Target identification and acaricidal activity difference of amitraz and its metabolite DPMF in Tetranychus cinnabarinus (Boisduval)

Abstract

BACKGROUND Amitraz is a broad‐spectrum formamidine acaricide proven to be effective against mites in all development stages. Under acidic conditions, amitraz is hydrolyzed to N2‐(2,4‐dimethylphenyl)‐N1‐methyformamidine (DPMF), an active metabolite for mite control. Octopamine and tyramine receptors are well known targets of amitraz. Until now, no research has been conducted about the amitraz target in Tetranychus cinnabarinus. This study aimed to identify the target genes of amitraz in T. cinnabarinus and reveal the mechanisms behind the differential acaricidal activities of amitraz and DPMF. RESULTS Analysis of the toxicity, stress expression, target sensitivity and binding site of amitraz against T. cinnabarinus showed that TcOctβ2R was the main target gene of amitraz. DPMF had more potent acaricidal activity against T. cinnabarinus and was more effective at activating TcOctβ2R than amitraz. Furthermore, the three synergists had no significant effect on amitraz and DPMF, indicating that the detoxification metabolism was not related to the difference in acaricidal activity. CONCLUSION In this study, TcOctβ2R was identified as the main target gene of amitraz against T. cinnabarinus. The divergence of target binding was responsible for the difference in acaricidal activity between amitraz and DPMF. The results also revealed the physiological and pharmacological functions of octopamine receptors (OARs) in T. cinnabarinus and could provide a basis for the design of new acaricides, with OARs as a special target. © 2023 Society of Chemical Industry.

Contrasting roles of cytochrome P450s in amitraz and chlorfenapyr resistance in the crop pest Tetranychus urticae

“…CYP392A16 metabolized amitraz with high efficacy to a hydroxylated metabolite. Although the exact site and metabolite structure could not be resolved, we confirmed that the structure is different from DPMF, the known toxic metabolite of amitraz (Cai et al, 2023;Kita et al, 2017). This implies that CYP392A16 is able to metabolize amitraz, although further toxicological analysis of the metabolite is still required.…”

“…Amitraz is a formamidine pro-pesticide belonging to IRAC Group 19 (Hollingworth, 1976;Sparks et al, 2021). Amitraz can act as an agonist by stimulating the β-adrenergic-like octopamine receptors (βAOR), but its active metabolite, DPMF (N 2 -(2,4-dimethylphenyl)-N 1 -methylformamidine), is an even stronger agonist (Cai et al, 2023;Kita et al, 2017;Takata et al, 2020). Important to note is the observed strong connection from toxicity bioassays between chlorfenapyr and amitraz resistance in T.…”