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Thieno-triazolo-1,4-diazepines as antagonists of platelet-activating factor: Present status

  • PAF Receptor and Antagonists
  • Review
  • Published:
Lipids

Abstract

The platelet-activating factor, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, (PAF) antagonistic activity of thienotriazolodiazepines has recently been described. The lead compound in this series was brotizolam, which also exhibits sedative and hypnotic effects. By combination of brotizolam with the benzodiazepine receptor antagonist RO 15-1788, PAF antagonistic and central nervous system (CNS) activities could be segregated. Systematic structure variation has led to potent and selective PAF antagonists without CNS effects. WEB 2086 and its analogues WEB 2170 and STY 2108 are representative examples of this structural type and have shown a high potency and selectivity in PAF-induced and PAF-dependentin vitro tests and in experimental models. Studies in healthy volunteers have demonstrated potent pharmacological activity and good safety and tolerance of oral, intravenous or inhaled WEB 2086 in man. These agents should therefore prove useful for the further elucidation of the pathophysiological role of PAF and provide an opportunity for therapeutic applications in diseases in which the involvement of PAF has been implicated.

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Abbreviations

ADP:

adenosine diphosphate

BDZ:

benzodiazepine

CNS:

central nervous system

ConA:

concanavalin A

FMLP:

N-formyl-L-methionyl-L-leucyl-L-phenylalanine

IC50 :

inhibitory concentration 50%

LD50 :

lethal dose 50%

LTB4 :

leukotriene B4

PAF:

platelet-activating factor, 1-o-alkyl-2-acetyl-sn-glycero-3-phosphocholine

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Authors and Affiliations

  1. Boehringer Ingelheim KG, 6507, Ingelheim am Rhein, Germany

    Jorge Casals-Stenzel

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  1. Jorge Casals-Stenzel
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Casals-Stenzel, J. Thieno-triazolo-1,4-diazepines as antagonists of platelet-activating factor: Present status. Lipids 26, 1157–1161 (1991). https://doi.org/10.1007/BF02536522

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  • DOI: https://doi.org/10.1007/BF02536522

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