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 dosage 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 lead 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/adherence 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.

Taste-Masking Effect of Chlorogenic Acid (CGA) on Bitter Drugs Evaluated by Taste Sensor and Surface Plasmon Resonance on the Basis of CGA–Drug Interactions

“…1) This may be important, especially for children, as it often causes poor compliance and consequently reduced drug efficacy. Therefore, taste masking may be necessary in order to inhibit the bitterness of some medicines.…”

Bitter tastant responses in the amoeba Dictyostelium correlate with rat and human taste assays

“…In addition to suggesting a potential new non-animal model for provisional bitter tastant screening, our data provides an interesting insight into this field from an evolutionary perspective, since rat bitter taste perception is considered an evolutionary conserved mechanism used to avoid toxic food chemicals (Meyerhof, 2005;Mennella et al, 2013). The ability to recognize and/or respond to bitter tastants is shared amongst phylogenetically diverse groups, including mammals (Stern et al, 2011), amphibians (Go, 2006;Mashiyama et al, 2014), fishes (Ishimaru et al, 2005), cephalopods (Darmaillacq et al, 2004), decapod crustacea (Aggio et al, 2012), insects and nematodes (Hilliard et al, 2004;Gordesky-Gold et al, 2008;Apostolopoulou et al, 2014).…”

Influences of weight, age, gender, genetics, diseases, and ethnicity on bitterness perception: a narrative review of current methodological aspects

“…The expression of the T2R bitter taste receptor occurs at oral sites, on the whole epithelium of the gastrointestinal system, as well as in the lungs, pancreas and brain [6,7]. Studies about genetics, genetic expression and sensory skills would help to understand these questions [8].…”