The anti-platelet actions of FR122047, a novel cyclooxygenase inhibitor

Dohi, Miwako; Sakata, Yoshihiko; Seki, Jiro; Namikawa, Yasuko; Fujisaki, Jiro; Tanaka, Akito; Takasugi, Hisashi; Motoyama, Yukio; Yoshida, Keizo

doi:10.1016/0014-2999(93)90378-u

Cited by 18 publications

(12 citation statements)

References 19 publications

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“…19 and 20). This panel of COX inhibitors consisted of ASA, a relatively non-specific COX inhibitor, though with greater activity toward the COX-1 isoform, 21 DuP-697 (5-bromo-2-(4-fluorophenyl-3-(4-methylsufonyl) phenylthiophene), a predominantly COX-2 inhibitor, 22 FR 122047 (1-[[4,5-bis(4-methoxyphenyl)-2-thiazolyl]carbonyl]-4-methyl-piperazine, monohydrochloride hydrate), a selective COX-1 inhibitor 23 and INDO (1-(chlorobenzoyl)-5-methoxy-2-methyl-3-indoleacetic acid), 24 a rather non-specific inhibitor, though with greater activity against COX-1. For a positive control of enhancement of 1,25D-induced differentiation we used SB202190, an inhibitor of p38MAP kinase with a known ability to increase the JNK pathway activity in myeloid leukemia cells.…”

Section: Resultsmentioning

confidence: 99%

Induction of differentiation of human leukemia cells by combinations of COX inhibitors and 1, 25-dihydroxyvitamin D3 involves Raf1 but not Erk 1/2 signaling

Jamshidi

Zhang²,

Harrison³

et al. 2008

Cell Cycle

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Section: Resultsmentioning

confidence: 99%

Induction of differentiation of human leukemia cells by combinations of COX inhibitors and 1, 25-dihydroxyvitamin D3 involves Raf1 but not Erk 1/2 signaling

Jamshidi

Zhang²,

Harrison³

et al. 2008

Cell Cycle

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“…Samples were treated 1 min prior to collagen with 10 ml of saline (control) or concentrations of either GSNO or RIG200 to give ®nal drug concentrations in cuvettes of 0.3 ± 100 mM and an IC 50 concentration of aspirin (10 mM), as determined by pilot experiments (n=3). The concentration used is slightly lower than that reported previously for aspirin in vitro (*45 mM; Dohi et al, 1993), perhaps because of dierences in the population from which blood was derived. Aspirin experiments were used to determine whether RBCs could in¯uence NO-independent inhibition of platelet aggregation.…”

mentioning

confidence: 83%

Inhibition of human platelet aggregation by a novel S‐nitrosothiol is abolished by haemoglobin and red blood cells in vitro: implications for anti‐thrombotic therapy

Megson

Sogo

Mazzei

et al. 2000

British J Pharmacology

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1 S-Nitrosothiols are nitric oxide (NO) donor drugs that have been shown to inhibit platelet aggregation in platelet rich plasma (PRP) in vitro and to inhibit platelet activation in vivo. The aim of this study was to compare the platelet eects of a novel S-nitrosated glyco-amino acid, RIG200, with an established S-nitrosothiol, S-nitrosoglutathione (GSNO) in PRP, and to investigate the eects of cell-free haemoglobin and red blood cells on S-nitrosothiol-mediated inhibition of platelet aggregation. 2 The eects of GSNO and RIG200 in collagen (2.5 mg ml 71 )-induced platelet aggregation in PRP and whole blood were investigated in vitro. Both compounds were found to be powerful inhibitors of aggregation in PRP, and RIG200 was signi®cantly more potent (IC 50 =2.0 mM for GSNO and 0.8 mM for RIG200; P=0.04). 3 Neither compound inhibited aggregation in whole blood, even at concentrations of 100 mM. Red blood cell concentrations as low as 1% of the haematocrit, and cell-free haemoglobin (52.5 mM), signi®cantly reduced their inhibitory eects on platelets. 4 Experiments involving measurement of cyclic GMP levels, electrochemical detection of NO and electron paramagnetic resonance of haemoglobin in red blood cells, indicated that scavenging of NO generated from S-nitrosothiols by haemoglobin was responsible for the lack of eect of Snitrosothiols on platelets in whole blood. 5 These studies suggest that scavenging of NO by haemoglobin in blood might limit the therapeutic application of S-nitrosothiols as anti-platelet agents.

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“…This might result in increased myocardial oxygen supply during the reperfusion period, thus decreasing the resulting myocardial infarct size. Moreover, the preponderance of prostaglandins might reduce platelet aggregation, 35 helping to prevent coronary microemboli during reperfusion. Nevertheless, these various effects could have been actuated by any available COX inhibitor due to different affinities and variety of mechanisms.…”

Section: Discussionmentioning

confidence: 99%

The Role of Cyclooxygenase-1 and -2 in Sevoflurane-Induced Postconditioning Against Myocardial Infarction

Stumpner

Tischer-Zeitz

Frank

et al. 2014

Semin Cardiothorac Vasc Anesth

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Cyclooxygenase (COX)-2 mediates ischemic pre-and postconditioning as well as anesthetic-induced preconditioning. However, the role of COX-1 and -2 in anesthetic-induced postconditioning has not been investigated. We evaluated the role of COX-1 and -2 in sevoflurane-induced postconditioning in vivo. Pentobarbital-anaesthetized male C57BL/6 mice were subjected to 45 minutes of coronary artery occlusion and 3 hours of reperfusion. Animals received either no intervention, the vehicle dimethyl sulfoxide (DMSO, 10 µL/g intraperitoneally), acetylsalicylic acid (ASA, 5 µg/g intraperitoneally), the selective COX-1 inhibitor SC-560 (10 µg/g intraperitoneally), or the selective COX-2 inhibitor NS-398 (5 µg/g intraperitoneally). 1.0 MAC (minimum alveolar concentration) sevoflurane was administered for 18 minutes during early reperfusion either alone or in combination with ASA, SC-560, and NS-398. Infarct size was determined with triphenyltetrazolium chloride. Statistical analysis was performed using 1-way and 2-way analyses of variance with post hoc Duncan testing. The infarct size in the control group was 44% ± 9%. DMSO (42% ± 7%), ASA (36% ± 6%), and NS-398 (44% ± 18%) had no effect on infarct size. Sevoflurane (17% ± 4%; P < .05) and SC-560 (26% ± 10%; P < .05) significantly reduced the infarct size compared with control condition. Sevoflurane-induced postconditioning was not abolished by ASA (16% ± 5%) and SC-560 (22% ± 4%). NS-398 abolished sevoflurane-induced postconditioning (33% ± 14%). It was concluded that sevoflurane induces postconditioning in mice. Inhibition of COX-1 elicits a myocardial infarct size reduction and does not abolish sevoflurane-induced postconditioning. Blockade of COX-2 abolishes sevofluraneinduced postconditioning. These results indicate that sevoflurane-induced postconditioning is mediated by COX-2.

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The anti-platelet actions of FR122047, a novel cyclooxygenase inhibitor

Cited by 18 publications

References 19 publications

Induction of differentiation of human leukemia cells by combinations of COX inhibitors and 1, 25-dihydroxyvitamin D3 involves Raf1 but not Erk 1/2 signaling

Induction of differentiation of human leukemia cells by combinations of COX inhibitors and 1, 25-dihydroxyvitamin D3 involves Raf1 but not Erk 1/2 signaling

Inhibition of human platelet aggregation by a novel S‐nitrosothiol is abolished by haemoglobin and red blood cells in vitro: implications for anti‐thrombotic therapy

The Role of Cyclooxygenase-1 and -2 in Sevoflurane-Induced Postconditioning Against Myocardial Infarction

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