Carbamates with differential mechanism of inhibition toward acetylcholinesterase and butyrylcholinesterase

S Darvesh, KV Darvesh, RS McDonald…

Index: Darvesh, Sultan; Darvesh, Katherine V.; McDonald, Robert S.; Mataija, Diane; Walsh, Ryan; Mothana, Sam; Lockridge, Oksana; Martin, Earl Journal of Medicinal Chemistry, 2008 , vol. 51, # 14 p. 4200 - 4212

Full Text: HTML

Citation Number: 75

Abstract

Most carbamates are pseudoirreversible inhibitors of cholinesterases. Phenothiazine carbamates exhibit this inhibition of acetylcholinesterase but produce reversible inhibition of butyrylcholinesterase, suggesting that they do not form a covalent bond with the catalytic serine. This atypical inhibition is attributable to π− π interaction of the phenothiazine moiety with F329 and Y332 in butyrylcholinesterase. These residues are in a helical segment, ...