Abstract
A well-known hypothesis on the pathophysiology of cognitive dysfunction in patients with Alzheimer’s disease (AD), the “cholinergic hypothesis”, focuses on deficits in various presynaptic components of the cholinergic system of neurotransmission. The following deficits were found in brains of AD patients:
-
a.)
The acetylcholine (ACh) synthesizing enzyme choline acetyltransferase (CAT) is decreased. This enzyme is also a marker for presynaptic neurons.
-
b.)
The high-affinity transport system of choline (Ch) back into the presynaptic neuron is decreased.
-
c.)
The number of cholinergic cell bodies in the subcortical nucleus basalis of Meynert is dramatically decreased in AD brains.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Bruno G, Mohr E, Gillespie M, Fedio P and Chase TN (1986): Muscarinic agonist therapy of Alzheimer’s disease. Arch Neurol 43:659–661.
Caine ED (1980): Cholinomimetic treatment fails to improve memory disorders. New Eng J Med 315:1241–1245.
Christie JE, Shering A, Ferguson J and Glen AIM (1981): Physostigmine and arecoline: effects of intravenous infusions in Alzheimer’s presenile dementia. Br J Psychiatry 138:46–50.
Davis KL Hollander E, Davidson M, Davis BM, Mohs RC and Horvath TB (1987): Induction of depression with oxotremorine in patients with Alzheimer’s disease. Amer J Psychiatry 144:469–471.
Davis KL, Berger PA and Hollister LE (1978): Physostigmine in mania. Arch Gen Psychiatry 35:119–122.
Enz A, Shapiro G, Supavilai P and Boddeke HWGM (1991): SDZ ENS 163 is a selective M1 agonist and induces release of acetylcholine. Naunyn-Schniiedeberg’s Arch Pharmacol (submitted).
Enz A, Lichtsteiner M and Boddeke HWGM (1991): Investigation of AF102B in various models for Ml and M3 muscarinic receptors. Experientia 47:A11.
Fisher A, Brandeis R, Pittel Z, Karton I, Saphir M, Dachir S, Levy A and Heldman E (1989): (+/−)-cis-2-methyl-spiro(l,3-oxathiolane-5,3′)quinuclidine (AF102B): a new Ml agonist attenuates cognitive dysfunctions in AF64A-treated rats. Neurosci Lett 102:325–331.
Harbaugh RE, Roberts DW, Coombs DW, Saunders RL and Reeder TM (1984): Preliminary report: Intracranial cholinergic drug infusion in patients with Alzheimer’s disease. Neurosurgery 15:514–518.
Hollander E, Davidson M, Mohs RC, Horvath TB, Davis BM, Zemeshlany Z and Davis KL (1987): RS 86 in the treatment of Alzheimer’s disease: cognitive and biological effects. Biol Psychiatry 22:1067–1078.
Mash DC, Flynn DD and Potter LT (1985): Loss of M2 muscarine receptors in the cerebral cortex in ALzheimer’s disease and experimental cholinergic denervation. Science 228:1115–1117.
Nakahara N, Fujise N, Kawanishi G and Mizobe F (1990): Central muscarinic activities of an Ml-selective agonist: preferential effects on reversal of amnesia. Brain Res 507:172–175.
Nordstrom Ö, Alberts P, Westlind A, Unden A and Bartfai T (1983): Presynaptic antagonist-postsynaptic agonist at muscarinic cholinergic synapses. N-Methyl-N-(l-methyl-4-pyrrolidino-2-butynyl)acetamide. Mol Pharmacol 24:1–5.
Ogane N, Takada Y, Iga Y, Kawanishi G and Mizobe F (1990): Effects of a Ml muscarinic receptor agonist on the central cholinergic system, evaluated by microdialysis. Neurosci Lett 114:95–100.
Ohtani Y, Murasaki M, Tshii Y, Tshigooka J and Miura S (1990): Phase 1 study of FKS-508 single and multiple dose studies. Eur J Pharmacol 183:1038.
Palacios JM, Bolliger G, Closse A, Enz A, Gmelin G and Malanowski J (1986): The pharmacological assessment of RS 86 (2-ethyl-8-methyl-2,8-diazospiro-[4,5]-decan-l,3-dion hydrobromide) a potent, specific muscarinic cholinergic agonist. Eur J Pharmacol 125:45–62.
Palacios JM, Cortes R, Probst A and Karobath M (1986): Mapping of subtypes of muscarinic receptors in the human brain with receptor autoradiographic techniques. Trends Pharmacol Sci 6:56–60.
Penn RD, Martin EM, Wilson RS, Fox JH and Savoy SM (1988): Intraventricular bethanechol infusion for Alzheimer’s disease: results of doubleblind and escalating dose trials. Neurology 38:219–222.
Perry EK, Tomlinson BE, Blessed GE, Bergmann K, Gibson PH and Perry RH (1978): Correlation of cholinergic abnormalities with senile plaques and mental scores in senile dementia. Brit Med J 2:1457–1459.
Read S (1988): Intracerebroventricular bethanechol: dose and response. In: Current Research in Alzheimer Therapy, Giacobini E and Becker R, eds. New York: Taylor and Francis, pp. 315–324.
Schumacher C, Steinberg R, Kan JP, Michaud JC, Bourguignon JJ, Wermuth CG, Feltz P, Worms P and Biziere K (1989): Pharmacological characterization of the aminopyridazine SR 95639A a selective Ml muscarinic agonist. EurJ Pharmacol 166:139–147.
Sitaram N, Weingartner H and Gillin JC (1978): Human serial learning: enhancement with arecoline and impairment with scopolamine correlated with performance on placebo. Science 201:274–276.
Tariot PN, Cohen RM, Sunderland T and Mellow AM (1988): Multiple-dose arecoline infusion in Alzheimer’s disease. Arch Gen Psychiatry 45:901–905.
Wettstein A and Spiegel R (1984): Clinical trials with the cholinergic drug RS 86 in Alzheimer’s disease and senile dementia of the Alzheimer’s type (SDAT). Psychopharmacology 84:572–573.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1991 Springer Science+Business Media New York
About this chapter
Cite this chapter
Enz, A., Gray, J.A., Spiegel, R. (1991). Muscarinic Agonists for Senile Dementia: Past Experience and Future Trends. In: Becker, R., Giacobini, E. (eds) Cholinergic Basis for Alzheimer Therapy. Advances in Alzheimer Disease Therapy. Birkhäuser, Boston, MA. https://doi.org/10.1007/978-1-4899-6738-1_40
Download citation
DOI: https://doi.org/10.1007/978-1-4899-6738-1_40
Publisher Name: Birkhäuser, Boston, MA
Print ISBN: 978-1-4899-6740-4
Online ISBN: 978-1-4899-6738-1
eBook Packages: Springer Book Archive