Reference

Antiallergic action of amoxanox (AA-673), its main metabolite M-I and tranilast

Antiallergic action of amoxanox (AA-673), its main metabolite M-I and tranilast. Kuriki, Hisashi; Saijo, Taketoshi; Ashida, Yasuko; Makino, Haruhiko; Maki, Yoshitaka (Cent. Res. Div., Takeda Chem. Ind., Ltd., Japan). Yakuri to Chiryo, 13(11), 6435-46 (Japanese) 1985. CODEN: YACHDS. ISSN: 0386-3603.Several substances with their cas registry numbers 53902-12-8 and 100157-23-1 may be metioned in this study. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The effects of amoxanox (I) [68302-57-8], its main metabolite (M-I) (II) [100157-23-1] and tranilast (III) [53902-12-8] on exptl. allergic reactions were investigated. I inhibited IgE-mediated bronchoconstriction and the PCA reaction in rats, IgG1-mediated and leukotriene D4 (LTD4)-induced bronchoconstriction in guinea pigs, IgE-mediated histamine release from rat mast cells, immunol. stimulated generation of leukotrienes in guinea pig lung, and the contractile response of guinea pig lung to LTD4. II inhibited the IgE-mediated bronchoconstriction and the histamine release with a potency identical to that of I, but showed little effect on the IgG1-mediated and LTD4-induced bronchoconstriction and the generation of leukotrienes. The pharmacol. profile of III was similar to but less potent than that of I except that it did not suppress the LTD4-induced bronchoconstriction and the generation of leukotrienes. .

Mechanism of action of an antiallergic agent, amlexanox (AA-673), in inhibiting histamine release from mast cells

Mechanism of action of an antiallergic agent, amlexanox (AA-673), in inhibiting histamine release from mast cells. Acceleration of cAMP generation and inhibition of phosphodiesterase. Makino, H.; Saijo, T.; Ashida, Y.; Kuriki, H.; Maki, Y. (Cent. Res. Div., Takeda Chem. Ind., Ltd., Osaka 532, Japan). Int. Arch. Allergy Appl. Immunol., 82(1), 66-71 (English) 1987. CODEN: IAAAAM. ISSN: 0020-5915. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Amlexanox (I) [68302-57-8] markedly inhibits histamine [51-45-6] release from rat mast cells. To clarify the mechanism of this inhibition, the effect of amlexanox on cAMP [60-92-4] content of rat peritoneal mast cells was investigated. At 10-8-10-6M, amlexanox or isoproterenol increased the cAMP content of mast cells over that of control cells about 2-fold. When the mast cells were incubated with 10-8, 10-7, and 10-6M isoproterenol, the cAMP contents were synergistically increased 15-, 60- and 88-fold, resp. 60-92-4 and 51-45-6 are also in the experiment. 3-Isobutyl-1-methylxanthine (IBMX) [28822-58-4] at 10-6-10-4M increased the cAMP content 1.7-3.8-fold, and a combination of 10-4M IBMX and 10-7M isoproterenol synergistically increased the cAMP content 41-fold. A combination of amlexanox and IBMX synergistically increased the cAMP content 19-fold. The increase in cAMP content, when amlexanox and isoproterenol were combined, was transient. Pretreatment of mast cells with amlexanox reduced the effect of the combination of amlexanox and isoproterenol, indicating tachyphylaxis; pretreatment with IBMX had no such effect. The cAMP content of macrophages was also increased by amlexanox, but when this compd. was combined with isoproterenol or PGE2, the effect was additive. Amlexanox inhibited cAMP phosphodiesterase [9036-21-9] in rat mast cells. These results suggest that amlexanox inhibits histamine release by augmenting the cAMP content in mast cells, and that this augmentation is caused by enhancing the cAMP generation and, additively, by inhibiting cAMP phosphodiesterase. .