Sniffing out pharmacology: interactions of drugs with human olfaction

Advances in the understanding of the sense of smell have increased awareness of the role of olfaction in human life. Odors are perceived via specific G protein-coupled receptors (GPCRs) with cAMP as the second messenger. Drugs that interact with this signaling cascade, such as opioids, cannabinoids and sildenafil, are known to reduce olfactory function. Drugs that are active in the central nervous system (CNS) may also hinder the complex processing of olfactory information to distinguish, via pattern recognition, thousands of odors from the signals of only ∼400 distinct olfactory receptors. Many other interactions with drug targets expressed at the olfactory bulb are also likely to occur. However, olfactory drug effects have rarely been explored in controlled studies. In the current activities of drug development and re-purposing, olfaction could become highly important because it can impact significantly upon the enjoyment of food. With an established molecular basis and using available tools, the assessment of olfaction in drug development and approval is advised.