Galantamine is an allosterically potentiating ligand of the human alpha 4/beta 2 nAChR

Galantamine (Reminyl(TM)) is a novel drug treatment for mild to moderate Al zheimer's disease (AD). Originally established as a reversible inhibitor of the acetylcholine-degrading enzyme acetylcholinesterase (AChE), galantamin e also acts as an allosterically potentiating ligand (APL) on nicotinic ace tylcholine receptors (nAChR). Having previously established this second mod e of action on nAChRs from murine brain, we demonstrate here the same actio n 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 al l. or most, AChE inhibitors, as is shown by the absence of this effect for other therapeutically applied AChE inhibitors including tacrine, metrifonat e, rivastigmine and donepezil. The possible benefits for therapy of AD of a n APL action on nicotinic receptors is discussed.