COLLIER H O, SHORLEY P G
Br J Pharmacol Chemother. 1963 Apr;20(2):345-51. doi: 10.1111/j.1476-5381.1963.tb01473.x.
In the guinea-pig, N-(2,3-xylyl)anthranilic acid (mefenamic acid) and N-(alpha,alpha,alpha-trifluoro-m-tolyl)anthranilic acid (flufenamic acid), two new anti-inflammatory agents, antagonize bronchoconstriction, but not hypotension, produced by kinins. They do not reduce bronchoconstrictor responses to acetylcholine, histamine or 5-hydroxytryptamine. The antibradykinin potencies of mefenamic and flufenamic acids approximately equal that of acetylsalicylic acid when given intravenously and of phenylbutazone when given into the duodenum. After administration of mefenamic and flufenamic acids, the bronchoconstrictor response can be restored by higher doses of bradykinin. The quantitative relationship between the intravenous dose of sodium mefenamate or flufenamate and the dose of bradykinin needed to surmount either antagonist in bronchial muscle fulfils the requirements for competitive antagonism. Antagonism by calcium acetylsalicylate can also be surmounted with higher doses of bradykinin, but in this instance the relationship of antagonist to agonist fulfils requirements for competitive antagonism only at the lower part of the dose range.
在豚鼠中，两种新型抗炎药N-（2,3-二甲苯基）邻氨基苯甲酸（甲芬那酸）和N-（α，α，α-三氟间甲苯基）邻氨基苯甲酸（氟芬那酸）可拮抗激肽引起的支气管收缩，但不拮抗低血压。它们不会降低对乙酰胆碱、组胺或5-羟色胺的支气管收缩反应。静脉注射时，甲芬那酸和氟芬那酸的抗缓激肽效力与乙酰水杨酸大致相当，十二指肠给药时与保泰松大致相当。给予甲芬那酸和氟芬那酸后，更高剂量的缓激肽可恢复支气管收缩反应。在支气管肌肉中，甲芬那酸钠或氟芬那酸钠的静脉剂量与克服拮抗剂所需的缓激肽剂量之间的定量关系符合竞争性拮抗的要求。乙酰水杨酸钙的拮抗作用也可被更高剂量的缓激肽克服，但在这种情况下，拮抗剂与激动剂的关系仅在剂量范围的较低部分符合竞争性拮抗的要求。
