Skip Navigation LinksHome > January 2011 - Volume 57 - Issue 1 > Electrophysiological Properties of HBI-3000: A New Antiarrhy...
Journal of Cardiovascular Pharmacology:
doi: 10.1097/FJC.0b013e3181ffe8b3
Original Article

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*‡

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Abstract

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.

© 2011 Lippincott Williams & Wilkins, Inc.

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