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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Muratani, E. Hamamura, I. Kishimoto, T. Mitsuhashi, H. Nonaka, T. Fujii, K. |
| Description | Author Affiliation: Mitsuhashi H ( Teijin Institute for Bio-Medical Research, Hino, Tokyo, Japan. h.mitsuhashi@teijin.co.jp) |
| Abstract | 1. TEI-8362, 4-(N-(3-((3-carboxypropyl)amino)-8-methyl-1-oxo-4-azaisochromen-6- yl)carbamoyl)-4-((phenylmethoxy)carbonylamino)butanoic acid (C26H28N4O9) is a novel inhibitor of human neutrophil elastase (HNE). We evaluated its pharmacological profile in vitro and in vivo. 2. TEI-8362 demonstrated potent inhibition of HNE with a Ki value of 1.38 x 10(-9) M. Its selectivity for HNE among a variety of proteases ranged from 163 fold to 68,000 fold in favour of HNE. 3. The pulmonary haemorrhage that occurred after i.t. instillation of HNE to hamsters was inhibited by either i.t., i.v., or inhalant administration of TEI-8362. 4. Intratracheal administration of lipopolysaccharide induced pulmonary neutrophilia. Twenty-four hours after lipopolysaccharide administration, the additional treatment with formyl-methionyl-leucyl-phenylalanine resulted in a specific neutrophil-dependent acute lung injury. In this model, lung injury was significantly attenuated by i.t., i.v., or inhalant administration of TEI-8362. 5. These pharmacological actions of TEI-8362 suggest that this drug has therapeutic value in the treatment of destructive lung diseases due to neutrophils. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 5 |
| Volume Number | 126 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1999-03-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Butyrates Carbamates Pharmacology Enzyme Inhibitors Leukocyte Elastase Antagonists & Inhibitors Animals Butyric Acid Cricetinae Therapeutic Use Lipopolysaccharides Mesocricetus N-Formylmethionine Leucyl-Phenylalanine Neutrophils Physiology Protective Agents Respiratory Distress Syndrome, Adult Chemically Induced Enzymology Prevention & Control Substrate Specificity |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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