Shinji Takai*, Denan Jin, Masato Sakaguchi, Kazuyoshi Kirimura and Mizuo Miyazaki
Department of Pharmacology, Osaka Medical College, Takatsuki City, Osaka 569-8686, Japan
*Corresponding author. FAX: +81-726-84-6518, E-mail: pha010@art.osaka-med.ac.jp
Abstract: We investigated the effects of a novel chymase inhibitor, BCEAB (4-[1-{[bis-(4-methyl-phenyl)- methyl]-carbamoyl}-3-(2-ethoxy-benzyl)-4-oxo-azetidine-2-yloxy]-benzoic acid). The IC50 value of BCEAB for purified human chymase was 5.4 nM, whereas BCEAB did not inhibit the angiotensin-converting enzyme, elastase and tryptase. In isolated dog arteries, the IC50 value of BCEAB for the angiotensin I-induced contraction in the presence of 1 mM lisinopril was 2.8 mM. In the hamster, the heart chymase activities were significantly suppressed to 42.0% and 26.9% 3 h after oral administration of 100 and 300 mg of BCEAB/kg of body weight, respectively. In conclusion, BCEAB is a useful chymase inhibitor for studying the role of chymase in vivo.
Keywords: Chymase, Inhibitor, Oral administration
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