Antagonism by fenamates and like‐acting drugs of bronchoconstriction induced by bradykinin or antigen in the guinea‐pig

Abstract

1 Nine non-steroidal anti-inflammatory drugs were tested for antagonism of bradykinin-induced bronchoconstriction in guinea-pig lungs in vivo. Only one, benzydamine, was inactive. 2 The descending order of potency of the active anti-inflammatory drugs was meclofenamate = Scha 306>Scha 87/2>indoxole>Mi85>indomethacin>glafenine>ibufenac. 3 Of eight other drugs tested, chlorpromazine, phenoxybenzamine and four others were inactive, whereas phenelzine and mebanazine possessed activity. 4 In tests at two dose-levels of meclofenamate, the dose-ratio of bradykinin increased proportionately with the dose of meclofenamate. 5 The anti-bradykinin effect of meclofenamate was still observed after destruction of the brain and spinal cord, after bilateral adrenalectomy or after blockade of β-receptors for adrenaline. 6 Meclofenamate did not release catecholamines from the adrenal medulla or prevent such a release by bradykinin given intra-arterially. 7 The fenamates and like-acting drugs reduced the intensity of anaphylactic bronchoconstriction in guinea-pigs treated with mepyramine or propranolol. The descending order of potency was meclofenamate>flufenamate>mefenamate. 8 Dose/response curves for the antagonism of anaphylactic bronchoconstriction by the fenamates, in the presence of propranolol, turned downwards at high doses. 9 These findings suggest that the fenamates may find a useful place in the treatment of bronchial asthma or other conditions involving allergic ventilatory impairment.