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Journal of the National Cancer Institute Jun 1988
Topics: Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Mopidamol; Pyrimidines
PubMed: 2835491
DOI: 10.1093/jnci/80.7.532 -
Journal of the National Cancer Institute Mar 1988
Topics: Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Mopidamol; Oncogenes; Pyrimidines
PubMed: 2830406
DOI: 10.1093/jnci/80.2.77 -
Thrombosis Research Feb 1996We compared the effects of dipyridamole, RA-642, and mopidamol on platelet activity and thromboxane/prostacyclin balance in relation to the degree of retinal... (Comparative Study)
Comparative Study
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.
Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Dipyridamole; Epoprostenol; Male; Mopidamol; Neovascularization, Pathologic; Platelet Aggregation Inhibitors; Pyrimidines; Rats; Rats, Wistar; Thromboxanes
PubMed: 8928090
DOI: 10.1016/0049-3848(96)00004-7 -
Journal of the National Cancer Institute Mar 1988Mopidamol (RA-233), a derivative of dipyridamole, is a phosphodiesterase inhibitor that has been shown previously to limit progression of malignancy in certain... (Clinical Trial)
Clinical Trial
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.
Topics: Carcinoma; Clinical Trials as Topic; Colonic Neoplasms; Cyclic AMP; Humans; Lung Neoplasms; Mopidamol; Oncogenes; Prospective Studies; Pyrimidines; Random Allocation
PubMed: 2830407
DOI: 10.1093/jnci/80.2.90 -
Biochemical Pharmacology Jan 1994The 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... (Comparative Study)
Comparative Study
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.
Topics: Animals; Blood Platelets; Blood Vessels; Cyclooxygenase Inhibitors; Dipyridamole; Enzyme Activation; Epoprostenol; Humans; Lipid Peroxidation; Male; Mopidamol; Platelet Aggregation; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Wistar; Thromboxane A2
PubMed: 8304965
DOI: 10.1016/0006-2952(94)90008-6 -
General Pharmacology Jul 19961. 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...
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.
Topics: Adult; Aged; Animals; Antioxidants; Dipyridamole; Female; Ferrous Compounds; Humans; In Vitro Techniques; Lipid Peroxidation; Lung; Male; Malondialdehyde; Middle Aged; Mopidamol; Pyrimidines; Rats; Rats, Wistar; Thiobarbituric Acid Reactive Substances; Vitamin E
PubMed: 8842690
DOI: 10.1016/0306-3623(95)02098-5 -
Pneumologie (Stuttgart, Germany) Jun 1989Between 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... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
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)
Topics: Aged; Carcinoma, Non-Small-Cell Lung; Clinical Trials as Topic; Combined Modality Therapy; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mopidamol; Prospective Studies; Pyrimidines; Random Allocation
PubMed: 2547216
DOI: No ID Found -
Arzneimittel-Forschung 1984The 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...
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.
Topics: Animals; Antineoplastic Agents; Cells, Cultured; Deoxy Sugars; Deoxyglucose; Kinetics; Leukemia L1210; Mice; Mopidamol; Pyrimidines; Thymidine
PubMed: 6538421
DOI: No ID Found -
Thrombosis Research Jan 1995
Topics: Adult; Cell Communication; Dipyridamole; Endothelium, Vascular; Humans; In Vitro Techniques; Male; Mopidamol; Perfusion; Platelet Aggregation; Platelet Aggregation Inhibitors
PubMed: 7701482
DOI: 10.1016/0049-3848(95)90869-h -
Cancer Treatment Reviews Dec 1985The role of antiplatelet drugs in relation to their potential antimetastatic activities has been reviewed and the effects of two pyrimido-pyrimidine derivatives (RX-RA69... (Review)
Review
The role of antiplatelet drugs in relation to their potential antimetastatic activities has been reviewed and the effects of two pyrimido-pyrimidine derivatives (RX-RA69 and RX-RA85) with strong antiplatelet activities investigated in metastasizing tumour models. The routes of administration and drug dosages were always chosen in such a way that good antiplatelet activities were obtained. RX-RA69 (20 mg/kg/day) given in the drinking water had no effect on spontaneous metastasis of Lewis lung carcinoma. RX-RA85 (20 mg/kg/day) did not influence spontaneous metastasis of B16 melanoma. On the other hand, giving RX-RA85 (8 mg/kg) daily i.p. to Lewis lung carcinoma bearing mice significantly increased the number of lung metastases but had no significant effect on primary tumour implant growth. Pretreating mice orally with 20 mg/kg RX-RA85 1 h before i.v. injection of B16 melanoma cells had no significant effect on lung colony number or distribution of extrapulmonary tumours while injecting the same dosage of RX-RA85 i.v. 1-2 h before tumour-cell injection decreased lung colony formation, but increased extrapulmonary tumour burden. This investigation like many others does not support the importance of platelets in metastasis formation.
Topics: Animals; Blood Platelets; Cyclic AMP; Humans; Lung Neoplasms; Melanoma; Mice; Mopidamol; Neoplasm Metastasis; Platelet Aggregation; Pyrimidines; Rats
PubMed: 3009013
DOI: 10.1016/0305-7372(85)90006-4