Antagonism of picumast and ketotifen against histamine, acetylcholine, LTC4, slow-reacting substance of anaphylaxis and barium chloride in the guinea pig ileum bioassay.

The antagonism of the antiallergic compounds picumast (PIC; Boehringer Mannheim) and ketotifen (K; Sandoz) against pro-allergic mediators like histamine (H), acetylcholine (ACh), SRS-A and LTC4 as well as against the unspecific spasmogen BaCl2 was compared in the bioassay of superfused guinea pig ileum. For the evaluation of an SRS-A antagonism crude SRS-A from antigen-stimulated guinea pig lung fragments in Krebs buffer was used with the addition of atropine and mepyramine. PIC (approximately 10(-6)-10(-5) mol/l) antagonized clearly all tested spasmogens in a concentration-dependent manner. Its predominant antagonism (IC30: 2-3 X 10(-6) mol/l) was against H, LTC4 and SRS-A, which are presumably important mediators of allergic reactions. ACh- or BaCl2-induced spasms were inhibited to the same extent with a 4 or 6 times higher concentration of PIC. K was approximately 20 times more potent as antagonist against H and approximately 8 times more potent against ACh, whereas the antagonism against LTC4- or BaCl2-induced spasms reached only 1/3 of that of PIC. An antagonism of PIC against SRS-A, LTC4 and H may contribute to its antiallergic activity in vivo. K showed little activity against LTC4 but could antagonize more selectively H- and ACh-mediated effects.