Sodium channel-directed alkaloids synergize the mosquitocidal and neurophysiological effects of natural pyrethrins

Authors: Norris, Edmund; BLOOMQUIST, JEFFREY - University Of Florida

Submitted to: Pesticide Biochemistry and Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/5/2022
Publication Date: 7/9/2022
Citation: Norris, E.J., Bloomquist, J.R. 2022. Sodium channel-directed alkaloids synergize the mosquitocidal and neurophysiological effects of natural pyrethrins. Pesticide Biochemistry and Physiology. https://doi.org/10.1016/j.pestbp.2022.105171.
DOI: https://doi.org/10.1016/j.pestbp.2022.105171

Interpretive Summary: We explored the potential of two sodium channel activators, veratrine and aconitine, as both insecticides and synergists of natural pyrethrins (NP) on Aedes aegypti adults and larvae. Aconitine was more toxic than veratrine, on pyrethroid-susceptible Orlando strain, and only aconitine showed significant resistance in the pyrethroid-resistant strain. When applied in mixtures of PBO and natural pyrethrins, both alkaloids synergized NP to differing degrees depending on the bioassay type (topical application versus larvaciding). Less synergism was observed on the pyrethroid-resistant strain. When both alkaloids were directly applied alone to the central nervous system of mosquito larvae, veratrine was equipotent on both strains whereas considerable resistance was observed to aconitine in the pyrethroid-resistant strain of Ae. aegypti. Veratrine was capable of synergizing NP nerve blocking effects on both strains, while aconitine only synergized this effect of NP on the pyrethroid-susceptible strain. These results highlight the potential of site II sodium channel activators as insecticides and their ability to synergize pyrethroids.

Technical Abstract: We explored the potential of two sodium channel activators, veratrine and aconitine, as both insecticides and synergists of natural pyrethrins on Aedes aegypti adults and larvae. Aconitine was more toxic than veratrine, with an LD50 of 157 ng/mg compared to 376 ng/mg, on the pyrethroid-susceptible Orlando strain, and only aconitine showed significant resistance in the pyrethroid-resistant Puerto Rico strain (RR = 14.6 in topical application and 8.8 in larval bioassay). When applied in mixtures with piperonyl butoxide (PBO) and natural pyrethrins, large synergism values were obtained on the Orlando strain. Aconitine + PBO mixture synergized natural pyrethrins 21.8-fold via topical adult application and 10.2-fold in larval bioassays, whereas veratrine + PBO synergized natural pyrethrins 5.3-fold via topical application and 30.5-fold in larval bioassays. Less synergism of natural pyrethrins was observed on the resistant Puerto Rico strain, with acontine + PBO synergizing natural pyrethrins only 4.1-fold in topical application (8-fold in larval bioassays) and veratrine + PBO synergizing natural pyrethrins 9.5-fold in topical application (13.3-fold in larval bioassays). When alkaloids were applied directly to the mosquito larval nervous system, veratrine was equipotent on both strains, while aconitine was less active on pyrethroid-resistant nerve preparations (block at 100 µM compared to 1 µM on the susceptible strain). The nerve blocking effect of NP was significantly synergized by both compounds on the pyrethroid-susceptible strain by about 10-fold, however only veratrine synergized NP block on the pyrethroid-resistant strain, also showing 10-fold synergism). These results highlight the potential of site II sodium channel activators as insecticides and their ability to synergize pyrethroids.