HBI-3000

The molecular problem

Anti-arrhythmic medication is taken to treat irregular beating of the heart. This irregular beating results from a deregulation of the initiation or propagation of the electrical stimulus of the heart. The most common chronic arrhythmia is atrial fibrillation. There is an increased incidence of atrial fibrillation in the elderly and some examples of complications include heart failure exacerbation, hypotension, and thromboembolic events.

Most anti-arrhythmic medications exert their effects by decreasing the permeability of potassium ion channels (IKr) in heart cells. These potassium channel blockers delay ventricular repolarization and prolong action potential duration (APD; the prolongation of the electrical stimulus within heart cells). These changes can lower heart rate, eliminate atrial fibrillation, and ultimately sudden cardiac death.

Mechanism of action in ventricular myocytes

Ventricular myocytes are heart muscle cells found in the lower chambers of the heart. Heart rate is dependent on the movement of an electrical stimulus through the individual heart cells. This is mediated by the opening of ion channels on cell surfaces. HBI-3000 exerts its effects on the heart by inhibiting multiple ion channels (INa-F, INa-L, ICa-L and IKr), but predominantly the INa-L ion channel. By decreasing the ion permeability of these channels, HBI-3000 slightly prolongs APD (due to IKr); however, unlike pure IKr channel blockers, it is self-limited (due to the decreased permeability of INa-L and ICa-L). This is similar to the medications ranolazine and amiodarone. HBI-3000 suppresses early afterdepolarizations (EADs; a change in the normal net flow of ions during repolarization), does not produce any electrical abnormalities, and displays minimally pronounced prolongation of APD during a slow heart rate (i.e. stimulated at a slower frequency). Pronounced prolongation of APD during a slow heart rate can lead to proarrythmias. Overall, HBI-3000 seems to have a low proarrhythmic risk. The effect of HBI-3000 on contractility and cardiac conduction requires further investigation.

Studies

Animal model

In a canine model, the intravenous injection of HBI-3000 demonstrated to be an effective anti-arrhythmic and anti-fribrillatory agent.

Cellular isolation

The administration of HBI-3000 to isolated heart muscle cells demonstrated the potential to improve arrhythmias while having low proarrhythmic risk.

Human studies

Jiangsu Furui Pharmaceuticals Co., Ltd is currently recruiting participants in their study.

References

References

1. Jiangsu Furui Pharmaceuticals. (November 5, 2010). "Efficacy and safety of sulcardine sulfate tablets in patients with premature ventricular contractions". U.S. National Library of Medicine.
2. . ["HUYA Bioscience Int'l announces clinical trial milestones in China for promising new anti-arrhythmic compound; Data supports desirable safety profile"](https://www.huyabio.com/huya-bioscience-intl-announces-clinical-trial-milestones-china-promising-new-anti-arrhythmic-compound-data-supports-desirable-safety-profile/). *HUYA Bioscience International*.
3. (2011). "Atrial fibrillation: A primary care cross-sectional study". Israel Medical Association Journal.
4. (1998). "Comparison of the antiarrhythmic and the proarrhythmic effect of almokalant in anaesthetised rabbits". European Journal of Pharmacology.
5. (2011). "Electrophysiological properties of HBI-3000: A new antiarrhythmic agent with multiple-channel blocking properties in human ventricular myocytes". Journal of Cardiovascular Pharmacology.
6. (2010). "HBI-3000 prevents sudden cardiac death in a conscious canine model". Heart Rhythm.