Investigation of the anti-acetylcholinesterase activities of the antimalarial agent, amodiaquine, and related compounds.

The antimalarial agent, amodiaquine, is a potent inhibitor of AChE (Ki = 1.50 x 10(-9) M, pH 7.4, 25 degrees C). Both the protonated diethylamino and phenolic hydroxyl functions of amodiaquine are necessary for interaction with AChE. This suggests that the inhibition of AChE by amodiaquine may involve binding of the protonated diethylamino and phenolic hydroxyl functions to the anionic and esteric sites of the enzyme respectively. The anti-AChE property of amodiaquine may be related in some way to the gastrointestinal and central nervous system disturbances frequently encountered when large doses of amodiaquine are used for the treatment of malaria.