Pharmacological Activity of Novel Anticholinesterase Agents of Potential Use in the Treatment of Alzheimer’s Disease

  • Marta Weinstock
  • Michal Razin
  • Michael Chorev
  • Zeev Tashma
Part of the Advances in Behavioral Biology book series (ABBI, volume 29)


In dementia of the Alzheimer type there is a selective loss in the cerebral cortex of choline acetyltransferase (CAT), the enzyme that synthesizes acetylcholine (ACh)1,2. The degree of dementia and memory impairment that occurs in this condition is well correlated with the decrement in cortical cholinergic transmission3. Moreover, scopolamine, a cholinergic antagonist, can cause memory impairment in normal individuals similar to that in aging4. These findings suggest that impaired cortical cholinergic transmission may be at least in part responsible for the symptomatology of Alzheimer disease. In support of this suggestion it was found that physostigmine, which prevents the destruction of ACh, can cause memory improvement in Alzheimer patients5. The extent of improvement of the symptomatology was closely related to the degree of inhibition of acetylcholinesterase (AChE) in the spinal fluid, and thus to the amount of physostigmine reaching the central nervous system6.


AChE Activity Corpus Striatum Brain AChE Phenyl Carbamate Choline Acetyl Transferase 
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  1. 1.
    P. Davies, and A.J.F. Maloney,Selective loss of central cholinergic neurons in Alzheimer’s disease, Lancet 2: 1403 (1976).PubMedCrossRefGoogle Scholar
  2. 2.
    J.A. Richter, E.K. Perry, and E.B. Tomlinson, Acetylcholine and choline levels in post-mortem human brain tissue: preliminary observations in Alzheimer’s disease, Life Sci., 26: 1683 (1980).PubMedCrossRefGoogle Scholar
  3. 3.
    E.K. Perry, B.E. Tomlinson, G. Blessed, K. Bergmann, P.H. Gibson, and R.H. Perry, Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia, Br. Med. J., 2: 1457 (1979).CrossRefGoogle Scholar
  4. 4.
    D.A. Drachman, and J.B. Leavitt, Human memory and the cholinergic system, Arch. Neurol., 30: 113 (1974).PubMedGoogle Scholar
  5. 5.
    K.L. Davis, R.C. Mohs, and J.R. Tinklenberg, Enhancement of memory by physostigmine, N. Engl. J. Med., 301: 946 (1979).PubMedGoogle Scholar
  6. 6.
    L.J. Thai, P.A. Fuld, M.S. Masur, and N.S. Sharpless, Oral physostigmine and lecithin improve memory in Alzheimer’s disease, Ann. Neurol., 13: 491 (1983).CrossRefGoogle Scholar
  7. 7.
    K.L. Davis, and R.C. Mohs, Enhancement of memory processes in Alzheimer’s disease with multiple-dose intravenous physostigmine, Am. J. Psychiat., 139: 1421 (1982).PubMedGoogle Scholar
  8. 8.
    E. Stedman, Studies on the relationship between chemical constitution and physiolgical action. I. Position isomerism in relation to miotic activity of synthetic methanes. Biochem. J. 20: 719 (1926).PubMedGoogle Scholar
  9. 9.
    B.H. Peters, and H.S. Levin, Effects of physostigmine and lecithin on memory in Alzheimer’s disease. Ann. Neurol. 6: 219 (1979).PubMedCrossRefGoogle Scholar
  10. 10.
    A.R. Main, Mode of action of anticholinesterases. Pharmacol. Therap. 6: 579 (1979).CrossRefGoogle Scholar
  11. 11.
    E. Stedman, and E. Stedman, Methyl urethans of the isomeric h hydroxyphenylethyldimethylamines and their miotic activity. J. Chem. Soc. 609 (1929).Google Scholar
  12. 12.
    J. Meltsep, and O.A. Welle, Wc-tiddai activity of substituted phenyl N-methyl carbamates. Entomol. Exp. Appl. 12: 169 (1969).CrossRefGoogle Scholar
  13. 13.
    G.L. Ellman, K.D. Courtney, V. Andres Jr., and R.M. Featherstone, A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 7: 88 (1961).PubMedCrossRefGoogle Scholar
  14. 14.
    A. Herz, H. Teschamacher, A. Hofstetter, and K. Kurg, Importance of lipid solubility for the central action of cholinolytic drugs. Int. J. Neuropharmacol. 4, 207 (1965).PubMedCrossRefGoogle Scholar
  15. 15.
    X. Machne, and K.W.R. Unna, Actions at the central nervous system, in: “Cholinesterases and Anticholinesterase Agents”, G.B. Koelle, ed., Springer-Verlag, Berlin (1963).Google Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Marta Weinstock
    • 1
  • Michal Razin
    • 1
  • Michael Chorev
    • 2
  • Zeev Tashma
    • 2
  1. 1.Departments of Pharmacology School of PharmacyHebrew UniversityJerusalemIsrael
  2. 2.Medicinal Chemistry School of PharmacyHebrew UniversityJerusalemIsrael

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