The bad taste of medicines: overview of basic research on bitter taste

Abstract

Background: Many active pharmaceutical ingredients taste bitter and thus are aversive to children as well as many adults. Encapsulation of the medicine in pill or tablet form, an effective method for adults to avoid the unpleasant taste, is problematic for children. Many children cannot or will not swallow solid dose forms.

Objective: This review highlights basic principles of gustatory function, with a special focus on the science of bitter taste, derived from studies of animal models and human psychophysics. We focus on the set of genes that encode the proteins that function as bitter receptors as well as the cascade of events that leads to multidimensional aspects of taste function, highlighting the role that animal models played in these discoveries. We also summarize psychophysical approaches to studying bitter taste in adult and pediatric populations, highlighting evidence of the similarities and differences in bitter taste perception and acceptance between adults and children and drawing on useful strategies from animal models.

Results: Medicine often tastes bitter, and because children are more bitter-sensitive than are adults, this creates problems with compliance. Bitter arises from stimulating receptors in taste receptor cells, with signals processed in the taste bud and relayed to the brain. However, there are many gaps in our understanding of how best to measure bitterness and how to ameliorate it, including whether it is more efficiently addressed at the level of receptor and sensory signaling, at the level of central processing, or by masking techniques. All methods of measuring responsiveness to bitter ligands-in animal models through human psychophysics or with "electronic tongues"-have limitations.

Conclusions: Better-tasting medications may enhance pediatric adherence to drug therapy. Sugars, acids, salt, and other substances reduce perceived bitterness of several pharmaceuticals, and although pleasant flavorings may help children consume some medicines, they often are not effective in suppressing bitter tastes. Further development of psychophysical tools for children will help us better understand their sensory worlds. Multiple testing strategies will help us refine methods to assess acceptance and compliance by various pediatric populations. Research involving animal models, in which the gustatory system can be more invasively manipulated, can elucidate mechanisms, ultimately providing potential targets. These approaches, combined with new technologies and guided by findings from clinical studies, will potentially lead to effective ways to enhance drug acceptance and compliance in pediatric populations.

Keywords: animal models; bitter taste; children; drug compliance; electronic tongues; psychophysics.

© 2013 Elsevier HS Journals, Inc. All rights reserved.

Figures

Figure

How Bitter Works: the process of bitter perception. The generation of bitter taste starts when a bitter compound enters the oral cavity, where the ligand binds to a T2R G-protein coupled receptor expressed in the apical membrane of receptor cells found in taste buds, triggering a cascade of signaling events, leading to the release of neurotransmitter that activates an afferent nerve fiber that transmits the signal via the cranial nerve to the brain. Taste buds are distributed in distinct fields in the oral, pharyngeal, and laryngeal epithelia, with each field innervated by a different cranial nerve branch. Only the taste buds on the tongue are depicted in the figure. The taste buds of the laryngeal epithelium are thought to be involved more with protection of the airways. Taste receptors have also been identified in a variety of nongustatory tissues, such as the gut, where they have been proposed to play a role in nutrient and toxin sensing. The taste signals course through the brain and provide input to circuits that subserve various functions, such as oromotor and physiological reflexes, discriminative perception, and affective processing. The figure illustrates the complexity of the mechanisms intervening between the application of the bitter stimulus and the generation of the behavioral response, providing a variety of potential targets for strategies to modulate the bitterness of medications. VPMPC, ventral posterior medial nucleus, parvocellular subdivision. *The insula/operculum is actually lateral to the sagittal plane of section shown. Cell and molecular segment adapted from Finger and Kinnamon (2011).