Amitraz

Chemical properties

Beige to Pale Yellow Solid

Chemical properties

Amitraz forms colorless needle-like crystals. Liquid formulations may contain flammable organic solvents.

Originator

Aludex,Hoechst Roussel Vet Ltd.

The Uses of Amitraz

Amitraz is an antiparasitic used to control red spider mites, leaf miners and scale insects. This compound is active by inhibiting the targets monoaminooxidase enzyme.

The Uses of Amitraz

coccidiostat, antiplatelet

The Uses of Amitraz

Acaricide; insecticide.

The Uses of Amitraz

Amitraz is used for the control of all stages of mites and insects such as aphids and whitefly, and the eggs and first instar larvae of Lepidoptera on fruit, cotton and vegetables. It is also used in honey bee hives and for the control of ticks, mites and lice on domestic and farm animals.

Definition

ChEBI: A tertiary amino compound that is 1,3,5-triazapenta-1,4-diene substituted by a methyl group at position 3 and 2,4-dimethylphenyl groups at positions 1 and 5.

Manufacturing Process

A mixture of 55.1 g 2,4-dimethylaniline hydrochloride, 83.7 g ptoluenesulphonyl chloride and 150 ml N-methylformamide was stirred with occasional cooling to maintain the temperature at 20°-35°C. When the exothermic reaction had subsided, the mixture was stirred at room temperature for 4 h, poured into a mixture of ice and water, and basified with 10 N sodium hydroxide solution, keeping the temperature of the mixture below 10°C. The precipitated solid was filtered, washed with water until free from alkali, dried at room temperature, to give N-2,4-dimethylphenyl-N'- methylformamidine, melting point 75°-76°C (recrystallized from cyclohexane).
A solution of 19.4 g N-2,4-dimethylphenyl-N'-methylformamidine and 0.3 g ptoluenesulphonic acid in 195 ml dry xylene was refluxed under anhydrous conditions for 48 h, causing the evolution of methylamine. The xylene was distilled off under reduced pressure to give 1,5-di-(2,4-dimethylphenyl)-3- methyl-1,3,5-triaza-penta-1,4-diene, melting point 88°-89°C (crystallized twice from isopropyl).

Therapeutic Function

Acaricide, Scabicide, Tickicide, Appetite stimulant

Toxicity

Amitraz poisoning is frequently encountered in dogs and cats. With dogs, poisoning is most often associated with accidental ingestion of the flea and tick collar, resulting in severe toxicity and sometimes fatal poisoning. In humans, poisoning occurs because of oral ingestion of amitraz. The major signs of acute poisoning are nausea, vomiting, coma, somnolence, miosis or mydriasis, bradycardia, hypo- or hyperthermia, polyuria, and respiratory failure.

Toxicity

Amitraz poisoning is frequently encountered in dogs and cats. With dogs, poisoning is most often associated with accidental ingestion of the flea and tick collar, resulting in severe toxicity and sometimes fatal poisoning. In humans, poisoning occurs because of oral ingestion of amitraz. The major signs of acute poisoning are nausea, vomiting, coma, somnolence, miosis or mydriasis, bradycardia, hypo- or hyperthermia, polyuria, and respiratory failure.

Toxicity

Amitraz poisoning is frequently encountered in dogs and cats. With dogs, poisoning is most often associated with accidental ingestion of the flea and tick collar, resulting in severe toxicity and sometimes fatal poisoning. In humans, poisoning occurs because of oral ingestion of amitraz. The major signs of acute poisoning are nausea, vomiting, coma, somnolence, miosis or mydriasis, bradycardia, hypo- or hyperthermia, polyuria, and respiratory failure.

General Description

White monoclinic crystals. Melting point 187-189°F (86-87°C). Insoluble in water. Used as an acaricide, insecticide and treatment of demodectic mange in dogs.

Air & Water Reactions

Insoluble in water.

Reactivity Profile

Unstable in acid.

Agricultural Uses

Insecticde, Acaricide, Veterinary medicine: Registered for control of pear psylla on pears, whitefly and mites on pears and cotton; cattle, dogs, sheep, and hog dip to control ticks, mange mites, lice and other pests. Not permitted on apples. Used to control red spider mites, leaf miners, scale insects, and aphids. Also used on cotton to control bollworms, white fly, leaf worms, and tobacco budworms. Not registered for use in EU countries

Trade name

AAZDIENO®; ACARAC®; ACADREX®; ARMY®; AZODIENO®; BAAM®; BOOTS BTS 27419®; BTS 27,419®; BUMETRAN®; COYOTE®; DANICUT®; ECTODEX®; EDRIZAN®; EDRIZAR®; GARIAL®; ISTAMBUL®; MITABAN®; MITAC®; OVASYN®; OVIDREX®; PARSEC®; ROTRAZ®; SENDER®; TAC-PLUS®; TACTIK®; TRIATIX®; TRIATOX®; TUDY®; VAPCOZIN TAKTIC®; UPJOHN U-36059®

Pharmacology

The mechanism of action of amitraz has not been completely elucidated, and, presently, a dual mode of action appearsmost likely. Firstly, the enzymemonoamine oxidase, which metabolizes neurotransmitter amines in mites and ticks, is inhibited. Secondly, octopamine receptors in the central nervous system of ectoparasites are activated by amitraz, thereby modifying tonic muscle contractions. The effect of amitraz is to induce increased neuronal activity, abnormal behavior, detachment, and death of mites and ticks.

Potential Exposure

Those engaged in the manufacture, formulation and application of this insecticide and acaricide. A rebuttable presumption against registration for amitraz was issued on April 6, 1977 by United States Environmental Protection Agency on the basis of oncogenicity. Incompatibilities: Keep away from strong oxidizers and strong acids. Acids may render this material unstable.

Veterinary Drugs and Treatments

In dogs, amitraz solution is used topically primarily in the treatment of generalized demodicosis. A topical spot-on solution (ProMeris? for Dogs) and a collar (Preventic?) are available for treatment and prevention of flea and tick infestation. It is also used as a general insecticidal/ miticidal agent in several other species (see label information). The pharmacologic action of amitraz is not well understood, but it is a monoamine oxidase (MAO) inhibitor (in mites) and may have effects on the CNS of susceptible organisms. It apparently also possesses alpha-2 adrenergic activity and inhibits prostaglandin synthesis. Amitraz can cause a significant increase in plasma glucose levels, presumably by inhibiting insulin release via its alpha2-adrenergic activity. Yohimbine (alpha2 blocker) or atipamezole can antagonize this effect.

Metabolic pathway

14C-Amitraz is applied on lemons grown under glasshouse conditions at final harvest and the applied radioactivity is quantitatively recovered, predominantly in the peel (86%). The total residue at harvest contains amitraz, N-methyl-N'-(2,4-xylyl)formamidine, and formyl-2',4'-xylydine and conjugates of 4-amino- m-toluic acid and the conjugated metabolites which are convertible to 2,4-xylidine. Amitraz is readily hydrolyzed at low pH values, forming acid-stable formyl-2,4-xylydine which can be further hydrolyzed to 2,4-xylidine.

Metabolism

Amitraz is poorly absorbed when applied topically to animals. By contrast, orally administered amitraz is rapidly and extensively absorbed. The metabolism and excretion of amitraz are also rapid. It is hydrolyzed to N-(2,4-dimethylphenyl)-N -methyl formamidine and 2,4- dimethyl formamidine and the final product, 4-amino-3- methylbenzoic acid, is converted to non-toxic conjugates. The latter are excreted in the urine and, to a lesser extent, in bile.

Shipping

UN2763 Triazine pesticides, solid, toxic, Hazard Class: 6.1; Labels: 6.1-Poisonous materials.

Degradation

Amitraz is readily hydrolysed at acidic pH but is relatively stable under alkaline conditions. Its DT₅₀ values at 25 °C at pH 5,7 and 9 are given as 2.1,22.1 and 25.5 hours, respectively (PM). A recent study (Pierpoint et aE., 1997) as part of the development of a vat management and waste disposal programme for animal dips describes the kinetics and mechanism of hydrolysis of amitraz in detail. Pseudo-first-order rate constants are given for six pH values between 3.24 and 9.12. The DT₅₀ values at pH values 3.24, 5.09 and 9.12 were respectively 0.4, 8.7 and 112 hours. The reaction was mainly acid-catalysed with a small unassisted component. There was no base catalysis. One of the primary products (Scheme 1) was N-2,4 dimethylphenyl-N-methylformamidine( 2); however, at low pH this was not detected because it was rapidly hydrolysed to 2,4-dimethylphenylformamide (3). Some direct hydrolysis of amitraz to product 3 was also seen. The latter underwent slow base-catalysed hydrolysis to 2,4 dimethylaniline (4). This was a much slower reaction with a DT₅₀ (pH 9.12) of about 300 days.

Toxicity evaluation

Amitraz displays serotonin (5-hydroxytryptamine) blocking activity and a2-adrenoceptor agonist activity in animals. The clinical signs associated with intoxication in dogs include sedation, bradycardia, hypotension, hyperglycaemia, hypothermia, and mydriasis. The specific antidote for animal toxicity is the a2-adrenoceptor antagonist, yohimbine. The toxicity profile of amitraz in the horse includes transient sedation and intestinal stasis that can progress to impaction colic (79). For this reason, amitraz is not approved for use in this species in any country.

Incompatibilities

Those engaged in the manufacture, formulation and application of this insecticide and acaricide. A rebuttable presumption against registration for amitraz was issued on April 6, 1977 by United States Environmental Protection Agency on the basis of oncogenicity. Incompatibilities: Keep away from strong oxidizers and strong acids. Acids may render this material unstable.

Waste Disposal

In accordance with 40CFR 165 recommendations for the disposal of pesticides and pesticide containers. Must be disposed properly by following package label directions or by contacting your local or federal environmental control agency, or by contacting your regional EPA office.