Galantamine is an allosterically potentiating ligand of the human α4/β2 nAChR
M. Samochocki
Laboratory of Molecular Neurobiology, Institute of Physiological Chemistry and Pathobiochemistry, Johannes-Gutenberg University Medical School, D-55,099 Mainz/Germany,
Search for more papers by this authorM. Zerlin
Laboratory of Molecular Neurobiology, Institute of Physiological Chemistry and Pathobiochemistry, Johannes-Gutenberg University Medical School, D-55,099 Mainz/Germany,
Search for more papers by this authorR. Jostock
Laboratory of Molecular Neurobiology, Institute of Physiological Chemistry and Pathobiochemistry, Johannes-Gutenberg University Medical School, D-55,099 Mainz/Germany,
Search for more papers by this authorP. J. Groot Kormelink
Department of Advanced Bio-Technologies, Janssen Research Foundation, B-2340 Beerse/Belgium,
Search for more papers by this authorW.H. M. L. Luyten
Department of Advanced Bio-Technologies, Janssen Research Foundation, B-2340 Beerse/Belgium,
Search for more papers by this authorE. X. Albuquerque
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD 21,201, USA
Search for more papers by this authorA. Maelicke
Laboratory of Molecular Neurobiology, Institute of Physiological Chemistry and Pathobiochemistry, Johannes-Gutenberg University Medical School, D-55,099 Mainz/Germany,
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD 21,201, USA
Search for more papers by this authorM. Samochocki
Laboratory of Molecular Neurobiology, Institute of Physiological Chemistry and Pathobiochemistry, Johannes-Gutenberg University Medical School, D-55,099 Mainz/Germany,
Search for more papers by this authorM. Zerlin
Laboratory of Molecular Neurobiology, Institute of Physiological Chemistry and Pathobiochemistry, Johannes-Gutenberg University Medical School, D-55,099 Mainz/Germany,
Search for more papers by this authorR. Jostock
Laboratory of Molecular Neurobiology, Institute of Physiological Chemistry and Pathobiochemistry, Johannes-Gutenberg University Medical School, D-55,099 Mainz/Germany,
Search for more papers by this authorP. J. Groot Kormelink
Department of Advanced Bio-Technologies, Janssen Research Foundation, B-2340 Beerse/Belgium,
Search for more papers by this authorW.H. M. L. Luyten
Department of Advanced Bio-Technologies, Janssen Research Foundation, B-2340 Beerse/Belgium,
Search for more papers by this authorE. X. Albuquerque
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD 21,201, USA
Search for more papers by this authorA. Maelicke
Laboratory of Molecular Neurobiology, Institute of Physiological Chemistry and Pathobiochemistry, Johannes-Gutenberg University Medical School, D-55,099 Mainz/Germany,
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD 21,201, USA
Search for more papers by this authorAbstract
Galantamine (ReminylTM) 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 α4/β2 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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