Aphthasol
Effect of NZ-107, a newly synthesized pyridazinone derivative, on antigen-induced contraction of human bronchial strips and histamine release from human lung fragments or leukocytes.

Nagai H, Suda H, Iwama T, Daikoku M, Yanagihara Y, Koda A.

Department of Pharmacology, Gifu Pharmaceutical University, Japan.

The effects of a newly synthesized pyridazinone derivative, NZ-107, 4-bromo-5-(3-ethoxy-4-methoxybenzylamino)-3(2H)-pyridazinone, and two well-known antiasthmatic drugs, amlexanox (orally active disodium cromoglycate-like drug) and disodium cromoglycate (DSCG) on antigen-, histamine- and leukotriene C4 (LTC4)-induced constriction of isolated human tracheal muscle, and histamine release from human lung tissues and leukocytes were investigated in vitro. In some experiments, salbutamol was used as a reference drug. NZ-107 inhibited antigen-, histamine- and LTC4-induced contraction of tracheal muscle. Amlexanox and DSCG did not affect the contractile response of tracheal muscle caused by each stimulant. Salbutamol inhibited antigen-induced contraction of tracheal muscle. NZ-107, amlexanox, DSCG and salbutamol clearly inhibited the antigen-induced release of histamine and LTC4 from human lung tissue. The antigen-induced histamine release from atopic human leukocytes was inhibited by NZ-107 and amlexanox, but not by DSCG. Pretreatment with IL-3 did not alter antigen-induced contraction of tracheal muscle and histamine release from lung tissue, but antigen- or calcium ionophore A 23187-induced histamine release from leukocytes was clearly enhanced. Amlexanox inhibited the IL-3-induced enhancement of histamine release from leukocytes in the case of both stimuli, but NZ-107 and DSCG had no effect. These data suggest that NZ-107 has potent anti-allergic actions based on the inhibition of antigen-induced contraction of human tracheal muscle and mediator release from human lung tissue and leukocytes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1378042&dopt=Abstract amlexanox Aphthasol



Aphthasol
[Inhibitory action amlexanox on interleukin-3-induced enhancement of histamine releasability of human leukocytes]

[Article in Japanese]

Urisu A, Iimi K, Kondo Y, Horiba F, Masuda S, Tsuruta M, Yazaki T, Torii S.

Department of Pediatrics, Fujita Health University School of Medicine.

Amlexanox, an anti-allergic drug, showed a concentration-dependent inhibition against hrIL-3-induced enhancement of in vitro histamine release from human leukocytes by anti-IgE. The significant inhibitory action of amlexanox was observed in one out of nine and six out of nine allergic subjects at concentrations of 10(-5) M and 10(-4) M, respectively. This means that the inhibitory effect of amlexanox varied from patient to patient. Post-treatment as well as simultaneous treatment with amlexanox produced an inhibitory action on the enhancing effect of hrIL-3, suggesting that hrIL-3-induced enhancement of releasability is a reversible reaction. AA-861, OKY-046, superoxide dismutase and prostaglandin E2 showed no effects on the hrIL-3-induced enhancement of histamine releasability. The inhibitory action of amlexamox to the hrIL-3-induced enhancement of histamine releasability may be a new anti-allergic mechanism, details of which remains unclear.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1701989&dopt=Abstract amlexanox Aphthasol



Aphthasol
Inhibitory effect of levocabastine on experimental allergic conjunctivitis in guinea pigs.

Kamei C, Izushi K, Tasaka K.

Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.

The effect of levocabastine on allergic and histamine (Hi)-induced conjunctivitis in guinea pigs was compared with those of cromolyn sodium and amlexanox. Levocabastine inhibited both antigen- and Hi-induced conjunctivitis. Amlexanox had no effect on Hi-induced conjunctivitis; however, the drug elicited a significant inhibition of allergic conjunctivitis. On the other hand, the effect of cromolyn sodium was almost negligible in both cases. Levocabastine moderately inhibited Hi release from guinea pig conjunctiva induced by antigen-antibody reactions. Amlexanox also caused a significant inhibitory effect, whereas cromolyn sodium was not effective in suppressing Hi release induced by antigen challenge. Furthermore, levocabastine prevented an increase in the vascular permeability elicited by both Hi and antigen instillation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1723098&dopt=Abstract amlexanox Aphthasol