Triazapentadiene (Amitraz) Toxicosis in Animals

ByRamesh C. Gupta, DVM, PhD, DABT, FACT, FACN;Robin B. Doss
Reviewed/Revised Aug 2022

The triazapentadiene class includes amitraz (N,N’-[methylimino)dimethylidyne]di-2,4-xylidine), a broad-spectrum insecticide and acaricide.

Many formulations such as wettable powder, emulsified concentrate, soluble concentrate or liquid, or impregnated collar (for dogs) are available for insecticidal purposes. Amitraz is widely used against ticks, mites, and lice found on cattle, sheep, goats, pigs, and dogs. It is not recommended for use in horses, cats, and small-breed dogs such as Chihuahuas and Pomeranians. Amitraz should also not be used in diabetic animals because it adversely affects glucose and insulin concentrations even if it is used topically. Tick collars for dogs contain 9% amitraz, and dip solutions for cattle and sheep contain 12.5%–20% amitraz as an active ingredient.

Amitraz is absorbed rapidly following dermal or oral administration due to its highly lipophilic property. When administered orally in mice, rats, dogs, baboons, and humans, 53%–80% of amitraz is excreted in the urine within 24 hours. The metabolism of amitraz is quite similar in rats, mice, cats, dogs, baboons, cows, and humans. The end product of amitraz is 4-amino-3-methylbenzoic acid, which is rapidly conjugated and excreted.

The oral LD50 of amitraz in rats is 500–600 mg/kg, in mice it is >1,600 mg/kg, and in dogs it is 100 mg/kg. Its dermal LD50 is rats is >1,600 mg/kg and in rabbits it is >200 mg/kg. Acute amitraz poisonings are mostly encountered in dogs and cats due to accidental ingestion of tick collars. Clinical signs typically appear within 30 minutes to 2 hours after ingestion. Dogs with a plasma concentration of 5 mg/L usually show clinical signs of toxicosis.

Amitraz produces toxicity in insects by stimulating the octopamine (neurotransmitter) receptors. In mammals, octopamine resembles the neurotransmitter norepinephrine. Amitraz also produces toxicity in mammals by multiple mechanisms, as it stimulates alpha2-adrenergic receptors, inhibits intracellular adenylate cyclase enzyme, and decreases cAMP concentration. In addition, amitraz blocks histamine (H1) receptors and inhibits monoamine oxidase (MAO) enzyme activity. Amitraz causes a major decrease in serotonin, noradrenaline, and dopamine concentrations in the brain. Inhibition of prostaglandins is also noted.

Clinical signs of toxicosis include hypotension, hypothermia, bradycardia, convulsions, mydriasis, CNS and respiratory depression, lethargy, ataxia, hypersalivation, anorexia, vomiting, hyperglycemia, and gastrointestinal disorders in animals. Dogs may develop cutaneous or mucosal irritations, itching, eczema, alopecia, or conjunctivitis from collars containing amitraz.

Diagnosis is based on residue found in the stomach content, body tissue, or fluid and clinical signs. Untreated animals become comatose or die due to respiratory failure. With a sublethal exposure to amitraz, animals may recover in 7–10 days.

Following oral intake of amitraz, patients with mild signs are treated with supportive care. If mild signs are observed after topical application, washing the skin with plenty of warm water is sufficient. If broken pieces of an amitraz-containing collar are ingested, vomiting should be induced immediately, followed by oral administration of activated charcoal. With moderate to severe signs, patients should be treated with a specific alpha-2-adrenergic receptor antagonist (atipamezole or yohimbine).

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