piperidines and terpin

Mosquito-borne disease is an annual problem in Australia, with endemic pathogens such as Ross River virus infecting thousands of people each year. The recent emergence of Zika virus in South America and the Pacific, together with ongoing outbreaks of dengue viruses in Southeast Asia, generated great community interest in the most effective strategies to avoid mosquito bites. Large-scale mosquito control programs are not common in Australia and are limited in New South Wales (NSW). The use of topical insect repellents is a key recommendation by health authorities to prevent mosquito-borne disease. All products sold in Australia purporting to repel mosquitoes must be registered with the Australian Pesticides and Veterinary Medicines Authority. Despite around 100 commercial products registered as repelling mosquitoes, there are relatively few active ingredients used across these formulations. The most common are diethyltoluamide (DEET), picaridin, p-menthane-3,8-diol (PMD) and a range of plant-derived products (e.g. melaleuca, eucalyptus, citronella oils). Research has shown that each of these active ingredients varies in the duration of protection provided against biting mosquitoes. Recommendations by health authorities are informed by this research, but inconsistencies between recommendations and available repellent formulations and their concentration of active ingredients can cause confusion in the community. There are conflicts between the data resulting from scholarly research, marketing promotion by manufacturers and recommendations provided by overseas health authorities. A review was undertaken of NSW Health's current recommendations on choosing and using insect repellents, taking into consideration recent research and currently registered topical repellents.

Topics: Animals; Australia; Culicidae; Cyclohexane Monoterpenes; DEET; Humans; Insect Repellents; Menthol; Piperidines; Practice Guidelines as Topic

In addition to its primary function as an insect repellent, DEET has many "off-label" properties, including a deterrent effect on the attraction of gravid female mosquitoes. DEET negatively affects oviposition sites. While deorphanizing odorant receptors (ORs) using the Xenopus oocyte recording system, we have previously observed that DEET generated outward (inhibitory) currents on ORs sensitive to oviposition attractants. Here, we systematically investigated these inhibitory currents. We recorded dose-dependent outward currents elicited by DEET and other repellents on ORs from Culex quinquefasciatus, Aedes aegypti, and Anopheles gambiae. Similar responses were observed with other plant-derived and plant-inspired compounds, including methyl jasmonate and methyl dihydrojasmolate. Inward (regular) currents elicited by skatole upon activation of CquiOR21 were modulated when this oviposition attractant was coapplied with a repellent. Compounds that generate outward currents in ORs sensitive to oviposition attractants elicited inward currents in a DEET-sensitive receptor, CquiOR136. The best ligand for this receptor, methyl dihydrojasmolate, showed repellency activity but was not as strong as DEET in our test protocol.

Topics: Aedes; Animals; Anopheles; Chemotaxis; Culex; Cyclohexane Monoterpenes; DEET; Insect Proteins; Insect Repellents; Menthol; Oviposition; Piperidines; Propionates; Receptors, Odorant

Topics: Animals; Attitude to Health; Consumer Health Information; Culicidae; Cyclohexane Monoterpenes; DEET; Eucalyptus; Health Behavior; Health Education; Humans; Insect Bites and Stings; Insect Repellents; Menthol; Mosquito Control; Phytotherapy; Piperidines; Plant Extracts; Time Factors

Topics: Animals; Culicidae; Cyclohexane Monoterpenes; DEET; Humans; Insect Bites and Stings; Insect Repellents; Malaria; Menthol; Piperidines; Travel

Topics: Animals; Bites and Stings; Culicidae; Cyclohexane Monoterpenes; Cymbopogon; DEET; Humans; Insect Repellents; Menthol; Piperidines; Propionates; Ticks

Insect repellents are important prophylactic tools for travelers and populations living in endemic areas of malaria, dengue, encephalitis, and other vector-borne diseases. DEET (N,N-diethyl-3-methylbenzamide) is a 6-decade-old synthetic repellent, which is still considered the gold standard of mosquito repellents. Mosquitoes use their sense of smell to detect DEET, but there are currently two hypotheses regarding its mode of action: activation of ionotropic receptor IR40a vs. odorant receptor(s). Here, we demonstrate that DEET, picaridin, insect repellent 3535, and p-menthan-3,8-diol activate the odorant receptor CquiOR136 of the southern house mosquito, Culex quinquefasciatus. Electrophysiological and behavioral assays showed that CquiIR40a knockdown had no significant effect on DEET detection and repellency. By contrast, reduction of CquiOR136 transcript levels led to a significant decrease in electroantennographic responses to DEET and a complete lack of repellency. Thus, direct activation of an odorant receptor, not an ionotropic receptor, is necessary for DEET reception and repellency in Culex mosquitoes. Interestingly, methyl jasmonate, a repellent derived from the nonvolatile jasmonic acid in the signaling pathway of plant defenses, elicited robust responses in CquiOR136•CquiOrco-expressing Xenopus oocytes, thus suggesting a possible link between natural products with long insect-plant evolutionary history and synthetic repellents.

Topics: Acetates; Aldehydes; Animals; Arthropod Antennae; Avoidance Learning; beta-Alanine; Cloning, Molecular; Culex; Cyclohexane Monoterpenes; Cyclopentanes; DEET; Electrophysiology; Feeding Behavior; Female; Insect Repellents; Menthol; Models, Neurological; Molecular Sequence Data; Oocytes; Oxylipins; Piperidines; Receptors, Ionotropic Glutamate; Receptors, Odorant; Recombinant Fusion Proteins; RNA Interference; Smell; Transcription, Genetic; Xenopus laevis

IR3535, KBR3023, para-Menthane-3,8-diol (PMD), and deet were evaluated in controlled studies with human subjects (n = 5) for repellency to black salt marsh mosquitoes (Ochlerotatus taeniorhynchus Wiedemann), in the Everglades National Park, FL. In tests of 6-h duration, with an average mosquito biting pressure on exposed forearm skin of 19.5 (+/- 13.7) bites per minute, the mean percent repellencies (SE) for IR3535, KBR3023, PDM, and deet was 88.6 (3.2), 97.5 (1.7), 89.2 (2.9), and 94.8 (2.5), respectively. Mean complete protection times (SE) for IR3535, KBR3023, PMD), mean deet were 3.0 (1.0), 5.4 (0.6), 3.8 (1.4), and 5.6 (0.5) h, respectively. Untreated (ethanol) controls provided 0% repellency. When mosquito biting rates on the untreated forearm skin of repellent-treated subjects were compared with biting rates on the forearm skin of control subjects, the former were 23%-40% lower early in tests and as much as 22% higher late in tests. These differences cast doubt on the technical merit of test designs comprising evaluation of more than one repellent at a time on the same human subject while underscoring the importance of untreated subjects as negative controls in field repellent bioassays.

Topics: Activity Cycles; Animals; Culicidae; Cyclohexane Monoterpenes; Florida; Humans; Insect Bites and Stings; Insect Repellents; Insecticides; Menthol; Piperidines; Propionates; Terpenes