Inhibition of Platelet Aggregation by a New Agent, Ticlopidine

Ashida, Shinji; Abiko, Yasushi

doi:10.1055/s-0038-1648687

Cited by 76 publications

(44 citation statements)

References 3 publications

(3 reference statements)

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“…These doses of ticlopidine and aspirin have been shown to inhibit platelet aggregation and thrombus formation in the rat (18)(19)(20)(21)(22)(23). Aspirin's inhibitory effects on thromboxane (TX) synthesis were confirmed by taking blood before sacrifice, allowing it to clot at 37°C for 45 min, and then measuring TXB 2 levels by ELISA (20).…”

Section: Methodsmentioning

confidence: 99%

Platelets modulate gastric ulcer healing: Role of endostatin and vascular endothelial growth factor release

Elliott

Cirino

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

225

193

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Bleeding and delayed healing of ulcers are well recognized clinical problems associated with the use of aspirin and other nonsteroidal antiinflammatory drugs, which have been attributed to their antiaggregatory effects on platelets. We hypothesized that antiplatelet drugs might interfere with gastric ulcer healing by suppressing the release of growth factors, such as vascular endothelial growth factor (VEGF), from platelets. Gastric ulcers were induced in rats by serosal application of acetic acid. Daily oral treatment with vehicle, aspirin, or ticlopidine (an ADP receptor antagonist) was started 3 days later and continued for 1 week. Ulcer induction resulted in a significant increase in serum levels of VEGF and a significant decrease in serum levels of endostatin (an antiangiogenic factor). Although both aspirin and ticlopidine markedly suppressed platelet aggregation, only ticlopidine impaired gastric ulcer healing and angiogenesis as well as reversing the ulcerassociated changes in serum levels of VEGF and endostatin. The effects of ticlopidine on ulcer healing and angiogenesis were mimicked by immunodepletion of circulating platelets, and ticlopidine did not influence ulcer healing when given to thrombocytopenic rats. Incubation of human umbilical vein endothelial cells with serum from ticlopidine-treated rats significantly reduced proliferation and increased apoptosis, effects reversed by an antibody directed against endostatin. Ticlopidine treatment resulted in increased platelet endostatin content and release. These results demonstrate a previously unrecognized contribution of platelets to the regulation of gastric ulcer healing. Such effects likely are mediated through the release from platelets of endostatin and possibly VEGF. As shown with ticlopidine, drugs that influence gastric ulcer healing may do so in part through altering the ability of platelets to release growth factors.angiogenesis ͉ ticlopidine ͉ aspirin ͉ proliferation ͉ endothelium

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Section: Methodsmentioning

confidence: 99%

Platelets modulate gastric ulcer healing: Role of endostatin and vascular endothelial growth factor release

Elliott

Cirino

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

225

193

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“…This results in elevation of cAMP in platelets, which again inhibits their aggregation. 25,26) Thus from the viewpoint of their end effects, ticlopidine and cilostazol have the same action. By avoiding platelet aggregation at the PTCA site, migration and proliferation of smooth muscle cells are suppressed and neointimal hyperplasia is obstructed.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Ticlopidine and Cilostazol for the Prevention of Restenosis after Percutaneous Transluminal Coronary Angioplasty.

et al. 2001

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SUMMARYPrevention of restenosis after percutaneous transluminal coronary angioplasty (PTCA) continues to be a significant problem. Recent controlled studies have demonstrated that cilostazol suppresses restenosis after PTCA. The effects of ticlopidine, another antiplatelet agent, were compared in terms of outcomes of patients randomized for treatment with the two drugs after PTCA. A total of 35 patients (47 lesions) were assigned prospectively and randomly to ticlopidine (17 patients, 24 lesions) and cilostazol (18 patients, 23 lesions) groups. Minimal luminal diameter (MLD) and percentage of stenosis to reference diameter were estimated before PTCA, just after the procedure and after 4 months follow-up. All patients underwent 4 months angiographic follow-up, at the end of which MLD was 2.03 ± 0.71 mm in the ticlopidine group and 2.05 ± 0.68 mm in the cilostazol group (p = 0.95), and the percentage of stenosis to reference diameter was 31.4 ± 16.7% and 30.0 ± 17.0%, respectively (p = 0.78). The restenosis rate was 12.5% in the ticlopidine group and 17.4% in the cilostazol group (p = 0.69), relatively low as compared to the 20% to 30% reported in previous studies. Adverse drug reactions during the followup period were observed in two of the ticlopidine group and none of the cilostazol group. We conclude that both ticlopidine and cilostazol are effective for the prevention of restenosis after PTCA, however the former may be associated with slight side effects. (Jpn Heart J 2001; 42: 43-54) Key words: Antiplatelet therapy, Follow-up studies, Quantitative coronary arteriography RESTENOSIS after percutaneous transluminal coronary angioplasty (PTCA) is still a major limitation to long-term successful therapy. Coronary stent implantation is associated with a significant reduction in the angiographic restenosis rate compared with conventional simple balloon angioplasty, with decreases to 20% to 30% reported by the BENESTENT 1) and STRESS 2) trials, but the search for

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“…1), is a potent and long acting inhibitor of platelet aggregation [1]. Platelets contribute significantly to arterial-occlusive thrombosis, one of the major causes of death and disease throughout the world.…”

Section: Introductionmentioning

confidence: 99%

Determination of ticlopidine in human plasma by capillary gas chromatography with ion trap detection

Pena

Lino

Silveira

2003

Journal of Pharmaceutical and Biomedical Analysis

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A gas chromatographic method for determination of ticlopidine in human plasma using mass spectrometric detection was developed. A Perkin Elmer model 8500 gas chromatograph coupled to an ion trap detector (ITD) in electron impact mode (EI) was used. The gas chromatograph was fitted with a 30 m )/0.32 mm i.d., DB-17 capillary column with a film thickness of 0.25 mm. The compounds were isolated from plasma by Extrelut-1 solid-phase extraction using hexane as the solvent of elution. The detection and quantification limits for this method were 0.005 and 0.01 mg/ml, respectively. The calibration curves were linear from 0.01 and 2.5 mg/ml. Recoveries from human plasma spiked at 0.01 and 2.0 mg/ml ranged from 84.4 and 87.3%. The coefficient of variation (CV) was between 5.1 and 6.9%. The results show that the sensitivity, accuracy and precision of the method are adequate for the determination of ticlopidine in human plasma samples. The ITD in SIM mode allows the unequivocal identification of ticlopidine. The suitability of this method was evaluated in the determination of ticlopidine in plasma from healthy volunteers following oral administration of a dose of 500 mg/day. #

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Inhibition of Platelet Aggregation by a New Agent, Ticlopidine

Cited by 76 publications

References 3 publications

Platelets modulate gastric ulcer healing: Role of endostatin and vascular endothelial growth factor release

Platelets modulate gastric ulcer healing: Role of endostatin and vascular endothelial growth factor release

Comparison of Ticlopidine and Cilostazol for the Prevention of Restenosis after Percutaneous Transluminal Coronary Angioplasty.

Determination of ticlopidine in human plasma by capillary gas chromatography with ion trap detection

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