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

Abstract

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.