Universal bitter blocker could aid in medication adherence

A significant obstacle to effective medication consumption, particularly for children and elderly individuals, is the strong bitterness of many medicines. This aversion can lead to severe health risks and even death when patients refuse essential treatments. However, scientists at the Monell Chemical Senses Center have made a groundbreaking discovery: the first universal, temporary taste blocker that effectively works in humans.

The research, published in the British Journal of Pharmacology, reveals that this new taste blocker, identified as an inhibitor of P2X2/P2X3 receptors called AF-353, can suppress the bitterness of various compounds. This discovery marks a departure from previous methods that focused on blocking specific bitter taste receptors on the tongue, which proved to be ineffective for a wide range of bitter substances. According to lead researcher Linda J. Flammer, PhD, the newly identified taste-nerve blocker worked universally across all subjects and bitter compounds tested.

Efforts to mitigate bitterness in foods and medicines have historically been limited due to the complexity and diversity of bitter taste receptors in humans. While humans possess 25 different bitter receptors, only a few are responsible for the bitterness of most medicines. This complexity required a more holistic solution, which researchers at Monell have now provided.

Taste cells in the mouth utilize the TAS2R family of receptors to detect sweet, bitter, and savory compounds. These cells release adenosine triphosphate (ATP), which activates P2X2/P2X3 receptors on nerve cells, sending taste information to the brain. By using AF-353 to inhibit these specific receptors, the scientists effectively blocked the transmission of bitterness signals, thereby enhancing the palatability of medicines.

Interestingly, several P2X2/P2X3 receptor blockers had already been identified for treating chronic cough, albeit with the unintended side effect of taste disturbance. The Monell team leveraged this "side effect" to formulate AF-353 as an oral treatment to improve medicine palatability. This compound significantly reduced the bitterness of critical medicines like Praziquantel, used for parasites, and Tenofovir Alafenamide (TAF), used for hepatitis B and HIV.

Monell Faculty Member Peihua Jiang, PhD, stated that AF-353 is the first universal bitter taste blocker identified to date. Besides its impact on bitterness, AF-353 also affects savory, salt, sweet, and sour tastes, although it does not interfere with other oral sensations, such as the tingle from carbonation. The efficacy of AF-353 was confirmed through both human sensory taste testing and mouse behavioral experiments, showing consistent results in terms of breadth and duration of its blocking effects.

The practical application of AF-353 holds promise for improving adherence to essential medications, particularly in children from developing countries where palatable medication could save countless lives. According to Linda J. Flammer, the blocking effect of AF-353 lasted between 60 to 90 minutes, after which normal taste sensation was restored.

The team is now focusing on developing faster-acting taste blockers that allow taste sensations to return to normal more quickly. This ongoing research aims to refine and enhance the potential of taste blockers, ensuring they are both effective and convenient for patients worldwide.