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Do tetrahydroaminoacridine (THA) and physostigmine restore acetylcholine release in Alzheimer brains via nicotinic receptors?

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Summary

In the presence of 9-amino-1, 2, 3,4-tetrahydroacridine (THA) 10−4M or physostigmine 10−4 M, the in vitro3H-Acetylcholine (3H-ACh) release from control cortical slices was significantly reduced. In contrast, THA 10−4 M and physostigmine 10−4 M significantly increased the release of3H-ACh in AD/SDAT brain tissue. This facilitating effect on3H-ACh release was partially blocked (50%) in the presence of the nicotinic antagonist d-tubocurarine 10−6 M indicating a possible interaction via nicotinic receptors. The muscarinic antagonist atropine 10−5 M significantly increased the3H-ACh release both in control and AD/SDAT brains, thus indicating preservation of muscarinic autoreceptors in the AD/SDAT cortical tissue. In receptor competition studies with3H-nicotine,3H-ACh and3H-quinuclidinyl benzilate (3H-QNB) as receptor ligands, THA interfered with both nicotinic and muscarinic receptor ligand binding, while physostigmine had much less effect.

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Author notes

  1. L. Nilsson

    Present address: Department of Pharmacology, University of Uppsala, Uppsala, Sweden

Authors and Affiliations

  1. Department of Pharmacology, University of Uppsala, Uppsala, Sweden

    A. Adem & A. Nordberg

  2. Department of Biochemistry, St. Mary's Hospital Medical School, London, UK

    J. Hardy

  3. Department of Geriatric Medicine, Karolinska Institute, Huddinge Hospital, Sweden

    B. Winblad

Authors
  1. L. Nilsson
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  2. A. Adem
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  3. J. Hardy
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  4. B. Winblad
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  5. A. Nordberg
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Nilsson, L., Adem, A., Hardy, J. et al. Do tetrahydroaminoacridine (THA) and physostigmine restore acetylcholine release in Alzheimer brains via nicotinic receptors?. J. Neural Transmission 70, 357–368 (1987). https://doi.org/10.1007/BF01253610

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  • DOI: https://doi.org/10.1007/BF01253610

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