Hugnet C, Buronrosse F, Pineau X, Cadoré J L, Lorgue G, Berny P J
Centre National d'Informations Toxicologiques Veterinaires, Ecole Nationale Vétérinaire de Lyon, France.
Am J Vet Res. 1996 Oct;57(10):1506-10.
To evaluate the toxic effects of amitraz in dogs and their reversal by various doses of atipamezole.
6 male 1-year-old Beagles.
Dogs were given 100 mg of amitraz/kg of body weight, PO. Atipamezole was administered at 3 dose rates. Clinical examination and blood sample collection were performed regularly for 48 hours to examine biological parameters and determine the toxicokinetics of amitraz as well as the efficacy of the antidote. A specific high-performance thin layer chromatographic method was developed to determine plasma amitraz concentrations.
Clinical signs of toxicosis included sedation, bradycardia, polyuria, hypothermia, and hyperglycemia, all of which could be related to the alpha 2-agonist activity of amitraz, and were reversed by low doses of atipamezole (50 micrograms/kg, IM), a potent alpha 2-antagonist, within 10 minutes after injection. Peak plasma concentrations were observed after 5 hours, and the elimination half-life was long (about 24 hours).
All clinical and biological effects observed during the course of amitraz poisoning could be attributed to the parent compound itself and were reversed by low doses of atipamezole. The half-life of amitraz was substantially longer than that in other studies because of the high dose administered.
Atipamezole can be administered i.m. to dogs with severe amitraz poisoning to reverse all the effects observed.
评估双甲脒对犬的毒性作用以及不同剂量阿替美唑对其的解毒效果。
6只1岁雄性比格犬。
给犬口服100mg双甲脒/千克体重。以3种剂量率给予阿替美唑。在48小时内定期进行临床检查和采集血样，以检测生物学参数、确定双甲脒的毒代动力学以及解毒剂的疗效。开发了一种特定的高效薄层色谱法来测定血浆双甲脒浓度。
中毒的临床症状包括镇静、心动过缓、多尿、体温过低和高血糖，所有这些都可能与双甲脒的α2-激动剂活性有关，并且在注射后10分钟内被低剂量的阿替美唑（50微克/千克，肌肉注射）逆转，阿替美唑是一种有效的α2-拮抗剂。5小时后观察到血浆浓度峰值，消除半衰期较长（约24小时）。
双甲脒中毒过程中观察到的所有临床和生物学效应都可归因于母体化合物本身，并被低剂量的阿替美唑逆转。由于给药剂量高，双甲脒的半衰期比其他研究中的长得多。
对于严重双甲脒中毒的犬，可肌肉注射阿替美唑以逆转观察到的所有效应。
