Optimizing Odorants for Olfactory Training Based on Olfactory Receptor-Ligand Pair Analysis

To optimize olfactory training (OT) by identifying a scientifically grounded combination of odorants that maximally stimulate human olfactory receptors (ORs) through the utilization of a comprehensive receptor-ligand interaction dataset.

We analyzed 75,050 OR-odor pair experiments from the M2OR database, focusing on 385 unique human ORs and 510 unique odorants. Utilizing human olfactory epithelium transcriptomic data, we identified highly abundant ORs and evaluated their interactions with various odorants to determine the optimal odorant combination for maximizing OR stimulation. The effectiveness of the classical OT odorants (rose, lemon, eucalyptus, and clove) in maximal OR stimulation was also evaluated and compared to the optimal odor combination.

A novel four-odorant combination (galaxolide, eugenol acetate, [-]-menthol, and geranyl acetate) would stimulate 323 ORs (83.9% of 385 ORs), covering 69.9% of estimated OR expression. In comparison, the classical four OT odor mixture would stimulate 151 ORs (39.2% of 385 ORs), covering 32.9% of estimated OR expression. Both odorant combinations stimulated a large proportion of highly abundant ORs, presumed to be functionally important. These findings suggest that while the classical odors have a substantial effect, the novel odorant combination has the potential to offer significantly broader receptor activation and improved outcomes in OT.

This receptor-based approach provides a scientifically grounded method for optimizing OT. Further clinical validation is necessary to confirm the therapeutic efficacy of this approach.