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[Thromboxane A2 antagonist--discovery of seratrodast].
Yakugaku Zasshi. 1999 May; 119(5):377-90.YZ

Abstract

We were interested in RCS (rabbit aorta contracting substance) and SRS-A (slow reacting substance of anaphylaxis) and their involvement in human bronchial asthma. When we started our anti-asthmatic drug research in the 1970's. We synthesized a lot of chemical compounds and eventually discovered that AA-861 inhibited the generation of SRS-A from the lung tissue of actively sensitized guinea pigs. AA-861 was found to be a potent 5-lipoxygenase inhibitor. This compound reduced experimental allergic asthma in guinea pigs, but it is easily metabolized in the body. More recently, we found a novel compound, AA-2414 (seratrodast), which is not metabolized in the body. AA-2414 proved to be not a 5-lipoxygenase inhibitor, but a thromboxane A2 (TXA2) receptor antagonist. Seratrodast is the first receptor antagonist that is being developed as an anti-asthmatic drug. Seratrodast inhibits both immediate-, late asthmatic responses in guinea pigs, and also reduces airway hyperresponsiveness in dogs. The anti-asthmatic action of seratrodast in animal models indicates that the drug should be of use in the treatment of human asthmatics. In clinical studies, seratrodast showed a marked effect to improve clinical parameters in bronchial asthma. It is also reported that seratrodast is free from harmful aftereffects. Clinical trials are under way in the US.

Authors+Show Affiliations

Pharmaceutical Research Division, Takeda Chemical Industries, Osaka, Japan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

English Abstract
Journal Article
Review

Language

jpn

PubMed ID

10375998

Citation

Terao, S, et al. "[Thromboxane A2 Antagonist--discovery of Seratrodast]." Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan, vol. 119, no. 5, 1999, pp. 377-90.
Terao S, Shiraishi M, Matsumoto T, et al. [Thromboxane A2 antagonist--discovery of seratrodast]. Yakugaku Zasshi. 1999;119(5):377-90.
Terao, S., Shiraishi, M., Matsumoto, T., & Ashida, Y. (1999). [Thromboxane A2 antagonist--discovery of seratrodast]. Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan, 119(5), 377-90.
Terao S, et al. [Thromboxane A2 Antagonist--discovery of Seratrodast]. Yakugaku Zasshi. 1999;119(5):377-90. PubMed PMID: 10375998.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Thromboxane A2 antagonist--discovery of seratrodast]. AU - Terao,S, AU - Shiraishi,M, AU - Matsumoto,T, AU - Ashida,Y, PY - 1999/6/22/pubmed PY - 1999/6/22/medline PY - 1999/6/22/entrez SP - 377 EP - 90 JF - Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan JO - Yakugaku Zasshi VL - 119 IS - 5 N2 - We were interested in RCS (rabbit aorta contracting substance) and SRS-A (slow reacting substance of anaphylaxis) and their involvement in human bronchial asthma. When we started our anti-asthmatic drug research in the 1970's. We synthesized a lot of chemical compounds and eventually discovered that AA-861 inhibited the generation of SRS-A from the lung tissue of actively sensitized guinea pigs. AA-861 was found to be a potent 5-lipoxygenase inhibitor. This compound reduced experimental allergic asthma in guinea pigs, but it is easily metabolized in the body. More recently, we found a novel compound, AA-2414 (seratrodast), which is not metabolized in the body. AA-2414 proved to be not a 5-lipoxygenase inhibitor, but a thromboxane A2 (TXA2) receptor antagonist. Seratrodast is the first receptor antagonist that is being developed as an anti-asthmatic drug. Seratrodast inhibits both immediate-, late asthmatic responses in guinea pigs, and also reduces airway hyperresponsiveness in dogs. The anti-asthmatic action of seratrodast in animal models indicates that the drug should be of use in the treatment of human asthmatics. In clinical studies, seratrodast showed a marked effect to improve clinical parameters in bronchial asthma. It is also reported that seratrodast is free from harmful aftereffects. Clinical trials are under way in the US. SN - 0031-6903 UR - https://www.unboundmedicine.com/medline/citation/10375998/[Thromboxane_A2_antagonist__discovery_of_seratrodast]_ L2 - https://www.lens.org/lens/search?q=citation_id:10375998 DB - PRIME DP - Unbound Medicine ER -