Harnessing Odorant Receptor Activation to Suppress Real Malodor.

Mammals, including humans, sense smell by the responses of odorant receptors (ORs) to odor molecules. We have developed an effective method to identify novel antagonists capable of suppressing the pungent odor of cat urine by targeting specific ORs. Since odors are typically complex mixtures of multiple volatile compounds, olfactory perception can vary depending on the composition. We analyzed the response of ORs to cat urine odor using vapor stimulation assays to identify the responding ORs. Gas chromatography-mass spectrometry was then performed to identify compounds eliciting responses from these ORs. Trace-amine-associated receptor 5 (TAAR5) demonstrated a significant response associated with the odor intensity of cat urine, identifying trimethylamine as a major contributor to the strong odor. From hundreds of candidate compounds, we identified several novel antagonists that exhibited greater efficacy than a known TAAR5 antagonist. These compounds not only reduced the responses of TAAR5-expressing cells to cat urine odor but also significantly reduced odor intensity and improved sensory pleasantness in human tests. Our findings suggest that targeting ORs responsive to specific odors, without isolating their individual components, is a promising strategy for developing deodorizing agents against complex malodors like cat urine odor. This study emphasizes the value of using real odor mixtures to enhance our understanding of odor perception.