Amitraz: mechanism of action and toxicity

General Description

Amitraz is an acaricide that binds to octopamine receptors in the nervous system of pests, disrupting their normal functioning and leading to paralysis, feeding inhibition, and reproductive impairment. In cases of amitraz poisoning in humans and animals, symptoms such as central nervous system depression, pupil constriction or dilation, seizures (less common), and rarely reported neurological abnormalities like ataxia, hallucinations, and hypotonia can occur. Amitraz poisoning can also affect the cardiovascular, respiratory, gastrointestinal, and metabolic systems, causing symptoms such as bradycardia, hypotension, respiratory depression, vomiting, asymptomatic liver transaminase elevation, and hyperglycemia. The case fatality rate is low with proper medical attention and treatment.

Figure 1. Biovet of amitraz

Mechanism of action

Amitraz is an acaricide that is widely used in veterinary medicine and agriculture. It belongs to the class of formamidine pesticides and is effective against a variety of pests, including ticks, mites, and insects. The mechanism of action of Amitraz involves its interaction with specific receptors in the nervous system of the target pests. These receptors, known as octopamine receptors, are responsible for regulating various physiological processes in insects and arachnids. When Amitraz is applied, it binds to these receptors and acts as an agonist, stimulating them. This results in the disruption of the normal functioning of the nervous system. The overstimulation of octopamine receptors leads to a cascade of physiological effects, including paralysis, feeding inhibition, and reproductive impairment. Furthermore, Amitraz also inhibits the activity of certain enzymes involved in the metabolism of the target pests. This further contributes to its pesticidal properties. It is important to note that while Amitraz is highly effective against pests, it is relatively safe for mammals, including humans and domestic animals, when used according to recommended guidelines. However, proper precautions should always be taken during handling and application to minimize any potential risks. ¹

Toxicity

Effects on the nervous system

In cases of amitraz poisoning, the most common neurological abnormality observed is central nervous system (CNS) depression. Symptoms such as sleepiness, drowsiness, or even loss of consciousness can occur depending on the amount of toxin consumed. The duration of CNS depression tends to be positively correlated with the dose taken. However, it is important to note that nearly all patients regain consciousness within 48 hours due to the relatively short elimination half-life of the toxin. If altered sensorium persists beyond this timeframe, other potential causes should be investigated. Cerebral edema, evidenced by brain imaging, has been documented in some studies. Seizures were reported in less than one-third of the patients. Amitraz exposure can lead to pupil constriction at lower doses and dilation at higher doses, indicating different mechanisms of action. Both miosis (constricted pupils) and mydriasis (dilated pupils) may occur in the same patient at different times. Rare neurological impairments such as ataxia, hallucinations, and hypotonia have been infrequently reported. In summary, amitraz poisoning primarily manifests as CNS depression, with varying degrees of sleepiness or loss of consciousness. Other symptoms include pupil constriction or dilation, seizures (less common), and rarely reported neurological abnormalities like ataxia, hallucinations, and hypotonia. ²

Others

Amitraz poisoning can affect various bodily systems, including the cardiovascular, respiratory, gastrointestinal, and metabolic systems. Bradycardia and hypotension were common cardiovascular manifestations, primarily due to the stimulation of presynaptic α2-adrenergic receptors. Respiratory depression occurred in over one-third of cases, with some patients requiring mechanical ventilation. Vomiting and asymptomatic liver transaminase elevation were common gastrointestinal symptoms. Hyperglycemia was a distinctive feature, observed in nearly half of the patients. The case fatality rate was low, with only six deaths reported, and only one death could be attributed directly to the poison. Other deaths were caused by unrelated conditions, such as pulmonary thromboembolism and ventilator-associated pneumonia. Overall, amitraz poisoning can cause potentially life-threatening symptoms, but prompt medical attention and appropriate treatment can result in favorable outcomes. ³

Reference

1. Guo L, Fan XY, Qiao X, Montell C, Huang J. An octopamine receptor confers selective toxicity of amitraz on honeybees and Varroa mites. Elife. 2021 Jul 12;10:e68268.

2. Demirel Y, Yilmaz A, Gursoy S, Kaygusuz K, Mimaroglu C. Acute amitraz intoxication: retrospective analysis of 45 cases. Hum Exp Toxicol. 2006 Oct;25(10):613-617.

3. Dhooria S, Agarwal R. Amitraz, an underrecognized poison: A systematic review. Indian J Med Res. 2016 Sep;144(3):348-358.

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