Change in the reactivity of the active-site serine OH of butyrylcholinesterase caused by a new reversible inhibitor.
The 2-chloro-12-(2-piperidinoethyl)-dibenzo[d,g] (1,3,6)-dioxazocine . HCl (EGYT-2347), a new specific inhibitor of butyrylcholinesterase inhibits reversibly and non-competitively the enzymatic hydrolysis of butyrylthiocholine iodide (Ki = 0.15 microM, at 37 degrees C in 0.1 M Tris/HCl, pH 7.5). The theoretical progress curve of product accumulation has been developed for the case when a non-competitive reversible inhibitor (EGYT-2347) and an active-site-directed irreversible inhibitor (diisopropylfluorophosphate) act simultaneously. By the aid of this approach it was concluded that the butyrylcholinesterase--EGYT-2347 binary complex does not react with diisopropylfluorophosphate either because of a structural change caused by binding or by the direct steric hindrance of EGYT-2347.
D001665:Binding Sites / Q000187:drug effects; D002800:Cholinesterase Inhibitors; D002802:Cholinesterases; D003989:Dibenzoxazepines / Q000494:pharmacology*; D004347:Drug Interactions; D007531:Isoflurophate / Q000494:pharmacology; D007700:Kinetics
D002800:Cholinesterase Inhibitors; D003989:Dibenzoxazepines; D007531:Isoflurophate; C039088:2-chloro-12-(2-piperidinoethyl)dibenzo(d,g)-1,3,6-dioxazocine; D002802:Cholinesterases