[Inhibitory effect of amlexanox (AA-673) on the immunological and non-immunological release of histamine or leukotrienes].
The effect of amlexanox on the non-immunological or immunological release of histamine or leukotrienes (LTs) from passively sensitized human lung fragments and atopic human leukocytes was investigated and compared with those of AA-861, tranilast, azelastine and disodium cromoglycate. 1) Amlexanox at concentrations of 10(-7)-10(-4) M showed an inhibition of histamine, LTB4, LTC4, LTD4 and LTE4 release from passively sensitized human lung fragments in a concentration-dependent fashion. A selective and competitive inhibitor of the 5-lipoxygenase activity, AA-861 modestly affected the histamine release and potently suppressed the any LT release at 10(-7) and 10(-6) M. Antiallergic drugs, tranilast and disodium cromoglycate also suppressed these chemical mediator release, but the inhibition potency was somewhat weaker than that of amlexanox. 2) Ca ionophore A23187-induced release of LTB4 and LTC4 from atopic human leukocytes was slightly enhanced up to 10(-6) M of amlexanox. However, 10(-4) M of the drug strongly diminished both of LT release. From these results, it is suggested that amlexanox is a clinically effective drug for atopic diseases, especially allergic asthma and rhinitis.
Kohno
S
S
Shimizu
T
T
Mizuta
J
J
Ogino
K
K
Yamamura
H
H
Ohata
K
K
Kawai
M
M
Shindo
T
T
Wada
H
H
Hitomi
S
S
D000631:Aminopyridines / Q000494:pharmacology*; D016227:Benzoquinones; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology; D066298:In Vitro Techniques; D007962:Leukocytes / Q000276:immunology* / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism*; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D011809:Quinones / Q000494:pharmacology; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D000631:Aminopyridines; D016227:Benzoquinones; D015289:Leukotrienes; D011809:Quinones; D062367:ortho-Aminobenzoates; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; C045742:amlexanox; C012293:tranilast