Practica oto-rhino-laryngologica. Suppl.

MY-5116 is a newly synthesized antiallergic agent and the metabolite, of which MY-1250, inhibits the release of chemical mediators from mast cells in animals.
This paper describes the inhibitory effect of MY-1250 on the release of histamine and SRS-A from allergen-stimulated human basophils collected from patients with al- lergic rhinitis induced by the pollen of Cryptomeria Japonica D. Don (PCJ). Basophils purified from a donor's peripheral blood were passively sensitized with the same donor's reaginic serum containing anti-PCJIgE class antibodies (aPCJIgEAb).
1) Added before antigen stimulation, MY-1250 produced a dose dependent inhibition with an ED₅₀ 10^-8-10^-8g/ml of specific antigen (PCJ) induced histamine and SRS-A release from human peripheral basophils passively sensitized with aPCJ-IgEAb.
2) MY-1250 also inhibited Ca²⁺ ior. ophore A23187 induced histamine and SRS-A release from non passively sensitized human peripheral basophils in a dose dependent manner when added to these cells before A23187 stimulation.
3) It has been reported that the oral administration of 150 mg of MY-5116 in humans gives a maximum plasma MY-1250 level of 1.5×10^-8g/ml. Considering the in vitro efficacy of MY-1250 in this experiment and the reported human plasma. level, MY-5116 should be a useful prophylactic drug for various type I allergic diseases, including allergic rhinitis.

View full abstract

Show abstractHide abstract

This report describes the effect of MY-5116, a new preventive drug for type I allergic disease, on the degranulation of basophils and mast cells (metachromatic cells) in nasal fluids of patients with allergic rhinitis induced by house dust antigen in the author's new method of testing allergies. (Once absorbed through the gastro-intestinal tract, MY-5116 is immediately hydrolyzed MY-1250, which has a potent antiallergic effect in animals by inhibiting the release of chemical mediators from mast cells. In this experiment MY-1250 was used instead of MY-5116. )
1) Degranulation occurs when metachromatic cells are stimulated by a-IgE, but not by a-IgA, a-IgD, a-IgM, a-κ, or a-λ. These results suggest that degranulation occurs only when IgE antibodies in receptors on metachromatic cells are bridged with anti-IgE.
2) The specific antigen extracted from allergen by Yagura's method and compound 48/80 also induce degranulation of metachromatic cells in nasal smears. The optimal concentration of the specific antigen is 25μg/ml, and that of compound 48/80 is 0.05μg/ml.
3) When metachromatic cells from healthy subjects are stimulated with anti-IgE,6.8±5.2% of the cells show degranulation. However, when such cells from patients with allergic rhinitis are stimulated with anti-IgE,83.9±11.4% of cells show degranulation.
4) MY-1250 inhibits the specific antigen and compound 48/80 induced degranulation of metachromatic cells of patients with allergic rhinitis. MY-1250 inhibits the degranulation of metachromatic cells when it is added to the metachromatic cells before antigen-stimulation. These data suggest that MY-5116 is a new use- ful preventive and therapeutic drug for allergic rhinitis.

View full abstract

Download PDF (1586K)

Register with J-STAGE for free!