Characterization of the antinociceptive and sedative effect of amitraz in horses

Abstract

Amitraz, an acaricide used to control ectoparasites in animals has a complex pharmacological activity, including alpha2-adrenergic agonist action. The purpose of this research was to investigate the possible antinociceptive and/or sedative effect of amitraz in horses. The sedative effect of the intravenous (i.v.) injection of dimethylformamide (DMF, 5 mL, control) or amitraz (0.05, 0.10, 0.15 mg/kg), was investigated on the head ptosis test. The participation of alpha2-adrenergic receptors in the sedative effect provoked by amitraz was studied by dosing yohimbine (0.12 mg/kg, i.v.). To measure the antinociception, xylazine hydrochloride (1 mg/kg, i.v., positive control) and the same doses of amitraz and DMF were used. A focused radiant light/heat directed onto the fetlock and withers of a horse were used as a noxious stimulus to measure the hoof withdrawal reflex latency (HWRL) and the skin twitch reflex latency (STRL). The three doses of amitraz used (0.05, 0.10 and 0.15 mg/kg) provoked a dose-dependent relaxation of the cervical muscles. The experiments with amitraz and xylazine on the HWRL showed that after i.v. administration of all doses of amitraz there was a significant increase of HWRL up to 150 min after the injections. Additionally, there was a significant difference between control (DMF) and positive control (xylazine) values up to 30 min after drug injection. On the other hand, the experiments on the STRL show that after administration of amitraz at the dose of 0.15 mg/kg, a significant increase in STRL was observed when compared with the control group. This effect lasted up to 120 min after injection. However, no significant antinociceptive effect was observed with the 0.05 and 0.10 mg/kg doses of amitraz or at the 1.0 mg/kg dose of xylazine.

Comparação dos efeitos da romifidina e de uma emulsão de amitraz na sedação e na atividade locomotora espontânea de eqüinos

“…Despite several authors' statements that amitraz is an alpha-2 agonist drug 12,13,14,17,18 , there are no pharmacological studies that establish its specificity to this receptor. Thus, a clinical comparison between amitraz and romifidine, which is a potent alpha-2 agonist 24,25 , is proposed as an efficient method to establish possibilities of using amitraz as an intense and long lasting sedative for horses.…”

“…12,13,14,15,16,17 These effects could provide an indication for the use of amitraz for sedation practices in veterinary medicine, and this might be particularly appealing in horses because of its low price and its potential analgesic and muscle relaxing effects. 18 Considering the well known effects of romifidine on horses, mediated by its highly specific action on alpha-2 adrenoceptors, this behavioral study proposes to compare its sedative effects with those induced by an emulsion of amitraz, in order to determine the possibility of using this drug as a sedative for horses.…”

Intoxicações natural e experimental por amitraz em eqüídeos: aspectos clínicos

“…O mesmo antagonista reduziu significativamente efeitos referentes ao SNC, tais como sonolência, ataxia e parada da mastigação (Roberts & Argenzio 1986). Vários autores afirmam que a administração de antagonistas a 2 -adrenérgicos como a ioimbina e o atipamezole são capazes de reverter os efeitos provocados pelo amitraz Hovda & McManus 1993, Duncan 1993, Pass & Mogg 1995, Hugnet & Cadoré 1995, Hugnet et al 1996, Harkins et al 1997, Queiroz-Neto et al 1998. Desta maneira, parece bem clara a função agonista a 2 -adrenérgica exercida pelo acaricida.…”

“…Devemos ressaltar que quando excluímos da discussão de possíveis locais de lesões a junção neuro-efetora e aos respectivos músculos, o fizemos por evidenciar clinicamente que estes locais não foram afetados, uma vez que os animais manifestaram alterações do estado de consciência, o que não ocorre nas doenças que afetam a junção neuro-efetora como o botulismo, e não mostraram sinais de doença muscular (Radostits et al 2002). A postura em estação com a cabeça baixa, provocada por um relaxamento da musculatura cervical (Queiroz-Neto et al 1998) pode originar-se, em nossa opinião, de um distúrbio da propriocepção geral da região cervical. Este distúrbio também pode ser a causa da postura com a cabeça apoiada no solo, quando em decúbito esternal.…”

“…Esta manifestação foi descrita como um dos efeitos menos importantes das drogas agonistas a 2 -adrenérgicas (England & Clarke 1996), grupo do qual, comprovadamente, o amitraz faz parte (Sellers et al 1984, Roberts & Argenzio 1986, Hovda & McManus 1993, Duncan 1993, Pass & Mogg 1995, Hugnet & Cadoré 1995, Hugnet et al 1996, Harkins et al 1997, Queiroz-Neto et al 1998. Esta alteração tem sido associada à utilização de drogas do grupo das fenotiazinas, que causam bloqueio dos receptores a 1 (Speirs 1999).…”