Analysis of the bradykinin response in dogs and its antagonism by analgesic drugs.

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.