Galantamine is an allosterically potentiating ligand of the human alpha4/beta2 nAChR.
Samochocki M, Zerlin M, Jostock R, Groot Kormelink PJ,
Luyten WH, Albuquerque EX, Maelicke A.
Laboratory of Molecular Neurobiology,
Institute of Physiological Chemistry and Pathobiochemistry, Johannes-Gutenberg University Medical School, Mainz/Germany.
Acta Neurol Scand Suppl 2000;176:68-73
Galantamine (Reminyl) is a novel drug treatment for mild to moderate Alzheimer’s disease (AD). Originally established as a reversible inhibitor of the acetylcholine-degrading enzyme acetylcholinesterase (AChE), galantamine also acts as an allosterically potentiating ligand (APL) on nicotinic acetylcholine receptors (nAChR). Having previously established this second mode of action on nAChRs from murine brain, we demonstrate here the same action of galantamine on the most abundant nAChR in the human brain, the alpha4/beta2 subtype. This nAChR-sensitizing action is not a common property of all, or most, AChE inhibitors, as is shown by the absence of this effect for other therapeutically applied AChE inhibitors including tacrine, metrifonate, rivastigmine and donepezil. The possible benefits for therapy of AD of an APL action on nicotinic receptors is discussed.
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