Journal of Neural Transmission

, Volume 70, Issue 3–4, pp 357–368

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

  • L. Nilsson
  • A. Adem
  • J. Hardy
  • B. Winblad
  • A. Nordberg
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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.

Key words

Alzheimer's disease 3H-Acetylcholine release THA physostigmine nicotinic receptors muscarinic receptors receptor subtypes 

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Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • L. Nilsson
    • 1
  • A. Adem
    • 1
  • J. Hardy
    • 2
  • B. Winblad
    • 3
  • A. Nordberg
    • 1
  1. 1.Department of PharmacologyUniversity of UppsalaUppsalaSweden
  2. 2.Department of BiochemistrySt. Mary's Hospital Medical SchoolLondonUK
  3. 3.Department of Geriatric Medicine, Karolinska InstituteHuddinge HospitalSweden

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