Khalili-Varasteh H, Rosner I, Legros J
Arch Int Pharmacodyn Ther. 1976 Jan;219(1):149-59.
The simlutaneous oral administration of benorylate (4-(acetamido) phenyl 2-acetoxybenzoate) with either indomethacin or phenylbutazone to rats suffering from Freund's adjuvant-induced arthritis leads to an anti-inflammatory effect which is significantly greater than the effect of the same drugs administered alone. Such an additive anti-inflammatory effect is not apparent when the metabolites of benorylate (paracetamol, acetylsalicylic acid) are administered with indomethacin or phenylbutazone. Paracetamol does not increase the anti-inflammatory effect of indomethacin or phenylbutazone and acetylsalicylic acid clearly antagonizes it. The molecule of benorylate itsel is therefore responsible for the additive anti-inflammatory effect. However, if antipyretic activity (yeast-induced hyperthermia) is examined instead of anti-inflammatory activity, the simultaneous oral administration of the different drugs always produces an additive effect. It is concluded that the antagonism between indomethacin or phenylbutazone and non-steroidal anti-inflammatory drugs other than benorylate is present at some receptors but not all. The clinical implications of the results are discussed.
对弗氏佐剂诱导的关节炎大鼠同时口服贝诺酯（4-（乙酰氨基）苯基 2-乙酰氧基苯甲酸酯）与吲哚美辛或保泰松，会产生比单独给予相同药物显著更强的抗炎作用。当贝诺酯的代谢产物（对乙酰氨基酚、乙酰水杨酸）与吲哚美辛或保泰松同时给药时，这种相加的抗炎作用并不明显。对乙酰氨基酚不会增强吲哚美辛或保泰松的抗炎作用，而乙酰水杨酸则明显拮抗这种作用。因此，贝诺酯分子本身导致了相加的抗炎作用。然而，如果检测的是解热活性（酵母诱导的体温过高）而非抗炎活性，同时口服不同药物总是会产生相加作用。得出的结论是，吲哚美辛或保泰松与除贝诺酯之外的非甾体抗炎药之间的拮抗作用存在于某些受体而非全部受体。文中讨论了这些结果的临床意义。
