Sancilio L F, Cheung S
J Pharmacol Exp Ther. 1978 Nov;207(2):469-75.
Dogs respond to bradykinin (triacetate) by struggling, vocalizing, and/or biting. In 128 dogs used twice, the threshold dose of the peptide increased more than 2-fold, while its onset and duration of action were unchanged. In both trials, the frequency distribution of the threshold dose was not normal; struggling occurred alone or with vocalization and/or biting in 95% of the animals in the first trial and in 96% of the animals in the second trial. In assaying analgesic drugs for antibradykinin activity, multiples of the threshold dose of the peptide were given after oral administration to compensate for tachphylaxis. The oral ED50 values (95% confidence limits) were 0.80 (0.50--1.06) mg/kg for d-amphetamine, 1.20 (0.63--2.57) mg/kg for indomethacin, 1.90 (0.50--6.48) mg/kg for methadone, 15.0 (8.0--30.9) mg/kg for phenylbutazone and 50.0 (20.0--120.0) mg/kg for acetylsalicylic acid. ED50 values for d-proproxyphene, codeine, meperidine, pentazocine and ethoheptaxine by the oral route could not be determined. The intravenous ED50 (95% confidence limits) of meperidine was 0.80 (0.30--1.90 mg/kg. The antibradykinin model in dogs is sensitive to orally administered acetylsalicylic acid-type analgesic compounds which may be a reflection of their prostaglandinsynthetase inhibiting properties.
狗对缓激肽(三乙酸盐)会有挣扎、吠叫和/或咬人的反应。在128只被使用两次的狗中,该肽的阈剂量增加了两倍多,而其起效时间和作用持续时间未变。在两项试验中,阈剂量的频率分布都不正常;在第一次试验中,95%的动物单独出现挣扎,或伴有吠叫和/或咬人,在第二次试验中,96%的动物出现这种情况。在测定镇痛药的抗缓激肽活性时,口服该肽阈剂量的倍数以补偿快速耐受性。口服ED50值(95%置信限)分别为:右旋苯丙胺0.80(0.50 - 1.06)mg/kg、吲哚美辛1.20(0.63 - 2.57)mg/kg、美沙酮1.90(0.50 - 6.48)mg/kg、保泰松15.0(8.0 - 30.9)mg/kg、乙酰水杨酸50.0(20.0 - 120.0)mg/kg。右旋丙氧芬、可待因、哌替啶、喷他佐辛和依托庚嗪的口服ED50值无法确定。哌替啶的静脉注射ED50(95%置信限)为0.80(0.30 - 1.90)mg/kg。狗的抗缓激肽模型对口服的乙酰水杨酸类镇痛药敏感,这可能反映了它们抑制前列腺素合成酶的特性。