Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Trapidil”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed1987

Inhibition of thromboxane B2 formation of blood platelets by trapidil and other s-triazolo(1,5-a)pyrimidine derivatives.

Trapidil and some other 5,7-disubstituted s-triazolo(1,5-a)pyrimidine derivatives (TPDs) which were shown to have potent actions against platelet aggregation also inhibited in vitro platelet thromboxane A2 (TXA2) biosynthesis in clotting human and rabbit whole blood as well as in arachidonic acid-activated platelet-rich human plasma. The inhibitory potency of TPDs on TXB2 formation paralleled the antiaggregatory effectiveness to a certain extent and decreased in the following order: AR 12456 greater than AR 12463 approximately AR 12464 approximately AR 12465 greater than trapidil. When TPDs were administered orally to rabbits and blood was taken 2 hours later, no changes of serum TXB2 level were observed. After i.v. injection of TPDs in rabbits, the most active TPDs AR 12456 and AR 12463 led to a short-lasting reduction of serum TXB2 by 61.4 and 49.4% resp.. The TXB2 levels returned nearly to pre-treatment level after 80 min. The possibility is discussed that TPDs mainly prevent platelet TXA2 formation by inhibiting phosphodiesterase activity.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMedDate not supplied

Trapidil derivatives and low density lipoprotein metabolism by human skin fibroblasts and by human hepatoma cell line Hep G2.

The effect of trapidil (RocornalR) and some of its newly developed derivatives (AR 12456, AR 12463, AR 12465, AR 12464) on the receptor-mediated low density lipoprotein (LDL) binding, uptake and degradation was studied in human skin fibroblasts (HSF) and in human hepatoma cell line Hep G2. Compound AR 12456 influenced this pathway in a selective way: it enhanced the uptake and degradation of 125I-LDL by Hep G2 cells in a dose-dependent manner, but inhibited it in HSF. Scatchard analysis of the saturable LDL binding in Hep G2 indicates that the effect of compound AR 12456 is the result of an increased number of LDL binding sites. Compound AR 12465 was less effective on LDL catabolism. Trapidil and the other derivatives were inactive under the same experimental conditions. When Ar 12456 was preincubated with Hep G2 cells and then the incubation medium was transferred to HSF, a stimulation of specific LDL pathway occurred also in this cell line. These findings suggest that a metabolite(s) of AR 12456 might be responsible for the enhanced expression of LDL receptors in cultured human cells.

Animals↗
PubMed1991

Influence of trapidil and derivatives on cholesterol synthesis and esterification in cultured cells.

The effect of trapidil (Rocornal) and its derivatives AR 12456 and AR 12463 on endogenous cholesterol synthesis and on cholesterol esterification rate was studied in human skin fibroblasts (HSF), in human hepatoma cell line Hep G2 and in primary culture of peritoneal macrophages from mouse (PMM). The cholesterol esterification rate was not influenced by the drugs in the tested cell lines. The incorporation of [14C]acetate into cholesterol in HSF was inhibited by AR 12463 and AR 12456, but not by trapidil. The inhibitory potency of AR 12456 in HSF was enhanced after preincubation of the drug with Hep G2 and removal of the medium to HSF, suggesting that the formed metabolite(s) are more potent inhibitors than the parent substance. The metabolite(s) formed seem(s) to influence the first steps in the endogenous formation of cholesterol, because the incorporation of [14C]mevalonate into cholesterol was not significantly inhibited. These findings suggest that the demonstrated inhibition of the endogenous cholesterol synthesis by AR 12456, especially after transformation into a probably more active substance(s), together with the recently described enhanced expression of LDL receptors in Hep G2 cells may partially explain the hypocholesterolaemic activity of AR 12456.

Acetates↗
PubMed1981

Prevention of cerebral ischemic symptoms in cerebral vasospasm with trapidil, an antagonist and selective synthesis inhibitor of thromboxane A2.

The results of our previous experimental and clinical studies led us to the hypothesis that, in the pathogenesis of cerebral vasospasm, subarachnoid focal acidosis resulting from anaerobic changes of subarachnoid clots may be a factor upsetting the balanced synthesis of both thromboxane A2 and prostaglandin I2 from prostaglandin endoperoxides on the inner surface of cerebral arteries. Thus, there is a higher concentration of thromboxane A2, a prostanoid that causes arterial contraction and platelet aggregation. We tested the administration of trapidil, an antagonist and selective synthesis inhibitor of thromboxane A2, in a series of 20 cases for the prevention of cerebral vasospasm and cerebral ischemia after aneurysmal rupture. Vasospasm was demonstrated by angiography in 9 of these cases, but only 2 of the 9 showed mild signs of cerebral ischemia. Of the 20 patients, 15 were discharged from the hospital as cured and 3 had a neurological deficit at discharge. Our findings suggest the significance in symptomatic vasospasm of thrombus formation by platelet aggregation and the effectiveness of trapidil as a preventive.

Adult↗
PubMed1994

The trapidil restenosis trial (STARC study): background, methods and clinical characteristics of the patient population.

Restenosis remains the principal drawback of percutaneous transluminal coronary angioplasty (PTCA) since 30-35% of patients still experience it 6 months after the intervention. Several studies have clearly demonstrated that restenosis is a complex multifactorial process that involves smooth muscle cell (SMC) migration and proliferation in the intimal layer of the coronary artery. Among others, the platelet-derived growth factor (PDGF) seems to play an important role in this process. That is why researches have been made in finding and developing new agents able to inhibit PDGF. Trapidil (triazolopyrimidine) (T), is a potent PDGF inhibitor that has been efficacious in preventing restenosis after balloon angioplasty in the experimental animal and after PTCA in a limited clinical trial. The Trapidil Restenosis Trial (STARC study) is a double blind randomized trial of T 100 mg t.i.d. vs. Aspirin (ASA) 100 mg t.i.d. 360 patients have been enrolled from April 1990 until May 1992, excluding recent myocardial infarctions, thrombolysis, restenotic and venous graft lesions and 302 have terminated follow-up. This paper describes the clinical background, the protocol and baseline data of the patient population including data regarding initial stenosis and type of vessel treated.

Adult↗
PubMedDate not supplied

Effect of trapidil in ischemia/reperfusion injury on rat small intestine.

To investigate the effect of trapidil on the intestinal ischemia-reperfusion injury, we determined malondialdehyde levels as a indicator of lipid peroxidation, nitrite and nitrate levels as reflections of nitric oxide metabolism, and histopathological findings in rats subjected to 40 min of ischemia and 2 h of reperfusion. Histopathological evaluation demonstrated that trapidil treatment has a protective effect on intestinal mucosa and reduces inflammatory cell infiltration in lamina propria, which is consistently noted in the untreated ischemic and reperfused intestines. Possible mechanism of this effect may be explained by the reduced lipid peroxidation (mean malondialdehyde level 3.72 +/- 0.27 vs. 6.13 +/- 0.44, p <.0001) and improved nitric oxide metabolism (mean nitrite plus nitrate 38.21 +/- 2.33 vs. 30.14 +/- 1.47, p =.022).

Animals↗
PubMed1991

[The effect of oral trapidil therapy on clinical and hemorheological parameters in arteriosclerosis obliterans in comparison to pentoxifylline--a pilot study].

20 male patients from 44 to 61 years of age with arteriosclerotic disturbances of the blood supply of the legs (stage II after Fontaine) were in the cross-over treated with 3 x 200 mg trapidil or 3 x 200 mg pentoxifylline daily. The duration of the therapy was in each case 6 weeks with a one-week elutriation phase. Statistically ascertained was an increase of the distance of intermittent claudication for the two drugs in patients with initial values lower than 550 m. On the other hand the tibio-brachial Doppler quotient and the submaximal blood supply established by the venous-occlusion plethysmography did not change. The post-ischaemic recovery phase of the transcutaneous oxygen partial pressure at the lower leg shortened in particular under the influence of trapidil. Lipid parameter, haematocrit, fibrinogen and plasma viscosity remained unchanged. The subjective tolerance of the two remedies was good.

Adult↗
PubMed1989

Bioavailability of trapidil tablets.

Trapidil was given orally (200 mg, Rocornal dragees 100 mg) and intravenously (100 mg) to 12 healthy volunteers. Serum samples were analyzed for trapidil by HPLC. Complete bioavailability was obtained and a mean absorption time of 66.4 min was calculated using the method of curve moments.

Administration, Oral↗
PubMed1987

Action of trapidil on the heart contractility: relationship to the cyclic nucleotide metabolism.

The relationship between the cardiotonic action of trapidil (RocornalR) and cyclic nucleotide metabolism was studied in the isolated rat heart. The contractility of the heart was increased in a concentration-dependent manner by this drug (ED50 20/microM). Parallel with the mechanical changes the tissue levels of cyclic AMP were increased, which was associated with an activation of the cAMP-dependent protein kinase. Cyclic GMP was enhanced only at a drug concentration of 1 mM. The present findings support the hypothesis that the cyclic nucleotide system is involved in the functional action of trapidil on cardiac tissue.

Animals↗
PubMed1988

Effect of derivatives of trapidil on the expression of LDL receptors.

The influence of trapidil and some of its derivatives (AR 12456, AR 12463, AR 12465) on the LDL receptor mediated uptake and degradation of 125 I-LDL by human skin fibroblasts (HSF) and human hepatic cells (HEP G2) was investigated. AR 12456 enhanced the uptake and degradation of 125 I-LDL in HEP G2, but inhibited this pathway in HSF. When this drug was preincubated with HEP G2 cells, and then the incubation medium was transferred to HSF, a stimulation of specific LDL pathway occurred also in this cell line. Trapidil, AR 12463 and AR 12465 were inactive under the same experimental conditions. These findings suggest that a metabolite of AR 12456 might be responsible for the enhanced expression of LDL receptors in human cells.

Antihypertensive Agents↗
PubMed1988

Inhibition of cytosolic Ca++ mobilization in human platelets by the antianginal drug trapidil and its derivative AR 12463.

The antianginal drug trapidil (5-methyl-7-diethylamino-s-triazolo-(1.5-a)pyrimidine) and its derivative AR 12463 (5-piperidino-7-(N-(n-amyl)-N-(beta-hydroxyethyl)-amino)-s-triazolo(1.5- a) pyrimidine) inhibit the thromboxane A2 agonist (U-46619)-induced mobilization of intracellular platelet-free Ca++ as measured with the fluorescent Ca++ indicator Indo-1. This inhibitory effect is independent of extracellular Ca++ concentration, and AR 12463 is about 70-fold more active than trapidil itself.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1987

Trial of platelet-derived growth factor antagonist, trapidil, in accelerated nephrotoxic nephritis in the rabbit.

The platelet-derived growth factor (PDGF) antagonist, trapidil, which also blocks the thromboxane and/or PG-endoperoxide receptor and is an inhibitor of thromboxane synthetase, was administered during rabbit accelerated nephrotoxic nephritis; the clinical and histological evolution was studied as well as urinary immunoreactive thromboxane (i-TXB2) and immunoreactive prostaglandin E2 (i-PGE2) excretion. Although the dose we used has been shown to be effective in vivo, and it inhibited the urinary i-TXB2 excretion on days 5 and 10, it neither inhibited the enhanced production of i-TXB2 on day 1, nor prevented the glomerular influx of monocytes on days 5 and 10. All clinical and histological data tend to be worse rather than better in trapidil-treated animals on days 5 and 10.

Animals↗
PubMed1984

Influence of trapidil derivatives on arachidonic acid- and prostaglandin endoperoxide analogue- induced platelet aggregation and thromboxane A2 formation.

Five selected trapidil derivatives (12456, 12460, 12463, 12464, 12465) inhibited the arachidonic acid(AA)- and prostaglandin endoperoxide analogue(U-46619)- induced platelet aggregation as well as the AA- induced thromboxane A2(TXA2) formation. These effects of the derivatives were generally more markedly expressed than those of trapidil.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1981

[The bioavailability of trapidil from suppositories (author's transl)].

In a study with five healthy persons designed to compare the bioavailability of Trapidil from Rosupol U suppositories with that from Witepsol H 15 suppositories, the availability of Trapidil from the Rosupol U suppositories was inferior in four of the five test subjects. The difference in the amounts of released drug observed in vivo was smaller than that found in vitro.

Adult↗
PubMed1994

[Therapy of ischemic heart disease with Trapidil. Observations with 4,014 patients in medical practice].

METHOD: Within the framework of a user observations study, 4,014 patients with ischemic heart disease were treated with Trapidil and kept under observation for 12 weeks. RESULTS: During the course of therapy, a decrease in the incidence and intensity of attacks of angina pectoris and in the number of weekly short-term nitrate applications was observed. Side effects, most commonly nausea, headache, GI complaints and giddiness, were reported by only 3.8% of the patients. The efficacy of the preparation was assessed to be good or very good in more than 89%, tolerability in more than 90%, of the cases. These results are in accord with the assessment in reports in the international literature to the effect that Trapidil has a good therapeutic action.

Angina Pectoris↗
PubMed2000

Antiproliferative effects of trapidil in vascular smooth muscle cells are associated by inhibition of MAPK and P34(cdc2) activity.

Trapidil (Tra) is a potent coronary vasodilator. Recent studies have shown that Tra possesses antiproliferative activity in glioma cells and vascular smooth muscle cells (VSMCs). These studies were undertaken to determine the effects of Tra on the cell cycle of cultured rat VSMCs, in particular, the effects on two key enzymes responsible for cell-cycle control in cultured rat VSMCs. VSMCs were synchronized by serum deprivation and then stimulated to enter the cell cycle by serum refeeding; the cell-cycle distribution was subsequently measured by flow cytometry, and VSMCs pretreated with 5, 50, and 500 microM Tra showed a decrease in S-phase cell-cycle distribution, 13.1, 18.7, and 58.6%, respectively. In addition, the mitotic activity (S + G2/M) decreased 12.9, 18.7, and 49.6%, respectively after Tra treatment. The protein expression of p34cdc2 was determined by Western blot analysis, and Tra treatment did not affect its expression even at 500 microM. Mitogen-activated protein kinase (MAPK) activity and p34cdc2 kinase activity were assayed by phosphorylation of their specific substrates, myelin basic protein (MBP) and histone H1, after immunoprecipitation. Exposure of VSMCs to Tra resulted in a significant decrease in serum-stimulated MAPK and p34cdc2 activity. The inhibitory rates of 50 and 500 microM Tra on MAPK activity were 59.2 and 80.9%, respectively. Tra concentrations of 5, 50, and 500 microM inhibited p34cdc2 activity by 16.4, 22.6, and 40.8%, respectively. Furthermore, 500 microM Tra inhibited the basal kinase activities of MAPK and p34cdc2 in the cells that were not serum stimulated. These findings demonstrate that Tra significantly decreases the mitotic activity of cultured VSMCs, and that this effect is associated with the inhibitory role of Tra on the kinase activities of MAPK and p34cdc2.

Animals↗
PubMed1998

Inhibitory effect of trapidil on proliferation of cultured rat aortic smooth muscle cells induced by endothelin-1.

AIM: To study the effect of trapidil (Tra) on endothelin-1-induced proliferation of cultured rat aortic vascular smooth muscle cells (VSMC). METHODS: The [3H]TdR incorporation into DNA assay, the number of VSMC, and cell cycle distribution were measured. RESULTS: Pretreated with endothelin-1 100 nmol.L-1, cell number, [3H]TdR uptake, and cell mitogenic activity increased 134% +/- 23%, 210% +/- 70%, and 86% +/- 18%, respectively. This proliferation was inhibited by Tra 5, 50, 500 mumol.L-1. The inhibitory rates were 12%-48%, 35%-54% and 15%-47%, respectively. Tra did not influence the proliferation of VSMC without endothelin-1 pretreatment. CONCLUSION: Tra antagonized the proliferation of VSMC induced by endothelin-1.

Animals↗