Original ArticleMechanisms of Cardiac Muscle Insensitivity to a Novel Acetylcholinesterase Inhibitor C-547Abramochkin, Denis V PhD*†; Petrov, Konstantin A PhD‡; Zobov, Vladimir V PhD‡; Yagodina, Lilia O PhD§; Nikolsky, Eugen E MD§; Rosenshtraukh, Leonid V PhD*Author Information From the *Institute of Experimental Cardiology, Laboratory of Heart Electrophysiology, Moscow, Russia; †Department of Human and Animal Physiology, Moscow State University, Moscow, Russia; ‡Institute of Organic and Physical Chemistry, Laboratory of Chemical and Biological Researches, Russian Academy of Sciences, Kazan, Russia; and §Kazan Institute of Biochemistry and Biophysics, Laboratory of Biophysics of Synaptic Processes, Russian Academy of Sciences, Kazan, Russia. Received for publication may 23, 2008; accepted December 10, 2008. Supported by the Russian Foundation for Basic Research (RFBR) 07-04-01137 for E.E.N., K.A.P., and V.V.Z.; RFBR 07-04-12097 for E.E.N., K.A.P., and V.V.Z.; and grant of President RF Scientific School 41. There are no conflict of interests. Reprints: Denis V. Abramochkin, PhD, Department of Human and Animal Physiology, Biological Faculty, Moscow State University, Leninskie Gory, 1, 12, Moscow 19992, Russia (e-mail: [email protected]). Journal of Cardiovascular Pharmacology: February 2009 - Volume 53 - Issue 2 - p 162-166 doi: 10.1097/FJC.0b013e31819867d1 Buy Metrics Abstract We compared the effects of the novel acetylcholinesterase (AChE) inhibitor C-547 on action potential configuration and sinus rhythm in the isolated right atrium preparation of rat with those of armin and neostigmine. Both armin (10−7, 10−6, and 10−5 M) and neostigmine (10−7, 10−6, and 5 × 10−6 M) produced a marked decrease in action potential duration and slowing of sinus rate. These effects were abolished by atropine and are attributable to the accumulation of acetylcholine in the myocardium. The novel selective AChE inhibitor C-547 (10−9 to 10−7 M), an alkylammonium derivative of 6-methyluracil, had no such effects. The inhibition constant of C-547 on cardiac AChE is 40-fold higher than that on extensor digitorum longus muscle AChE. These results suggest that C-547 might be employed to treat diseases such as myasthenia gravis or Alzheimer disease, without having unwanted effects on the heart. © 2009 Lippincott Williams & Wilkins, Inc.