Scientists develop an improved pharmaceutical drug for the treatment of atrial fibrillation

Scientists from the Department of Pharmacy at the National University of Singapore (NUS) have developed an improved pharmaceutical drug for the treatment of the most common heart rhythm disturbance – atrial fibrillation (AF). The 8-member research team took 8 years to achieve this technological breakthrough that could benefit millions of AF patients worldwide.

AF is a serious disease that can lead to heart failure, early death and stroke. For patients with AF, there are currently medications that are used to control AF and maintain a normal rhythm. Ironically, these drugs, while treating AF, can promote another type of heart rhythm disturbance in the lower chambers of the heart, also called ventricular arrhythmia, which is potentially more dangerous or even fatal. Some of these existing AF drugs are also toxic to other organs such as the liver, lungs, and thyroid gland. Therefore, there is an unmet need to develop effective and safer drugs to treat AF.

Patents have been filed for the new drug candidate, called poyendarone. The research team tested poyendarone in laboratory studies and the promising results position the drug as a game changer with greater safety and efficacy for clinical trials. It should be noted that there has been no AF drug approved by regulatory authorities since 2009.

The results were first published in the journal Acta Pharmaceutica Sinica B on March 16, 2022.

New effective drug with reduced side effects

The research team led by Professor Eric Chan from the Department of Pharmacy at NUS has found that a current AF drug called dronedarone inactivates a key enzyme in the heart. Normally, the enzyme converts an unsaturated fatty acid into metabolites that facilitate cardiac physiological functions such as normal beats and heart muscle cell well-being. Dronedarone is metabolized by the cardiac enzyme to form a drug metabolite which can irreversibly bind to the active site of the enzyme, thereby inactivating it. Inactivation of the enzyme in turn causes ventricular arrhythmia. Patients who experience ventricular arrhythmia due to dronedarone should discontinue the drug immediately while other treatment options are considered.

Armed with this knowledge, the NUS team succeeded in circumventing this potentially fatal side effect by modifying the chemical structure of dronedarone. This was done by the subtle replacement of selected hydrogen atoms present on the drug molecule with deuterium atoms, in a process known as deuteration. Thanks to this change, the reactivity of the metabolite is reduced and it is no longer able to inactivate the key enzyme of the heart. Through laboratory studies, the team also discovered that the improved drug retains several favorable properties related to the drug, such as how effectively it treats AF and can be effectively treated by the body. Like dronedarone, the new drug molecule poyendarone is expected to be administered in tablet form.

Developing an improved version of an existing drug that is both effective and safer is important to address the unmet medical need in the treatment of AF. Professor Chan said: “This is the first time that a drug discovery strategy has been applied to maximize efficacy while mitigating side effects of a drug molecule. Our research results demonstrate an innovative discovery platform that can improve patient care through the development of effective drugs and safe pharmaceuticals.”

There is a strong need to develop safe, effective and accessible anti-arrhythmic treatments to manage the ever-increasing number of AF patients worldwide, which is currently estimated at over 35 million. Poyendarone represents a paradigm shift in improving the characteristics of current drugs, selectively eliminating dangerous side effects and organ toxicities while maintaining its ability to regulate abnormal heart rhythm.”

Dr. Pipin Kojodjojo, Clinical Fellow, Cardiologist at Asian Heart & Vascular Center (AHVC) Singapore and Adjunct Associate Professor at NUS Yong Loo Lin School of Medicine

Drug development plans

The research team is exploring opportunities to conduct relevant clinical trials that will establish the safety and efficacy of the drugs, enabling regulatory approval and commercial availability.


national university of singapore

Journal reference:

Karkhanis, AV, et al. (2022) Site-directed deuteration of dronedarone preserves cytochrome P4502J2 activity and attenuates its cardiac adverse effects in canine arrhythmic hearts. Acta Pharmaceutica Sinica B.

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