Aphthasol
Inhibitory effect of HSR-6071, a new anti-allergic agent, on experimental asthma in rats and guinea-pigs.

Makino E, Ohashi T, Takahashi H, Kato H, Ito Y, Nagai H, Koda A, Azuma H.

Central Research Laboratories, Hokuriku Seiyaku Co. Ltd., Fukui, Japan.

The experimental asthma caused by IgE antibody in rats was inhibited by HSR-6071 (6-(1-pyrrolidinyl)-N-(1H-tetrazol-5-yl)-2-pyrazinecarboxamide) (0.01-0.1 mg kg-1 i.v.) in a dose-dependent manner. The inhibitory activity of HSR-6071 was more potent than those of disodium cromoglycate and ketotifen, and equipotent with amlexanox. The bronchoconstriction mediated by IgE or IgG antibody in guinea-pigs was also prevented by HSR-6071 (0.3, 1 and 3 mg kg-1 i.v.), amlexanox (3, 10 and 30 mg kg-1 i.v.) and ketotifen (0.1 mg kg-1 i.v.) but not by disodium cromoglycate (10 mg kg-1 i.v.). HSR-6071 was more potent than amlexanox, but less potent than ketotifen. HSR-6071 suppressed antigen-induced histamine and SRS-A release from minced lung tissues of guinea-pigs sensitized passively with rabbit anti-EA serum and was a more potent inhibitor of the release of SRS-A than of histamine. On the other hand, histamine- or acetylcholine-induced bronchoconstriction in guinea-pigs was scarcely affected by HSR-6071 at doses sufficient to inhibit the experimental asthma, but LTD4-induced bronchoconstriction was dramatically inhibited. These results indicate that the inhibitory action on experimental allergic asthma of HSR-6071 may be due to suppression of antigen-induced histamine and SRS-A release from lung tissues and to antagonism of SRS-A action. In addition, HSR-6071 inhibited cyclic AMP phosphodiesterase activity and produced relaxation of the guinea-pig isolated trachea. These pharmacological actions may contribute to the production of the anti-allergic action of HSR-6071.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1974289&dopt=Abstract amlexanox Aphthasol



Aphthasol
[Effect of amlexanox on experimental allergic rhinitis in actively sensitized guinea pigs]

[Article in Japanese]

Ukai K, Atsushi, Yuda, Nonoyama T, Sakakura Y, Ahida Y.

Department of Otorhinolaryngology, Mie University School of Medicine.

The effect of amlexanox given orally for 3 weeks was studied on the IgE-mediated experimental allergic rhinitis in the actively sensitized guinea pigs. The intranasal instillation of antigen (egg albumin) induced the increase of nasal vascular permeability (dye leakage), histamine content in nasal perfusate and nasal resistance in sensitized guinea pig. Amlexanox, 20 and 60 mg/kg/day given orally for 3 weeks significantly inhibited the increase of dye leakage into the nasal cavity, histamine content and nasal resistance in a dose-dependent manner. These results suggest that amlexanox given orally may be useful therapeutic agent for human allergic rhinitis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2350243&dopt=Abstract amlexanox Aphthasol



Aphthasol
[Changes in isolated ciliary muscle caused by repeated instillation of carbachol ointment in rabbits and effect of topically applied amlexanox]

[Article in Japanese]

Watanabe N, Ogawa T, Isaka M, Yorozuya T, Ushijima HT, Gomi Y.

Creative Center, Senju Pharmaceutical Co, Ltd, Osaka, Japan.

PURPOSE: We investigated changes in ciliary muscle caused by continual contraction in rabbits and evaluated the efficacy of topically applied amlexanox, which relaxes the ciliary muscle, on such changes. SUBJECTS AND METHODS: After topical application of carbachol ointment 5 times daily for 2 weeks, the contractile responses of isolated ciliary muscles to carbachol were measured isometrically, and the ciliary smooth muscle fibers were stained with phosphotungstic acid and hematoxylin and observed histologically. 1% amlexanox solution was instilled 5 minutes before every instillation of carbachol ointment. RESULTS: Repeated topical carbachol ointment caused decreases in both contractile responses of isolated ciliary muscles to carbachol and number of ciliary smooth muscle fibers stained by phosphotungstic acid and hematoxylin. Amlexanox inhibited these changes. CONCLUSION: We found that continual contraction of the ciliary muscle caused functional and histological changes in it. These changes are thought to occur in some diseases which cause excessive contraction of the ciliary muscle. Topical amlexanox might be useful for these diseases.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10659621&dopt=Abstract amlexanox Aphthasol