ANTAGONISM BY FENAMATES OF PROSTAGLANDIN ACTION IN GUINEA‐PIG AND HUMAN ALIMENTARY MUSCLE

Abstract

1 Low concentrations of meclofenamate, flufenamate or mefenamate had little effect on contractions in response to acetylcholine in any tissue studied. 2 Sodium meclofenamate potently antagonized contractions of guinea-pig ileum longitudinal muscle to prostaglandin E₂ (PGE₂), PGF_2α or PGD₂. 3 In guinea-pig colonic longitudinal muscle, contractions to PGE₂ were reduced by sodium meclofenamate, but contractions of the longitudinal or circular muscle to PGF_2α or PGD₂ were less effectively inhibited. 4 In human gastrointestinal longitudinal muscle, sodium meclofenamate or flufenamate potently inhibited contractions to PGF_2α, but not to PGE₂. 5 Sodium mefenamate or mefenamic acid, even in high concentrations, had little effect on contractions to PGF_2α, but tended to inhibit PGE₂-induced contractions of human gastrointestinal longitudinal muscle. 6 The therapeutic advantages of prostaglandin synthesis inhibitors which also antagonize responses to certain prostaglandins are discussed.