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New Concepts in Alzheimer’s Disease pp 103–121Cite as

Two Drug Binding Sites on Muscarinic Receptors

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Abstract

Neuropathological and biochemical examinations of the brains of patients suffering from senile dementia of the Alzheimer type (SDAT) reveal characterstic abnormalities. These include neurite plaques and neurofibrillary tangles which tend to be localised to the cerebral cortex and hippocampus. In these areas there are also decreased levels of the enzymes and uptake systems present in the nerve terminals which are involved in the synthesis of acetylcholine (for reviews see Bartus et al., 1982; Rossor, 1982; Coyle et al., 1983, 1984; Davies, 1984). In particular, there has been found to be a large reduction in choline-acetyltransferase activity. There is also in SDAT a considerable cell loss in the nucleus basalis of Meynert (Whitehouse et al., 1982; Henke and Lang, 1983). As neurones from this nucleus project to the cerebral cortex and account for an estimated 70% of the cortical content of acetylcholine, it is not surprising that the degeneration of these neurones in SDAT has been assumed to make a contribution to the progression of the disease. It is still not clear whether the primary site of the lesion is in the cell bodies in the basal forebrain or at the cholinergic nerve terminals in the cerebral cortex (Perry et al., 1982; Whitehouse et al., 1982). More importantly, it is not known whether the cholinergic deficit is the primary lesion, as changes in adrenergic, 5-hydroxytryptamine and somatostatin systems have also been observed (for a review, see Rossor and Iversen, 1986).

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Authors
  1. N. J. M. Birdsall
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  2. E. C. Hulme
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  3. W. Kromer
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  4. B. S. Peck
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  5. J. M. Stockton
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  6. M. J. Zigmond
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Editor information

Editors and Affiliations

  1. Département de Pharmacologie Biochimique, Centre de Recherche Pierre Fabre, Avenue Jean Moulin 17, 81100, Castres Cédex, France

    M. Briley

  2. Département de Pharmacologie, Centre Médical Universitaire, 1211, Geneva, Switzerland

    A. Kato

  3. Laboratoire de Pharmacologie et de Toxicologie Fondamentales, Route de Narbonne 205, 31400, Toulouse, France

    M. Weber

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© 1986 The Editors and the Contributors

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Birdsall, N.J.M., Hulme, E.C., Kromer, W., Peck, B.S., Stockton, J.M., Zigmond, M.J. (1986). Two Drug Binding Sites on Muscarinic Receptors. In: Briley, M., Kato, A., Weber, M. (eds) New Concepts in Alzheimer’s Disease. Palgrave, London. https://doi.org/10.1007/978-1-349-08639-9_9

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  • DOI: https://doi.org/10.1007/978-1-349-08639-9_9

  • Publisher Name: Palgrave, London

  • Print ISBN: 978-1-349-08641-2

  • Online ISBN: 978-1-349-08639-9

  • eBook Packages: MedicineMedicine (R0)

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