(2-Benzoylethyl)trimethylammonium chloride: a new, selective and stable inhibitor of human placental choline acetyl transferase.

(2-Benzoylethyl)trimethylammonium chloride (BETA), a keto analog of acetylcholine, was synthesized and studied as an inhibitor of human placental choline acetyltransferase (ChA). It is a potent inhibitor of ChA with an 150 of 3.1 X 10(-6) M. The inhibition was rapid in onset and was slowly reversible. Upon dialysis of the inhibited ChA, 50% activity was recovered within about 4.90 hours. BETA was noncompetitive with respect to both substrates of ChA, acetyl-CoA and choline. BETA was selective for inhibiting ChA. It was about 100, and 50, times more potent for inhibiting ChA than acetylcholinesterase, and cholinesterase, respectively. Its activities at muscarinic and nicotinic receptors were negligible at the concentrations where complete inhibition of ChA was obtained. In contrast to the other ChA inhibitors, the styrylpyridines and halogenoacetylcholines, BETA is stable in solution. On prolonged storage (several days at 37 degrees C and pH 7.4), solutions of BETA decomposed partially into trimethylamine and vinylphenylketone. Beta was considerably more stable and more selective than other inhibitors of ChA.