Elsevier

Neuroscience Letters

Volume 88, Issue 3, 7 June 1988, Pages 281-285
Neuroscience Letters

Effects of tetrahydroaminoacridine on M1 and M2 muscarine receptors

https://doi.org/10.1016/0304-3940(88)90224-8Get rights and content
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Abstract

Tetrahydroaminoacridine (THA) has been reported to improve the memory of persons with Alzheimer's disease, but its mechanism of action is uncertain. We found that clinically effective concentrations, 0.03–0.3 μM, readily inhibit acetylcholinesterase and butyrylcholinesterase from rabbit hippocampal tissue in artificial cerebrospinal fluid (CSF) at 37°C with physiological levels of substrate. Above 1 μM, THA was found to act at primary and allosteric sites on M1 and M2 muscarine receptors as an antagonist. This is not clinically important, and low levels of THA do not improve the binding of the agonist, oxotremorine-M. Only 10–1000 μM THA has been shown to block K+ channels. Thus THA probably acts as an esterase inhibitor.

Keywords

Tetrahydroaminoacridine
Alzheimer's disease
Acetylcholinesterase
Allosterism
Muscarine receptor
Antagonist

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