Flurbinitroxybutylester: A novel anti-inflammatory drug has enhanced antithrombotic activity

We have recently shown that the introduction of a nitroxybutylester moiety into flurbiprofen, to form Flurbi-NO, results in a compound with markedly reduced undesired effects in the gastrointestinal tract. This effect has been shown to be linked to nitric oxide release from the Flurbi-NO. Here we ha...

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Bibliographic Details
Published in:Thrombosis research 1995-07, Vol.79 (1), p.73-81
Main Authors: Cirino, Giuseppe, Cicala, Carla, Mancuso, Franca, Baydoun, Anwar R., Wallace, John L.
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
Anti-Inflammatory Agents, Non-Steroidal - therapeutic use
Biological and medical sciences
Bones, joints and connective tissue. Antiinflammatory agents
Collagen - toxicity
Cyclooxygenase
Drug Evaluation, Preclinical
Epinephrine - toxicity
Fibrinolytic Agents - pharmacology
Fibrinolytic Agents - therapeutic use
Flurbiprofen - analogs & derivatives
Flurbiprofen - pharmacology
Flurbiprofen - therapeutic use
Humans
Male
Medical sciences
Mice
Molecular Structure
Nitric Oxide
Nitric Oxide - metabolism
NSAID
Pharmacology. Drug treatments
Platelet Aggregation - drug effects
Platelet Aggregation Inhibitors - pharmacology
Platelet Aggregation Inhibitors - therapeutic use
Rats
Rats, Wistar
Thromboembolism - chemically induced
Thromboembolism - drug therapy
thrombosis
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Summary:We have recently shown that the introduction of a nitroxybutylester moiety into flurbiprofen, to form Flurbi-NO, results in a compound with markedly reduced undesired effects in the gastrointestinal tract. This effect has been shown to be linked to nitric oxide release from the Flurbi-NO. Here we have investigated whether this is associated with a reduction in platelet aggregability in vivo, as assessed in a mouse model of thromboembolism and a rat model of platelet aggregation, and found in both models that Flurbi-NO is more potent than flurbiprofen at inhibiting collagen-induced platelet aggregation. Further in vitro studies using human washed platelets and cells in culture suggest that this is due to the release of NO from Flurbi-NO following the action of (possibly plasma) esterases. Together with our earlier data, these results strongly suggest that Flurbi-NO and other members of this class of drugs, have particular potential as antithrombotic agents devoid of gastrointestinal side effects.
ISSN:0049-3848
1879-2472
DOI:10.1016/0049-3848(95)00092-6