Disease relevance of Trapymin

• The estimated rate of overall stenoses (intention-to-treat analysis) at 1 year showed a significant reduction in patients receiving trapidil and ticlopidine (group 2) as compared with heparin (33 vs. 57%; P =.047) [1].
• CONCLUSION: Oral trapidil 600 mg daily for 6 months did not reduce in-stent hyperplasia or improve clinical outcome after successful Wallstent implantation and is not indicated for this purpose [2].
• Triazolopyrimidine (trapidil), a platelet-derived growth factor antagonist, inhibits parathyroid bone disease in an animal model for chronic hyperparathyroidism [3].
• However, dramatic reductions in marrow fibrosis and bone resorption, but not bone formation, were observed in PTH-treated rats given trapidil [3].
• Matrix metalloproteinase 2 is suppressed by trapidil, a CD40-CD40 ligand pathway inhibitor, in human abdominal aortic aneurysm wall [4].

High impact information on Trapymin

• Similar down-regulation of the blood cell recruitment responses to DSS was noted in WT mice treated with the CD40-CD40L pathway inhibitor Trapidil [5].
• METHODS AND RESULTS: The Studio Trapidil versus Aspirin nella Restenosi Coronarica (STARC) is a multicentric, randomized, double-blind trial to assess the effects of trapidil in angiographic restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA) [6].
• In this study, trapidil significantly increased the luminal area and reduced the intimal thickness in the atherosclerotic rabbit iliac artery after balloon angioplasty [7].
• Platelet aggregation and platelet-derived growth factor inhibition for prevention of insufficiency of the transjugular intrahepatic portosystemic shunt: a randomized study comparing trapidil plus ticlopidine with heparin treatment [1].
• Trapidil administration suppressed Src and PDGFR-beta activation in the reperfused kidney and resulted in deteriorated renal function [8].

Chemical compound and disease context of Trapymin

• Prevention of cerebral ischemic symptoms in cerebral vasospasm with trapidil, an antagonist and selective synthesis inhibitor of thromboxane A2 [9].
• These findings suggest that trapidil interrupts the autocrine loop at the PDGF and PDGF-receptor level and that combination therapy with trapidil and ACNU may be useful in the treatment of glioma [10].
• Treatment of premature sonographic placental maturity with 50 mg acetylsalicylic acid (ASA) per day and three times daily 100 mg Rocornal, respectively, resulted in a significant increase of the birth weights [11].
• Propranolol, a beta-blocker, did not modify the initial peak but attenuated markedly the second peak (P less than 0.05) in case of trapidil (1.0 mg/kg i.v.) or nitroglycerin (10 micrograms/kg i.v.), which corresponded with reduced changes in reflex tachycardia and positive inotropism [12].
• These results indicate that acceleration of PGI2 generation from aorta by trapidil is involved in the mode of action of this drug of thrombus formation [13].

Biological context of Trapymin

• Trapidil also induced the phosphorylation of vasodilator-stimulated phosphoprotein in SMC [14].
• This study was designed to investigate the inhibition of mitogenesis by trapidil in cultured bovine coronary artery smooth muscle cells (SMC) and to identify major signal transduction pathways involved [14].
• The addition of 100 to 400 micrograms/ml Trapidil significantly reduced cell proliferation induced by different growth factors (FCS, PDGF-BB, bFGF, EGF), the highest inhibitory effect being on PDGF-BB stimulated MC growth [15].
• At low concentrations (1 X 10(-4) - 1 X 10(-3) M), trapidil induced slow action potentials accompanied by contractions, even in the presence of a beta-adrenergic blocker [16].
• Pharmacokinetics of trapidil in patients with chronic liver disease [17].

Anatomical context of Trapymin

• Antimitogenic effects of trapidil in coronary artery smooth muscle cells by direct activation of protein kinase A [14].
• Comparable inhibitory effects were obtained after stimulation of smooth muscle cells by phorbol ester, which suggests that the action of trapidil was not restricted to PDGF receptor-mediated mechanisms [14].
• The present results demonstrate that trapidil antagonizes PDGF-induced mitogenesis and MAP kinase activation in vascular smooth muscle cells, probably through cAMP [18].
• Trapidil inhibits human mesangial cell proliferation: effect on PDGF beta-receptor binding and expression [15].
• Trapidil inhibits monocyte chemoattractant protein-1 and macrophage accumulation after balloon arterial injury in rabbits [19].

Associations of Trapymin with other chemical compounds

• At the 4-week restudy, there was a significant preservation of luminal diameter in the trapidil group compared with the control group (1.27 +/- 0.20 vs. 0.94 +/- 0.48 mm, respectively; p less than 0.005) [7].
• Intravenous administration of Trapidil, as well as nitroglycerin, produced transient decreases in total coronary resistance followed by sustained dilation of the large coronary artery [20].
• This study was designed (i) to determine if local administration of trapidil (triazolopyrimidine) into a vessel wall reduces neointima formation, and (ii) to explore the mechanism involved in the subsequent reduction in cell proliferation [21].
• In contrast, at high concentrations (3 X 10(-3) - 1 X 10(-2) M), trapidil markedly depressed or blocked the isoproterenol-induced slow action potentials [16].
• At 5 X 10(-3) M, trapidil completely blocked the fast Na+ channels in hearts perfused with normal Tyrode solution, since this dose abolished the action potential when verapamil (2 X 10(-6) M) was present to eliminate the inward slow current [16].

Gene context of Trapymin

• Trapidil did not alter CD154 expression on isolated T cells, but it diminished CD40 expression on isolated monocytes and human monocytic leukemia THP-1 cells stimulated with interferon-gamma [22].
• RESULTS: Trapidil decreased thrombin-induced mRNA levels for bFGF and appeared to decrease mRNA for PDGF-A chain, but not for tPA [23].
• The subsequent studies on these two potential STAT1 phosphorylation sites (Tyr701, Ser727) revealed that Trapidil attenuated IFN-gamma-induced Ser727 but not Tyr701 phosphorylation [24].
• CONCLUSIONS: Trapidil, a CD40-CD40L pathway inhibitor, suppressed mRNA expression and protein production of MMP-2 in AAA tissues, suggesting a potential therapeutic approach for the prevention or treatment of AAA [4].
• CD40 was expressed on macrophages but not on neutrophils, and this expression could explain the differential effect of trapidil on the production of MMP-2 and MMP-9 [4].

Analytical, diagnostic and therapeutic context of Trapymin

• Trapidil in preventing restenosis after balloon angioplasty in the atherosclerotic rabbit [7].
• CONCLUSIONS: Trapidil reduces restenosis after PTCA at the dosage of 100 mg TID and favorably influences the clinical outcome thereafter [6].
• Intimal thickness was significantly less for the trapidil group than for the control group (0.33 +/- 0.15 vs. 0.44 +/- 0.15 mm, respectively; p = 0.01), as well as medial thickness (0.09 +/- 0.03 vs. 0.11 +/- 0.03 mm, respectively; p = 0.01) [7].
• Patients received either trapidil 100 mg TID or aspirin at the same dosage at least 3 days before angioplasty and for 6 months thereafter [6].
• RESULTS: Of 312 patients randomized at 21 centres in nine countries, 303 (148 trapidil, 155 placebo) underwent successful Wallstent implantation, and 139 patients (90%) in the placebo group and 130 (88%) in the trapidil group had repeat catheterization at 26+/-2 weeks [2].

References