Benzene Dementia Adduct Serine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Becker RE, Colliver J, Elble R, Feldman E, Giacobini E, Kumar V, Markwell S, Moriearty P, Parks R, Shillcutt SD, Unni L, Vicary S, Womack C and Zee RF (1990): Effect of Metrifonate, a long-acting cholinesterase inhibitor in Alzheimer’s disease. Drug Dev Res 19:425–434.CrossRefGoogle Scholar
  2. Enz A, Amstutz R, Boddeke H, Gmelin G and Malanowsky J (1993): Brain selective inhibiton of acetylcholinesterase: a novel approach to therapy for Alzheimer’s disease. In: Cholinergic Function and Dysfunction, Progress in Brain Research Vol 98. Cuello AC, ed. Amsterdam, Elsevier Science Publisher, pp 431–438.CrossRefGoogle Scholar
  3. Hallak M and Giacobini E (1987): A comparison of the effects of two inhibitors on brain cholinersterase. Neuropharmacol 26:521–530.CrossRefGoogle Scholar
  4. Harel M, Schalk I, Ehrat-Sabatier L, Bouet F, Goeldner M, Hirth C, Axelsen PH, Silman I and Sussman JL (1993): Quaternary ligand binding to aromatic residues in the active-site gorge of acetylcholinesterase. Proc Nat Acad Sci 90:9031–9035.PubMedCrossRefGoogle Scholar
  5. Nordgren I, Bergstroem M, Holmstedt B and Sandoz M (1978): Transformation and action of metrifonate. Arch Toxicol 41:31–41.PubMedCrossRefGoogle Scholar
  6. Quinn DM (1987): Acetylcholinesterase: Enzyme structure, reaction dynamics, and virtual transition states. Chem Rev 87:955–979.CrossRefGoogle Scholar
  7. Spaldin V, Maddan S, Pool WF, Woolf TF and Park K (1994): The effect of enzyme inhibition on the metabolism and activation of tacrine by human liver microsomes. Br J Pharmac 38:15–22.Google Scholar
  8. Sussman JL, Harel M, Frolow F, Oefner C, Toker L and Silman I (1991): Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein. Science 253:872–879.PubMedCrossRefGoogle Scholar
  9. Whitehouse PJ (1993): Cholinergic therapy in dementia. Acta Neurol Scand (Supp.) 149:42–45.Google Scholar

Copyright information

© Birkhäuser Boston 1997

Authors and Affiliations

  • Albert Enz
    • 1
  • Philipp Floersheim
    • 1
  1. 1.Preclinical ResearchSandoz Pharma Ltd.BaselSwitzerland

Personalised recommendations