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At least 19 recordsLinked to original sources
PubMed1989

[Adjuvant therapy of non-small cell bronchial cancer with mopidamol].

Between January 1982 and April 1986 a double-blind randomized placebo controlled study of mopidamol, employed as adjunct therapy to surgery in patients with non-small cell bronchial carcinoma, was performed at 7 hospitals. The main criteria were occurrence of metastases and survival. Mopidamol was given perioperatively at a dose of 2 x mg i.v. daily, and postoperatively orally at a dose of 3 x 500 mg daily. The treatment period was scheduled to at least 2 years and in some of the patients was prolonged to 3 years. The standard therapy of each individual center was given as basic therapy. A total of 270 patients were included in the study, 147 in the placebo and 123 in the mopidamol group. By the end of the study 52 deaths from metastases had occurred in the placebo group (35%) compared with only 32 (26%) in the mopidamol group. This difference is statistically significant at p less than 0.05 with the one-sided test. A comparison of life-tables according to Kaplan-Meier shows a statistically significant difference in favour of the group treated with mopidamol (savage p less than 0.05). Cox's multivariate analysis confirmed the statistically significant difference in favour of the group treated with mopidamol, the inclusion of the risk factors tumour stage and histology in the evaluation results in a p-value of 0.02. With respect to the incidence of metastases there were no appreciable differences between the treatment groups. The incidence of side effects or undesired events was equal in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Differential effects of the pyrimido-pyrimidine derivatives, dipyridamole and mopidamol, on platelet and vascular cyclooxygenase activity.

The chronic administration of 10 mg/kg/day of dipyridamole to rats produced 33.7% inhibition of platelet aggregation induced with ADP and a 93% increase in 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in vascular samples, versus saline-treated rats. Mopidamol, 8.3 mg/kg/day, caused 50.6% inhibition of ADP-induced platelet aggregation, 37.6% inhibition of aggregation induced with arachidonic acid, a 47.6% decrease in serum levels of thromboxane B2 and a 23.7% increase in the vascular production of 6-keto-PGF1 alpha, versus saline-treated rats. Dipyridamole showed a higher in vitro anti-aggregating effect in whole blood (IC50 6.6 microM) than in platelet-rich plasma (PRP) (IC50 210 microM), when ADP was used as inducer, and had no effect in the presence of arachidonic acid. Mopidamol exerted a similar effect in whole blood (IC50 3.7-20 microM, depending on the inducer) and PRP (IC50 11-17.3 microM), and showed a dose-dependent inhibition of platelet aggregation and thromboxane B2 synthesis induced with arachidonic acid (IC50 16.8-22.3 microM). Mopidamol also inhibited enzymatically induced lipid peroxidation) (IC50 89 +/- 5.9 mumol/L) and had no effect on free radical-induced lipid peroxidation. The dose-dependent increase in 6-keto-PGF1 alpha in vascular samples after incubation with dipyridamole showed a negative linear correlation with inhibition of lipid peroxidation (r2 = 0.77). It is concluded that the phosphodiesterase inhibitors, dipyridamole and mopidamol, interfere in a different manner with platelet function. It seems that mopidamol may also exert a selective effect on platelet thromboxane synthesis.

Animals↗
PubMed1996

The pyrimido-pyrimidine derivatives, dipyridamole, mopidamol and RA-642, prevent from retinal vascular defects in experimental diabetes mellitus.

We compared the effects of dipyridamole, RA-642, and mopidamol on platelet activity and thromboxane/prostacyclin balance in relation to the degree of retinal vascularization in a model of experimental streptozotocin-induced diabetes in rats. After 3 months, collagen-induced platelet aggregation in whole blood was 25% higher in diabetic animals than in nondiabetics. Dipyridamole inhibited 43% platelet aggregation, mopidamol 39%, and RA-642 36%. Platelet production of thromboxane B2 was 87% higher in untreated diabetic rats. Mopidamol and RA-642 produced a 46% and 41% inhibition of thromboxane B2. Dipyridamole did not inhibited thromboxane B2 synthesis. Aortic production of 6-keto-PGF1 alpha was 43% lower in untreated diabetic animals and showed no change after treatment with either mopidamol or RA-642. In contrast, dipyridamole caused a 90% increase in aortic production of prostacyclin. Computerized analysis of retinal vascularization showed that untreated diabetic rats had a 81% decrease in the area occupied by peroxidase-labelled vessels as compared with nondiabetics. Treatment with dipyridamole, mopidamol, and RA-642 caused 2.5-fold, 2.8-fold and four-fold increases, respectively, in the percentage of retinal surface occupied by peroxidase-labelled vessels. Differences in retinal vascularization between diabetic animals given RA-642 and nondiabetic controls were negligible.

Animals↗
PubMed1984

Effects of a new antitumor compound, mopidamol, on thymidine and 2-deoxyglucose transport in leukaemic L 1210 cells.

The effects of 2,2',2",2"'-[(4-piperidinopyrimido[5,4-d]pyrimidine-2,6- diyl)dinitrilo]-tetraethanol (mopidamol, RA-233), a drug with antitumour properties, have been studied on membrane transports of L 1210 cells grown in culture. The results show that mopidamol is an inhibitor of thymidine and 2-deoxyglucose transport at concentrations less than or equal to 10(-4) mol/l. The inhibitory effect on cancer cells occurs as soon as 20 s after contact with the drug. Lineweaver and Burk's plots demonstrate a non-competitive type inhibitory effect on membrane transports. In addition, thymidine incorporation in DNA is decreased in the presence of mopidamol.

Animals↗
PubMed1984

Potentiation of the cell growth inhibitory effect of beta interferon by mopidamole.

It was suggested that the antitumor effect of the interferons is based in part on their ability to stimulate increased cAMP production. We have explored the interaction of human fibroblastic beta interferon (HFIF) with a cAMP decomposition inhibitory pyrimido-pyrimidine derivative, Mopidamole (RA-233) in cultures of neoplastic and normal cell lines. Mopidamole potentiated the growth inhibitory effect of HFIF in cultures of ES-1 malignant melanoma cells, LNCaP prostatic carcinoma cells, RT-4 transitional carcinoma cells, HT-29 colon adenocarcinoma cells and in diploid fibroblast cells.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Inhibition of ferrous-induced lipid peroxidation by dipyridamole, RA-642 and mopidamol in human lung tissue.

1. The in vitro production of ferrous-induced lipid peroxidation was 5.71 times higher in rat lung tissue than in human lung membranes. 2. The pyrimido-pyrimidine derivative RA-642 shows a more potent inhibition of ferrous-induced lipid peroxidation than dipyridamole; mopidamol had no effect. All the compounds showed higher anti-peroxidative effect in rat than in human lung tissue.

Adult↗
PubMed1988

Effect of mopidamol on survival in carcinoma of the lung and colon: final report of Veterans Administration Cooperative Study No. 188.

Mopidamol (RA-233), a derivative of dipyridamole, is a phosphodiesterase inhibitor that has been shown previously to limit progression of malignancy in certain experimental animal models and in a pilot study in humans. RA-233 plus chemotherapy was compared with chemotherapy alone in a 5-year double-blind trial involving 719 patients with advanced carcinomas of the lung and of the colon. RA-233 treatment was associated with a statistically significant prolongation of survival in patients with non-small cell lung cancer (N-SCLC) limited to one hemithorax and with reduction in mean plasma fibrogen concentration. RA-233 was not toxic. The favorable effects on survival could not be explained by any factor other than the RA-233 treatment. In other tumor categories tested, no differences in survival were observed. These results suggest that RA-233 is useful in the treatment of N-SCLC of limited extent. They also suggest that therapeutic intervention aimed at modified intracellular pathways might constitute a novel investigative approach to the treatment of cancer.

Carcinoma↗
PubMed1987

Inhibitory action of flurbiprofen and mopidamole on tumor lung metastasis formation in mice.

Flurbiprofen, 0.25 mg/kg, administered to mice orally once daily during 3 days prior to an iv transplantation of Lewis lung carcinoma cells, protected 50%-57% of experimental animals from the formation of lung tumor colonies. With the daily dose of 1.0 mg/kg, this effect was less pronounced. Mopidamole, twice daily 90 mg/kg orally during 3 days, did not have this effect.

Administration, Oral↗
PubMed1988

Mopidamol.

Explore the source record for details and available documents.

Carcinoma, Non-Small-Cell Lung↗
PubMed1983

[Modification of metastasis formation by inhibition of platelet aggregation. Experimental and clinical results].

Our clinical study to prevent relapse and metastases in several sarcomas and malignant lymphomas of the head and neck region with a long-term treatment with mopidamole was initiated in 1972 because the pyrimido-pyrimidine derivative was shown to inhibit platelet aggregation in vivo and to increase significantly the circulation time of intravenously injected, 32P-labelled Ehrlich ascites tumour cells in mouse blood. The aggregation of platelets to circulating tumour cells and their subsequent adhesion to vascular endothelium in turn appeared to be part of the early stages of the metastatic process. It seems, however, that other related mechanisms are also involved in the clinical results obtained. Mopidamole, as other related derivatives, probably inhibits platelet aggregation by inhibition of PDE-induced decomposition of cAMP and may stimulate the synthesis and/or release of prostacyclin from the vessel wall which in turn activates adenylate cyclase involved in cAMP synthesis. The latter mechanism was definitely shown only for the related pyrimido-pyrimidine derivative dipyridamole, the methyl-xanthine derivative pentoxifylline and the methyl-pyrazoline derivative nafazatrom. The increase of cAMP levels by mopidamole results in an inhibition of 3H-thymidine incorporation into human neoplastic cells and a direct inhibition of its mitotic rate. The adding of mopidamole to a culture of a human promyelocytic leukemic cell line promotes a reverse transformation of the malignant cells to normal which appears to be a permanent phenotypic change. Furthermore, mopidamole was shown to diminish significantly spontaneous lung metastases in syngenic Wilms' tumor (nephroblastoma) of the rat, the C1300-neuroblastoma of the mouse and the HM-Kim mammary carcinoma of the rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

The pyrimido-pyrimidine derivatives, dipyridamole and RA-642, reduce opacification of crystalline lens in diabetic rats.

We assessed the effect of dipyridamole, RA-642 and mopidamol, on lenticular opacities in a model of experimental diabetic cataracts in rats. All three pyrimido-pyrimidine derivatives caused a statistically significant reduction of opacification in crystalline lens as compared with untreated diabetic animals. The production of superoxide anions (phenazine methosulphate [PMS]-induced nitroblue tetrazolium [NBT] reduction) showed a decrease of 81.6%, 78.9% and 1.8% in lens tissue homogenates from rats treated with dipyridamole, RA-642 and mopidamol, respectively. Dipyridamole and RA-642 produced a statistically significant inhibition (50% and 64.8%, respectively) of lipid peroxidation (ferrous sulphate and ascorbic acid [FeAs]-induced malondialdehyde [MDA] production) as compared with the group of untreated diabetic rats. Mopidamol did not exert any inhibitory effect on lipid peroxidation. There was a statistically significant correlation between opacification of lens and PMS-induced NBT reduction and FeAs-induced MDA production. We conclude that the protective effect of dipyridamole and RA-642 from free radical damage to crystalline lens in the model of experimental diabetes used in this study, is the result of the antioxidant action of these compounds. The effect exerted by mopidamol, however, suggest a possible complementary effect of the pyrimido-pyrimidine derivatives through interaction with other mechanisms (e.g., the sorbitol pathway) implicated in the development of cataracts.

Animals↗
PubMed1986

Antimetastatic effect of flurbiprofen and other platelet aggregation inhibitors.

In the present study, we have examined the antimetastatic effect of flurbiprofen, a nonsteroidal antiinflammatory drug, on spontaneous metastases formation in mice bearing Lewis lung carcinoma and these results were compared with effects of other inhibitors of platelet function (mopidamole, dipyridamole, pentoxifylline). Flurbiprofen decreased significantly spontaneous metastases formation in a dose-depending manner. From the results obtained, it appears that the treatment with flurbiprofen, either on days 1-8 or days 1-21, was similarly effective. In mopidamole treated groups the number of animals with lung metastases was significantly decreased. This effect was not observed after treatment with dipyridamole or pentoxifylline.

Animals↗
PubMed1987

Polymeric inhibitors of platelet aggregation. II. Copolymers of dipyridamole and related drugs with N-vinylpyrrolidone.

A study has been made of the behaviour of the drugs dipyridamole and mopidamol (RA 233) attached to poly(N-vinylpyrrolidone). The inhibitory activities towards platelet aggregation induced by ADP or platelet activation factor (PAF) in sheep plasma have been examined and found to exceed the activities of the parent drugs, by factors up to 20. At the same time the abilities of the polymer-bound drugs in potentiating prostaglandin-type anti-aggregatory activities are much lower than those of the unattached drugs. The observations are explained in terms of polymer adsorption on to the platelet membranes, producing a high surface concentration of the drugs with consequent high inhibitory action. Intracellular action, such as the inhibition of phosphodiesterase, is reduced by the difficulty experienced by the polymeric drug in passing through the membrane, so that potentiation of prostaglandin activity, particularly against PAF, becomes small. A terpolymer containing units of dipyridamole and the prostaglandin analogue 5-(6-carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl)hydantoin (245C) shows a degree of 'self-potentiation'.

Adenosine Diphosphate↗
PubMedDate not supplied

The pyrimido-pyrimidine derivative RA-642: a potent inhibitor of ferrous-induced lipid peroxidation in cell membranes.

The effects of three pyrimido-pyrimidine derivatives (RA-642, dipyridamole and mopidamol) on hydroxyl anion-induced lipid peroxidation in cell membranes from liver, brain, kidney, lung and heart rat tissue were studied using d-alpha-tocopherol as standard for lipid peroxidation. Ferrous sulfate and ascorbic acid (FeAs) were used to induce lipid peroxidation via the formation of hydroxyl anions. The products resulting from the reaction with thiobarbituric acid were taken to be indicators of lipid peroxidation. Thiobarbituric acid reactive substances (TBARS) were produced by different rat tissues in the following sequence: brain greater than liver greater than kidney greater than heart greater than lung. Dose-response and time-response curves were plotted for all compounds. Inhibiting concentrations, 50% (IC50), ranged from 0.3-1.4 microM for RA-642, and 2.5 and 4.6 microM for dipyridamole. In liver mitochondrial membranes, IC50s of these compounds were 0.4 +/- 0.2 and 5.8 +/- 1.2 microM, respectively. At 15 min after beginning TBARS production, dipyridamole and RA-642 did not exert any inhibitory effect.

Animals↗
PubMed1984

Antineoplastic effect of the pyrimido-pyrimidine derivative: RA 233.

A number of normal and neoplastic human cell lines in culture were studied by cell count and 3H thymidine incorporation for growth inhibitory effect by the pyrimido-pyrimidine derivative RA-233 (mopidamole). There was more inhibition when the drug was added to the culture in the lag phase than in the logarithmic growth phase. There was more inhibition (particularly at low doses) of the neoplastic cell lines than of the non-neoplastic cell lines.

Antineoplastic Agents↗
PubMed1992

Dipyridamole enhances an anti-proliferative effect of interferon in various types of human tumor cells.

The anti-proliferative activity of human interferon (HuIFN) was enhanced by dipyridamole, 2,6-bis-(diethanolamino)-4,8-dipiperidinopyrimido-[5,4-d]-py rimidine, when tested against various human tumor cell lines, including KT (breast carcinoma), PLC/PRF/5 (hepatoma), MGC-I, U251-SP and T98 (glioma), HAC-2 and SHIN-3 (ovarian carcinoma), and MM-ICB (melanoma). The enhancement occurred irrespective of the kind of HuIFN used (alpha, beta or gamma) and the original degree of susceptibility of the cells to HuIFN. Even low doses down to 0.01 microM of dipyridamole that had no intrinsic anti-proliferative activity could enhance the effect of HuIFN. The enhancement of HuIFN effects seems not to be caused by induction of HuIFN production, because neither anti-viral activity nor HuIFN antigens were detected in culture medium in cells treated with dipyridamole. Mopidamole, a derivative of dipyridamole lacking one piperidine residue, produced little enhancement of the effects of HuIFN. Among ovarian cancer cell lines tested, the enhancement of the activity of HuIFN by dipyridamole for HAC-2 and SHIN-3 cells was equivalent to or greater than that for 3 chemotherapy agents (adriamycin, vincristine, and a camptothecin derivative). However, neither HOC-21 ovarian cancer cells nor HEC-1 endometrial adenocarcinoma cells were susceptible to any combinations. When MGC-1, U251-SP, and HAC-2 cells were injected into nude mice, the growth of tumors was more markedly inhibited by the subcutaneous administration of HuIFN in combination with oral administration of dipyridamole than by the HuIFN alone. Thus, this combination therapy seems to be worth trying for human cancer, although the enhancement of the effects of HuIFN by dipyridamole varied among the cell lines examined.

Animals↗