Interactions of N, N‐ diethyl‐ meta ‐toluamide (DEET) and Novel Insect Repellents with Mammalian GABA A and Glycine Receptors

Mosquito‐borne diseases such as malaria, dengue and yellow fever are responsible for millions of deaths annually. Repellents disrupt interactions between humans and insects, thus providing personal protection from bites through which diseases are transmitted. The most commonly used repellent today is N, N‐ diethyl‐ meta ‐toluamide, DEET. Despite its popularity, DEET is not effective against all species of mosquitoes, and there are widespread concerns about its possible toxicity to users. Consequently, there is a demand for new repellents which are safer, effective for longer durations, and more efficacious against a broader range of arthropods. The novel repellents tested in the following study fall under two classes of chemicals: acylpiperidines and carboxamides. In the present electrophysiological investigation, the neurotoxicity of these novel repellents was explored relative to that of DEET, focusing on the effects of the repellents on inhibitory neurotransmitter receptors. Two‐electrode voltage clamp technique was employed with Xenopus laevis oocytes expressing mammalian GABA A (α 1 β 3 γ 2S ) and glycine (α 1 homomer) receptors. Results indicated that high concentrations of DEET negatively modulated glycine receptor activity when co‐applied with submaximal glycine concentrations. 1 mM DEET inhibited glycine receptor activity by 48.4% ± 4.0% and 10 mM DEET produced a maximal inhibition of 80.4% ± 3.2%. Interestingly, most carboxamides (including DEET) inhibited the activity of glycine receptors, while the acylpiperidines enhanced the activity of glycine receptors, acting as positive modulators. Neither acylpiperidines nor carboxamides were found to inhibit the activity of GABA A receptors, with DEET and other carboxamides acting as weak agonists at high concentrations (>1 mM) to produce directly‐activated GABA currents. The EC 50 for the activation of GABA A receptors by DEET was 4760.4 ± 50.6 μM, compared to a GABA EC 50 of 42.9 ± 8.0 μM. These data suggest that DEET and the novel repellents have distinct effects on mammalian GABA A and glycine receptors. Furthermore, the results highlighted a stark difference between the two classes of chemicals, whereby acylpiperidines have the potential to result in less neurotoxicity relative to carboxamides. Like strychnine, carboxamides, including DEET, act as competitive antagonists at glycine receptors albeit with considerably less potency. Support or Funding Information Blakeslee and Holmes funding, Smith College This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .