Researchers identify universal bitter blocker that could help patients take their life-saving medications as prescribed

Many people, especially children and the elderly, have difficulty swallowing tablets. Liquid forms of many medications taste extremely bitter and are often rejected. Simply put, strong bitterness is the main reason why people around the world, especially children, avoid taking their medicines, thereby putting their health and sometimes their lives at risk.

Today, a group of scientists from the Monell Chemical Senses Center has identified the first temporary, universal taste blocker that works in humans. Their conclusions appear in the British Journal of Pharmacology.

“Remarkably, and unlike our experience with bitter taste receptor blockers, the taste nerve blocker we tested worked for every subject and every bitter compound we tested,” said first author Linda J. Flammer. , Ph.D., senior research associate at Monell. and Director of the Corporate Partner Program. “I had never seen that before.”

Until now, efforts to block bitterness in foods and medications have focused on finding blockers of bitter taste receptors on the tongue. Because different drugs activate distinct sets of bitter taste receptors, targeting specific receptors can only suppress bitterness for some, but not all, bitter-tasting compounds.

“There is a clear need to develop bitterness blockers that can suppress the bitterness of many medications,” said co-author Carol Christensen, Ph.D., a Monell faculty member. “Although humans have 25 different bitter receptors, our ongoing research suggests that only a handful of bitter receptors may be responsible for most of the bitterness in medications.”

Taste cells in the mouth that express the TAS2R family of taste receptors are stimulated by sweet, bitter, and salty compounds and transmit signals to nerve fibers by releasing adenosine triphosphate (ATP), the primary energy source of a cell. In turn, ATP activates a receptor called P2X2/P2X3 on the receiving nerve cells. These nerves send information to the brain about the taste of food and medicine.

The team used a P2X2/P2X3 receptor inhibitor, called AF-353, to block taste-nerve transmission and reduce the bitterness signal caused by drugs and other taste compounds. Several P2X2/P2X3 receptor blockers have been identified, some of which have been tested in clinical trials to treat chronic cough; however, a side effect in these trials was taste disturbance. The Monell team capitalized on the “side effects” of these compounds to create an oral treatment that improves the palatability of the drugs.

One of the main findings of the study is that rinsing your mouth with AF-353 significantly reduces the bitterness of two important drugs that treat common chronic diseases: praziquantel for parasites and tenofovir alafenamide (TAF) for hepatitis B and HIV.

“AF-353 is the first universal bitter taste blocker that has been identified,” said Monell faculty member Peihua Jiang, Ph.D. “In addition to bitter taste, it also affects salty, salty, sweet and sour tastes. , AF-353 only blocks taste. Other oral sensations such as tingling due to carbonation were not affected.

The team conducted both human sensory taste tests and mouse behavioral experiments to determine the magnitude, strength, and duration of the blocking effects. The results of human and rodent studies were similar in terms of the extent and duration of action of AF-353.

Topical application of AF-353 directly to the mouth can improve compliance with many important medications, especially those that save the lives of children in developing countries. “In humans, the blocking effect lasted 60 to 90 minutes, when their taste returned to normal,” Flammer said.

“We are now looking for taste blockers that act more quickly and allow the taste to return to normal sooner,” Jiang said.

Along with Flammer, Jiang, and Christensen, co-authors are Hillary Ellis, Natasha Rivers, Lauren Caronia, Misgana Y. Ghidewon, Paul AS Breslin, and Michael G. Tordoff, all of Monell. Breslin is also a faculty member at Rutgers University. Ghidewon is a student at the University of Pennsylvania.