1(2-benzoylethyl)pyridinium chloride: a new potent and selective inhibitor of bovine brain and human placental choline acetyltransferase.
A newly synthesized 1(2-benzoylethyl)pyridinium (BEP), an analog of the choline acetyltransferase (ChA) inhibitor (2-benzoylethyl)trimethylammonium (BETA), was evaluated for its ability to inhibit ChA from bovine brain and human placenta. Its ChA inhibitory properties were compared with that of BETA. BEP was found to be an effective inhibitor of ChA (I50: 10-18 microM). BEP, as well as BETA, was a linear noncompetitive inhibitor of ChA with respect to both substrates, acetylcoenzyme A and choline. BEP and BETA were poor inhibitors of electric eel acetylcholinesterase. These observations indicate that BEP is a potent and selective inhibitor of ChA. Furthermore, because of the possible delocalization of the positive charge at the N atom of the BEP molecule throughout the pyridine ring, it is anticipated that BEP would have a higher potential for lipid solubility, stability and selectivity than BETA.
Choudhuri
M S
MS
Department of Pharmaceutical Sciences/Toxicology, North Dakota State University College of Pharmacy, Fargo 58105.
Chaturvedi
A K
AK
D000109:Acetylcholine / Q000031:analogs & derivatives / Q000494:pharmacology; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002417:Cattle; D002795:Choline O-Acetyltransferase / Q000037:antagonists & inhibitors*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000302:isolation & purification; D007700:Kinetics; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D011726:Pyridinium Compounds / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D007527:Isoenzymes; D011726:Pyridinium Compounds; C017058:(2-benzoylethyl)trimethylammonium; C071431:1-(2-benzoylethyl)pyridinium; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D000109:Acetylcholine