The enigmatic reception of DEET - the gold standard of insect repellents.

Repellents are important prophylactic tools for travelers and populations living in endemic areas of malaria, dengue, encephalitis, and other vector-borne diseases. DEET is a safe, broad spectrum repellent, which provides complete protection over a long period of time. Despite its low cost, more affordable alternatives are highly desirable, particularly for those in endemic areas where cost is an impediment. Alternative compounds like IR 3535 and picaridin have been developed using molecular modeling, but the lack of knowledge of the molecular target(s) for DEET has retarded progress towards low cost alternatives. It is known that DEET acts at a distance as an odorant as well as by direct contact, i.e., as a tastant, although DEET reception is primarily mediated by the olfactory system. There is unambiguous evidence that olfactory receptor neurons are involved, and that an odorant receptor co-receptor Orco is essential for DEET reception. In the southern house mosquito, Culex quinquefasciatus, DEET triggers repellence by direct activation of an odorant receptor, CquiOR136, which is also sensitive to a plant defense compound, methyl jasmonate.