Pharmacologic actions of the second generation leukotriene B 4 receptor antagonist LY293111: in vivo pulmonary studies

Silbaugh, Steven A.; Stengel, Peter W.; Froelich, Larry L.; Bendele, Alison M.; Spaethe, Stephen M.; Sofia, Michael J.; Sawyer, J. Scott; Jackson, William T.

doi:10.1007/s002109900211

Cited by 26 publications

(15 citation statements)

References 43 publications

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“…BLT 1 -receptor antagonists, such as LY29311, have now been developed for the treatment of neutrophilic inflammation [193]. LY293111 and another antagonist SB225002 inhibit the neutrophil chemotactic activity of sputum from COPD patients, indicating the potential clinical value of such drugs [185,190] and several selective BLT 1 antagonists are now in development.…”

Section: Leukotriene B 4 Inhibitorsmentioning

confidence: 99%

COPD: current therapeutic interventions and future approaches

Barnes¹

2005

European Respiratory Journal

231

143

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Although long-acting bronchodilators have been an important advance for the management of chronic obstructive pulmonary disease (COPD), these drugs do not deal with the underlying inflammatory process. No currently available treatments reduce the progression of COPD or suppress the inflammation in small airways and lung parenchyma. Several new treatments that target the inflammatory process are now in clinical development. Some therapies, such as chemokine antagonists, are directed against the influx of inflammatory cells into the airways and lung parenchyma that occurs in COPD, whereas others target inflammatory cytokines such as tumour necrosis factor-a.Broad spectrum anti-inflammatory drugs are now in phase III development for COPD, and include phosphodiesterase-4 inhibitors. Other drugs that inhibit cell signalling include inhibitors of p38 mitogen-activated protein kinase, nuclear factor-kB and phosphoinositide-3 kinase-c. More specific approaches are to give antioxidants, inhibitors of inducible nitric oxide synthase and leukotriene B 4 antagonists. Other treatments have the potential to combat mucus hypersecretion, and there is also a search for serine proteinase and matrix metalloproteinase inhibitors to prevent lung destruction and the development of emphysema.More research is needed to understand the cellular and molecular mechanisms of chronic obstructive pulmonary disease and to develop biomarkers and monitoring techniques to aid the development of new therapies.

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Section: Leukotriene B 4 Inhibitorsmentioning

confidence: 99%

COPD: current therapeutic interventions and future approaches

Barnes¹

2005

European Respiratory Journal

231

143

View full text Add to dashboard Cite

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“…BLT 2 receptors are expressed on T lymphocytes (Yokomizo et al, 2000). BLT 1 antagonists, such as LY29311 (2-[2-propyl-3-[3-[2-ethyl-4-(4-fluorophenyl)-5-hydroxphenoxy]propoxy]phenoxy]benzoic acid), have now been developed for the treatment of neutrophilic inflammation (Silbaugh et al, 2000). BLT 1 -receptor antagonists inhibits the neutrophil chemotactic activity of sputum from COPD patients, indicating the potential clinical value of such drugs (Crooks et al, 2000;Beeh et al, 2003c), but they only give about 25% inhibition, indicating that other neutrophil chemotactic factors are also involved.…”

mentioning

confidence: 99%

Mediators of Chronic Obstructive Pulmonary Disease

2004

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“…Two subtypes of receptor for LTB 4 have been described; leukotriene B 4 receptor type 1(BLT 1 ) receptors are expressed mainly on granulocytes and monocytes, whereas B 4 receptor type 2 (BLT 2 ) receptors are expressed on Tlymphocytes [36]. BLT 1 antagonists, such as LY29311, have now been developed for the treatment of neutrophilic inflammation [37]. LY293111 and another antagonist, SB225002, inhibit the neutrophil chemotactic activity of sputum from COPD patients, indicating the potential clinical value of such drugs [38,39].…”

Section: Nitric Oxide Synthase Inhibitorsmentioning

confidence: 99%

New approaches to COPD

Barnes¹

2005

European Respiratory Review

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No currently available treatments reduce the progression or suppress the inflammation of chronic obstructive pulmonary disease (COPD). However, with a better understanding of the inflammatory and destructive process, several targets have been identified, and new treatments are now in clinical development.Several specific therapies are directed against the influx of inflammatory cells into the airways and lung parenchyma that occurs in COPD, including adhesion molecule and chemokine-directed therapy, as well as therapies to inhibit tumour necrosis factor-a. Broad spectrum antiinflammatory drugs are also in development, and include inhibitors of phosphodiesterase-4, p38 mitogen-activated protein kinase, nuclear factor-kB and phosphoinositide-3 kinase-c. More specific approaches include antioxidants, inhibitors of inducible nitric oxide synthase, and leukotriene B 4 receptor antagonists. Inhibitors of epidermal growth factor receptor kinase and calcium-activated chloride channel inhibitors have the potential to inhibit mucus hypersecretion. Other therapies are targeted at the structural changes of COPD. Therapy to inhibit fibrosis is being developed against transforming growth factor-b 1 and protease activated receptor-2. There is also a search for serine proteinase and matrix metalloproteinase inhibitors to prevent lung destruction and the development of emphysema, as well as drugs such as retinoids that may even reverse this process.There is the need for validated biomarkers and monitoring techniques in early clinical studies with new therapies for chronic obstructive pulmonary disease.

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Pharmacologic actions of the second generation leukotriene B 4 receptor antagonist LY293111: in vivo pulmonary studies

Cited by 26 publications

References 43 publications

COPD: current therapeutic interventions and future approaches

COPD: current therapeutic interventions and future approaches

Mediators of Chronic Obstructive Pulmonary Disease

New approaches to COPD

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