Multi-target drugs are the most commonly prescribed drugs to treat atrial fibrillation, a heart condition resulting in irregular and rapid heart rate.

The researchers found that the multi-target drugs, which are the most commonly prescribed drugs to treat AF and are considered the most efficacious, may work by changing properties of the cell membrane, like elasticity, curvature and thickness.
“Generating and propagating the electrical impulse that controls heartbeat requires a delicate balance in activities of multiple membrane-embedded proteins. The multiple signaling pathways involved in heartbeat could explain why multi-target drugs could be particularly beneficial in treating conditions such as AF and why the cell membrane may play a key role in their regulation,” said Radda Rusinova, a researcher in the Department of Physiology and Biophysics at Weill Cornell Medical College in New York.
Amiodarone, one of the multi-target drugs that Rusinova and her colleagues tested, was initially classified as an antiarrhythmic that prolongs repolarization, which is a "resetting" of the electrical potential across a cell membrane before it can transmit another electrical signal. But other modes of action for the drug were quickly discovered, Rusinova said, and it is now known that amiodarone alters the function of numerous membrane proteins, with no clear mechanism for how it does so.
Rusinova and her colleagues found evidence that a previously unknown membrane-mediated mechanism may be involved in the way the drug changes function of cell membrane-embedded proteins. The researchers used a simplified lipid bilayer with a class of proteins called gramicidin channels embedded in it as a model cell membrane. The gramicidins act as a sort of spy for the researchers. By observing the activity of the gramicidins, the researchers can uncover information about the state of the bilayer.
By using the gramicidin "spies," Rusinova and her colleagues found that amiodarone, along with another multi-target antiarrhythmic drug called dronedarone, increase the elasticity of the bilayer. The elasticity of the bilayer, in turn, affects the function of the proteins embedded within it, similar to the way a changing sea affects all the boats that float on it.
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"The key conclusion of this work is that the contribution of bilayer effects on a drug's therapeutic profile is not trivial and has to be carefully examined," Rusinova said.
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Source-Eurekalert