Insect Odorant Receptors Are Molecular Targets of the Insect Repellent DEET

Mathias Ditzen, Maurizio Pellegrino, Leslie B. Vosshall^*

Abstract: DEET (N,N-diethyl-meta-toluamide) is the world's most widely used topical insect repellent, with broad effectiveness against most insects. Its mechanism of action and molecular target remain unknown. Here, we show that DEET blocks electrophysiological responses of olfactory sensory neurons to attractive odors in Anopheles gambiae and Drosophila melanogaster. DEET inhibits behavioral attraction to food odors in Drosophila, and this inhibition requires the highly conserved olfactory co-receptor OR83b. DEET inhibits odor-evoked currents mediated by the insect odorant receptor complex, comprising a ligand-binding subunit and OR83b. We conclude that DEET masks host odor by inhibiting subsets of heteromeric insect odorant receptors that require the OR83b co-receptor. The identification of candidate molecular targets for the action of DEET may aid in the design of safer and more effective insect repellents.

Laboratory of Neurogenetics and Behavior, The Rockefeller University, 1230 York Avenue, Box 63, New York, NY 10065 USA.

^* To whom correspondence should be addressed. E-mail: leslie{at}mail.rockefeller.edu

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