Amitraz

Amitraz (development code BTS27419) is a non systemic acaricide and insecticide and has also been described as a scabicide. It was first synthesized by the Boots Co. in England in 1969. Amitraz has been found to have an insect repellent effect, works as an insecticide and also as a pesticide synergist. Its effectiveness is traced back on alpha adrenergic agonist activity, interaction with octopamine receptors of the central nervous system and inhibition of monoamine oxidases and prostaglandin synthesis. but it is used as a pesticide in many different fields. Therefore, amitraz is available in many different forms, such as a wettable powder, an emulsifiable concentrate, a soluble concentrate/liquid, and an impregnated collar (for dogs). It is characterized as an insect repellent, insecticide, and pesticide synergist. These are the properties which make it especially useful as a pesticide:
The repellent effect causes insects to turn away from their target as this is treated with amitraz. For agricultural purposes amitraz is primarily used to control the pear psylla (Cacopsylla pyricola) on Oregon pear crops and whiteflies and mites on cotton or pear crops. Territorial differences in amitraz use depend on the species of mites that infest the crops/trees/etc., the local practice, and the number and size of the pear trees. An infestation e. g. by Tetranychus spp. requires higher rates of amitraz. Taking those factors into consideration the application volumes of amitraz have been standardized in terms of maximum spray concentration and in the rate of amitraz per hectare. In combination with additional agents it can be used against flea infestation as well. Furthermore, skin or mucosa irritations may occur in dogs as a response to an amitraz containing collar. This can lead to itching, eczema, alopecia or conjunctivitis. Accidental exposure of men to greater amounts of amitraz can lead to death due to respiratory failure, mainly after oral uptake or inhalation. In Turkey during 1989, 41 cases of deadly amitraz intoxications have been detected. Initially it is important to remove the patient from the amitraz contaminated area. When amitraz has been inhaled the patient should first get respiratory protection. Additionally the patient should be supplied with 4 L oxygen per minute. |
| ROWSPAN ="3" | Rat || oral || 400 mg/kg
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| dermal || >1600 mg/kg
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| intraperitoneal || 800 mg/kg
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| ROWSPAN ="2" | Mouse || oral || 1600 mg/kg
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| intraperitoneal || >100 mg/kg
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| ROWSPAN ="2" | Rabbit || oral || >100 mg/kg
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| dermal || >200 mg/kg
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| Baboon || oral || 150–250 mg/kg
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| Dog || oral || 100 mg/kg
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| Guinea pig || oral || 400–800 mg/kg
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Since its discovery by Boots Co. in 1969 three main synthesis routes for amitraz has been developed, which stand out in terms of facility and generality. One of the first amitraz manufacturing plants used this reaction scheme (figure 1). This yields an intermediate, which reacts further as its catalyzed by p toluene acid to N, N' [(methylimino) dimethylidyne] di 2,4 xylidine (amitraz). In rats the metabolic pathway (figure 3) has been examined after oral administration of C labelled amitraz, which was found to be effectively metabolized, degraded and excreted to four of the metabolites in urine and six in faeces. Under basic conditions (pH>6) amitraz is metabolized to 2,4 dimethylphenylformamide. Followed by hydrolysis to 2,4 dimethylaniline, which also benefits from a basic pH. The toxic effects to humans following on amitraz uptake include loss of consciousness, vomiting, respiratory failure, miosis, hypothermia, bradycardia, hyperglycemia and central nervous system depression. When an amitraz poisoning is lethal, death results from respiratory depression. Xylene present in amitraz formulations additionally induces central nervous system depression. Consequently, a dose dependent delay of gastrointestinal transit in conscious mice occurs. This effect could be antagonized by alpha2 adrenergic blocking agents, but administration of other antagonists did not reduce the depressant effect on the gastrointestinal transit. This interaction is probably the reason for increased nervous activity of ticks as a response on amitraz. Usual activation of the receptors may lead to changes in the concentration of intracellular second messengers such as cyclic nucleotides cyclic AMP (cAMP) and cyclic GMP, inositol 1,4,5 trisphosphate and Ca2+. Influencing this signal transduction system can lead to various events depending on the celltype. However, in vivo it has been observed that only at high doses of amitraz or its main metabolite N 2,4 dimethylphenyl N methyl formamide monoamine oxidase inhibition occurs. In a dose of 5 to 80 mg/kg body weight, given intraperitoneally to rats, amitraz reduces yeast induced fever and antagonizes the carrageenin induced swelling of the hind paw. Some of the physiological effects of amitraz probably go back to this aspirin like activity and occur due to inhibition of prostaglandin synthesis.