Abramochkin Denis V, Petrov Konstantin A, Zobov Vladimir V, Yagodina Lilia O, Nikolsky Eugen E, Rosenshtraukh Leonid V
Institute of Experimental Cardiology, Laboratory of Heart Electrophysiology, Moscow, Russia.
J Cardiovasc Pharmacol. 2009 Feb;53(2):162-6. doi: 10.1097/FJC.0b013e31819867d1.
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 x 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.
我们比较了新型乙酰胆碱酯酶（AChE）抑制剂C-547与阿米三嗪和新斯的明对大鼠离体右心房标本动作电位形态和窦性心律的影响。阿米三嗪（10⁻⁷、10⁻⁶和10⁻⁵ M）和新斯的明（10⁻⁷、10⁻⁶和5×10⁻⁶ M）均使动作电位时程显著缩短，窦性心率减慢。这些效应可被阿托品消除，且归因于心肌中乙酰胆碱的蓄积。新型选择性AChE抑制剂C-547（10⁻⁹至10⁻⁷ M），一种6-甲基尿嘧啶的烷基铵衍生物，无上述效应。C-547对心脏AChE的抑制常数比对趾长伸肌AChE的抑制常数高40倍。这些结果表明，C-547可用于治疗重症肌无力或阿尔茨海默病等疾病，而对心脏无不良影响。
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