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Blockade on sodium, potassium, and calcium channels by a new antiarrhythmic agent CPU 86017
Author(s) -
Dai DeZai,
Yu Feng,
Li HaiTao,
Tang Yiqun,
An LuFan,
Huang WenLong,
Peng SiXun,
Hao XueMei,
Zhou BeiAi,
Hu ChaiHong
Publication year - 1996
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/(sici)1098-2299(199610)39:2<138::aid-ddr5>3.0.co;2-q
Subject(s) - chemistry , ventricle , electrophysiology , depolarization , quinidine , antiarrhythmic agent , anti arrhythmia agents , sodium channel , inward rectifier potassium ion channel , pharmacology , propafenone , medicine , sodium , ion channel , receptor , biochemistry , heart disease , organic chemistry , atrial fibrillation
CPU 86017 is derived from tetrahydroberberine and possesses potent anti‐arrhythmic activities in animal models. Its effects on ion channels were studied by electrophysiological approaches. The action potential duration (APD) of isolated myocytes of guinea‐pigs and the mono‐phasic action potential duration (MAPD) of intact rabbit hearts were prolonged. CPU 86017 blocked the delayed outward rectifier current [I K ] by 30 ± 4% and the I K tail by 16 to 59% at 3–30 μM; no effect was shown on I K1 . V max of the isolated papillary muscle of guinea pigs was suppressed in a dose‐dependent manner by 4 to 48% at 0.3 to 30 μM CPU 86017. This effect on V max was reproduced under pathological conditions: anoxia and two hypertrophic ventricle models. The rate‐dependent block (RDB) of V max at steady state was 22% for CPU 86017, 30% for quinidine, and 50% for propafenone at 10 μM stimulated at 3 Hz. The maximal rate of depolarization of sinus pacing cells was markedly reduced by 48–70% at 3–30 μM. CPU 86017 is probably a complex Class III antiarrhythmic agent combined with Class I and Class IV properties. Drug Dev. Res. 39:138–146. © 1997 Wiley‐Liss, Inc.