Do tetrahydroaminoacridine (THA) and physostigmine restore acetylcholine release in Alzheimer brains via nicotinic receptors?
In the presence of 9-amino-1,2,3,4-tetrahydroacridine (THA) 10(-4) M or physostigmine 10(-4) M, the in vitro 3H-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 of 3H-ACh in AD/SDAT brain tissue. This facilitating effect on 3H-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 the 3H-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 with 3H-nicotine, 3H-ACh and 3H-quinuclidinyl benzilate (3H-QNB) as receptor ligands, THA interfered with both nicotinic and muscarinic receptor ligand binding, while physostigmine had much less effect.
Nilsson
L
L
Department of Pharmacology, University of Uppsala, Sweden.
Adem
A
A
Hardy
J
J
Winblad
B
B
Nordberg
A
A
D000109:Acetylcholine / Q000378:metabolism*; D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D000609:Aminoacridines / Q000494:pharmacology*; D003704:Dementia / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010830:Physostigmine / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D013619:Tacrine / Q000494:pharmacology*
D000609:Aminoacridines; D011978:Receptors, Nicotinic; D013619:Tacrine; D010830:Physostigmine; D000109:Acetylcholine