Menthol acts as a positive allosteric modulator on nematode levamisole sensitive nicotinic acetylcholine receptors.

The ongoing and widespread emergence of resistance to the existing anti-nematodal pharmacopeia has made it imperative to develop new anthelminthic agents. Historically, plants have been important sources of therapeutic compounds and offer an alternative to synthetic drugs. Monoterpenoids are phytochemicals that have been shown to produce acute toxic effects in insects and nematodes. Previous studies have shown nicotinic acetylcholine receptors (nAChRs) to be possible targets for naturally occurring plant metabolites such as carvacrol and carveol. In this study we examined the effects of monoterpenoid compounds on a levamisole sensitive nAChR from Oesophagostomum dentatum and a nicotine sensitive nAChR from Ascaris suum. We expressed the receptors in Xenopus laevis oocytes and used two-electrode voltage-clamp to characterize the effect of various compounds on these cys-loop receptors. At 100 µM the majority of these compounds acted as antagonists. Interestingly, further experiments revealed that both 0.1 µM and 10 µM menthol potentiated acetylcholine and levamisole responses in the levamisole sensitive receptor but not the nicotine sensitive receptor. We also investigated the effects of 0.1 µM menthol on the contractility of A. suum somatic muscle strips. Menthol produced significant potentiation of peak contractions at each concentration of acetylcholine. The positive allosteric modulatory effects of menthol in both in vivo and in vitro experiments suggests menthol as a promising candidate for combination therapy with cholinergic anthelmintics.

Dissipation of double-stranded RNA in aquatic microcosms.

Silencing genes of a pest with double-stranded RNA (dsRNA) is a promising new pest management technology. As part of the environmental risk assessment for dsRNA-based products, the environmental fate and the potential for adverse effects to on-target organisms should be characterized. In the present study, a nonbioactive dsRNA was spiked into the water column of a water and sediment microcosm to mimic drift from a spray application run off of unbound dsRNA or transport of plant tissues. Dissipation of dsRNA in the water column and partitioning into sediment was determined. The dsRNA rapidly dissipated in the water column and was below the limit of detection after 96 h. The levels detected in the sediment were not significant and may indicate rapid degradation in the water column prior to partitioning to sediment. Environ Toxicol Chem 2017;36:1249-1253. © 2016 SETAC.