Substrate activation of butyrylcholinesterase and substrate inhibition of acetylcholinesterase by 3,3-dimethylbutyl-N-n-butylcarbamate and 2-trimethylsilyl-ethyl-N-n-butylcarbamate.

Carbamates are used to treat Alzheimer's disease. These compounds inhibit acetylcholinesterase and butyrylcholinesterase. The goal of this work is to use the substrate analogs of butyrylcholinesterase, 3,3-dimethylbutyl-N-n-butylcarbamate (1) and 2-trimethylsilyl-ethyl-N-n-butylcarbamate (2) to probe the substrate activation mechanism of butyrylcholinesterase. Compounds 1 and 2 are characterized as the pseudo substrate inhibitors of acetylcholinesterase; however, compounds 1 and 2 are characterized as the essential activators of butyrylcholinesterase. Therefore, compounds 1 and 2 mimic the substrate in the acetylcholinesterase-catalyzed reactions, but the behavior of compounds 1 and 2 mimics the substrate activation in the butyrylcholinesterase-catalyzed reactions.