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, Volume 38, Issue 1–2, pp 188–195 | Cite as

In vitro pharmacology of BAY X1005, a new inhibitor of leukotriene synthesis

  • R. Fruchtmann
  • K. -H. Mohrs
  • A. Hatzelmann
  • S. Raddatz
  • B. Fugmann
  • B. Junge
  • H. Horstmann
  • R. Müller-Peddinghaus
Allergy and Histamine

Abstract

BAY X1005, (R)-2-[4-(quinolin-2-yl-methoxy)phenyl]-2-cyclopentyl acetic acid, is an enantioselective inhibitor of leukotriene biosynthesis. It effectively inhibits the synthesis of LTB4 in A23187-stimulated leukocytes from rats, mice and humans (IC50 0.026, 0.039 and 0.22 μmol/l, respectively) as well as the formation of LTC4 (IC50 0.021 μmol/l) in mouse peritoneal macrophages stimulated with opsonized zymosan. The compound is, however, less active in inhibiting LTB4 synthesis in human whole blood (IC50 17.0 and 11.6 μmol/l, as measured by RIA or HPLC, respectively). BAY X1005 exhibits a high enantioselectivity in human whole blood (31 times over the (S)-enantiomer). BAY X1005 is shown to be a selective inhibitor of the formation of 5-lipoxygenase-derived metabolitesin vitro, without effects on other routes of arachidonic acid metabolism such as 12-lipoxygenase in human whole blood and cyclooxygenase in both mouse macrophages and human whole blood. BAY X1005 is devoid of any antioxidant activity (methemoglobin induction and xanthine-xanthine oxidase assay), without effects on granule release and with only weak effects on reactive oxygen species generation in human PMNL.

Keywords

Arachidonic Acid Reactive Oxygen Species Generation Peritoneal Macrophage LTB4 Arachidonic Acid Metabolism 

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Copyright information

© Birkhäuser Verlag 1993

Authors and Affiliations

  • R. Fruchtmann
    • 1
  • K. -H. Mohrs
    • 1
  • A. Hatzelmann
    • 2
  • S. Raddatz
    • 1
  • B. Fugmann
    • 1
  • B. Junge
    • 1
  • H. Horstmann
    • 2
  • R. Müller-Peddinghaus
    • 1
  1. 1.Pharmaceutical Research CenterBayer AGWuppertalFRG
  2. 2.TroponwerkeCologneFRG

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