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.
D000109:Acetylcholine / Q000037:antagonists & inhibitors*; D000818:Animals; D001464:Barium / Q000037:antagonists & inhibitors*; D017609:Barium Compounds; D002712:Chlorides; D003374:Coumarins / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects; D007665:Ketotifen / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D013189:SRS-A / Q000037:antagonists & inhibitors*
D017609:Barium Compounds; D002712:Chlorides; D003374:Coumarins; D006633:Histamine Antagonists; D013189:SRS-A; C024986:barium chloride; C013373:picumast; D001464:Barium; D000109:Acetylcholine; D007665:Ketotifen