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Electrophysiological Properties of HBI-3000: A New Antiarrhythmic Agent With Multiple-channel Blocking Properties in Human Ventricular Myocytes

Guo, Donglin MD, PhD*; Liu, Que MD, PhD†; Liu, Tengxian BS*; Elliott, Gary PharmD, PhD†; Gingras, Mireille PhD†; Kowey, Peter R*‡; Yan, Gan-Xin MD, PhD*‡

Journal of Cardiovascular Pharmacology: January 2011 - Volume 57 - Issue 1 - pp 79-85
doi: 10.1097/FJC.0b013e3181ffe8b3
Original Article

HBI-3000 (sulcardine sulfate) has been shown to suppress various ventricular arrhythmias in animal models. The electrophysiological properties of HBI-3000 were investigated using standard microelectrode and patch-clamp techniques in single human ventricular myocytes. HBI-3000 led to concentration-dependent suppression of dofetilide-induced early afterdepolarizations in single nonfailing human ventricular myocytes and early afterdepolarizations seen in failing ventricular myocytes. The concentration-dependent prolongation of action potential duration (APD) by HBI-3000 was bell shaped with maximum response occurring around 10 μM. Interestingly, HBI-3000 at the concentration of 10 μM modestly prolonged the APD at all 3 basic cycle lengths. The slope of APD-cycle length curve of HBI-3000 was only slightly steeper than that of control (88.8 ± 7.7 ms/s vs. 78.9 ± 5.2 ms/s in control, n = 8, P > 0.05). HBI-3000 only showed a minimal use-dependent prolongation of the APD in human ventricular myocytes. HBI-3000 inhibited fast sodium current (INa-F), late sodium channel (INa-L), L-type calcium current (ICa-L), and rapidly activating delayed rectifier K+ current (IKr) in single human ventricular myocytes. The estimated half-maximal inhibitory concentration values of INa-F, INa-L, ICa-L, and IKr were 48.3 ± 3.8, 16.5 ± 1.4, 32.2 ± 2.9, and 22.7 ± 2.5 μM, respectively. The ion channel profile and electrophysiological properties of HBI-3000 are similar to those of ranolazine and chronic amiodarone (reduced INa-F, INa-L, ICa-L, and IKr). HBI-3000 may be a promising antiarrhythmic agent with low proarrhythmic risk.

From the *Lankenau Institute for Medical Research & Main Line Health Heart Center, Wynnewood, PA; †HUYA Bioscience International, San Diego, CA; and ‡Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA.

Received for publication May 11, 2010; accepted October 1, 2010.

Supported by an unrestricted grant from HUYA Bioscience International.

Dr Que Liu is a former employee of HUYA Bioscience International. Drs Gary Elliott and Mireille Gingras are employees of HUYA Bioscience International. Dr Peter Kowey has been a consultant for HUYA Bioscience International on matters unrelated to the subject of this article and received no remuneration from the proceeds of this grant.

D. Guo and Q. Liu contributed equally to this work.

The author report no conflict of interest.

Reprints: Donglin Guo, MD, PhD, Lankenau Institute for Medical Research & Main Line Health Heart Center, 100 Lancaster Avenue, Wynnewood, PA 19096 (e-mail: or

© 2011 Lippincott Williams & Wilkins, Inc.