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ANTAGONISM BY MEFENAMIC AND FLUFENAMIC ACIDS OF THE BRONCHOCONSTRICTOR ACTION OF KININS IN THE GUINEA‐PIG
Author(s) -
COLLIER H. O. J.,
SHORLEY PATRICIA G.
Publication year - 1963
Publication title -
british journal of pharmacology and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0366-0826
DOI - 10.1111/j.1476-5381.1963.tb01473.x
Subject(s) - antagonism , flufenamic acid , guinea pig , mefenamic acid , pharmacology , chemistry , bradykinin , sympathomimetics , medicine , endocrinology , biochemistry , receptor
In the guinea‐pig, N ‐(2,3‐xylyl)anthranilic acid (mefenamic acid) and N ‐(α,α,α‐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.