TY - JOUR
T1 - Flurbinitroxybutylester
T2 - a novel anti-inflammatory drug has enhanced antithrombotic activity
AU - Cirino, G.
AU - Cicala, C.
AU - Mancuso, F.
AU - Baydoun, A. R.
AU - Wallace, J. L.
N1 - Original article can be found at: http://www.sciencedirect.com/science/journal/00493848 Copyright Elsevier Ireland Ltd. DOI: 10.1016/0049-3848(95)00092-6 [Full text of this article is not available in the UHRA]
PY - 1995
Y1 - 1995
N2 - 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.
AB - 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.
U2 - 10.1016/0049-3848(95)00092-6
DO - 10.1016/0049-3848(95)00092-6
M3 - Article
SN - 0049-3848
VL - 79
SP - 73
EP - 81
JO - Thrombosis Research: Vascular Obstruction, Hemorrhage and Hemostasis
JF - Thrombosis Research: Vascular Obstruction, Hemorrhage and Hemostasis
ER -