dinoprost and dazoxiben

dinoprost has been researched along with dazoxiben* in 6 studies

Other Studies

6 other study(ies) available for dinoprost and dazoxiben

ArticleYear
Effects of the selective inhibition of platelet thromboxane synthesis on the platelet-subendothelium interaction.
    British journal of pharmacology, 2002, Volume: 137, Issue:7

    1. Drugs that inhibit TxA(2) synthesis are used to reduce platelet aggregation. The aim of this study was to compare the effects of a cyclo-oxygenase (COX) inhibitor (acetylsalicylic acid, ASA), a thromboxane synthetase (TxS) inhibitor (dazoxiben) and a dual TxS inhibitor and TxA(2) receptor blocker (DT-TX 30) on platelet aggregation and the platelet-subendothelium interaction in flow conditions. 2. The techniques used in this in vitro study were platelet aggregometry in whole blood, and measurement of platelet thromboxane B(2) and prostaglandin E(2) production and leucocyte production of 6-keto-PGF(1alpha). The platelet-subendothelium interaction was evaluated in rabbit aorta subendothelium preparations exposed to flowing blood at a shear stress of 800 s(-1). Morphometric methods were used to calculate the percentage of subendothelium occupied by platelets. 3. The 50% inhibitory concentration (IC(50)) of DT-TX 30 in whole blood was in the range of 10(-7) micro M (induced with collagen or arachidonic acid) to 10(-5) micro M (induced with thrombin) or 10(-4) (induced with ADP). IC(50) values under all experimental conditions were lower with DT-TX 30 than with ASA. For thromboxane B(2) the IC(50) were: ASA 0.84+/-0.05 micro M, dazoxiben 765+/-54 micro M, DT-TX 30 8.54+/-0.60 micro M. Prostaglandin E(2) was inhibited only by ASA (IC(50) 1.21+/-0.08 micro M). Leucocyte 6-keto-PGF(1alpha) was inhibited by ASA (IC(50) 6.58+/-0.76 micro M) and increased by dazoxiben and DT-TX 30. The greatest reduction in percentage subendothelial surface occupied by platelets after blood perfusion was seen after treatment with DT-TX 30 in the range of concentrations that inhibited collagen-induced platelet aggregation (control group: 31.20+/-3.8%, DT-TX 30 at 0.1 micro M: 10.71+/-0.55%, at 1.0 micro M: 6.53+/-0.44%, at 5.0 micro M; 1.48+/-0.07%). All three drugs reduced thrombus formation, although ASA (unlike dazoxiben or DT-TX 30) increased the percentage surface occupied by adhesions. 4. In conclusion, the effect of specific blockage of TxS together with blockage of membrane receptors for TxA(2) can surpass the effect of ASA in inhibiting the platelet-subendothelium interaction in flow conditions.

    Topics: 6-Ketoprostaglandin F1 alpha; Adult; Animals; Aspirin; Blood Platelets; Chlorobenzenes; Cyclooxygenase Inhibitors; Dinoprost; Dose-Response Relationship, Drug; Endothelium, Vascular; Humans; Imidazoles; Male; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors; Pyridines; Rabbits; Receptors, Thromboxane; Thromboxane B2; Thromboxane-A Synthase; Thromboxanes

2002
Bronchopulmonary actions of 1-(1,2,3,4-tetrahydro-1-naphthylenyl)-1H-imidazole, nitric acid salt (LY150310), a substituted imidazole, in the guinea pig.
    The Journal of pharmacology and experimental therapeutics, 1993, Volume: 267, Issue:2

    1-(1,2,3,4-tetrahydro-1-naphthylenyl)-1H-imidazole, nitric acid salt (LY150310), was examined for bronchodilator activity in the guinea pig. In guinea pig tracheal preparations, LY150310 competitively antagonized the contractile effects of exogenous histamine and blocked the histamine-mediated component of contractions produced by ovalbumin challenge. LY150310 had little effect on the nonhistamine component of ovalbumin-induced contractions of lung parenchymal strips, but it enhanced the production of prostaglandin (PG) E2 and PGF2 alpha although it partially inhibited thromboxane B2 formation. In other studies, in which postmortem pulmonary gas trapping was used as an index of in vivo airway obstruction, i.v. LY150310 dose-dependently inhibited the bronchospasm produced by aerosols of the divalent cationic ionophore A23187, histamine, 5-hydroxytryptamine, leukotriene D4, methacholine, ovalbumin or platelet activating factor. LY150310 was equal to or more potent than aminophylline in all test systems. Also, orally administered LY150310 inhibited the airway obstruction produced by selected challenge aerosols. In ex vivo studies, LY150310 elevated PGE2 and tended to decrease thromboxane B2 in sodium arachidonate-stimulated whole blood. However, PGE2 and other cyclooxygenase products did not appear to account for in vivo bronchodilation, because combining LY150310 and piroxicam did not alter inhibition of A23187-induced airway obstruction. Our results demonstrate that LY150310 reduces airway obstruction caused by a variety of bronchoconstrictive agents, including A23187 and ovalbumin. Although this substituted imidazole appears to have activity as a histamine H1-receptor antagonist and can alter prostanoid concentrations in vitro and in vivo, its mode of bronchodilation is unclear.

    Topics: Aerosols; Animals; Antineoplastic Agents; Bronchoconstriction; Bronchoconstrictor Agents; Dinoprost; Dinoprostone; Drug Interactions; Eicosanoids; Guinea Pigs; Imidazoles; In Vitro Techniques; Lipopolysaccharides; Lung; Male; Piroxicam; Tetrahydronaphthalenes; Thromboxane B2; Trachea

1993
Prostaglandins and human platelet aggregation. Implications for the anti-aggregating activity of thromboxane-synthase inhibitors.
    Biochemical pharmacology, 1985, Feb-01, Volume: 34, Issue:3

    Selective pharmacological blockade of thromboxane-synthase in human platelets by dazoxiben resulted in the reorientation of cyclic-endoperoxides towards PGE2, PGD2 and PGF2 alpha. At concentrations which can be reached when thromboxane-synthase is inhibited, PGE2 (100-500 nM) exerted a marked, concentration-dependent pro-aggregatory effect. This required the formation of endogenous or the addition of exogenous endoperoxides and was prevented by PGD2 or 13-aza-prostanoic acid, a selective antagonist of PGH2/TxA2 receptors. The anti-aggregating effect of PGD2 was evident at concentrations lower than those obtained in dazoxiben-treated platelets. It is proposed that in the absence of TxA2 generation, a combination of endoperoxides and PGE2 may result in normal aggregation. The latter may be inhibited by PGD2. No interference of PGF2 alpha on platelet function could be shown.

    Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adenosine Diphosphate; Arachidonic Acid; Arachidonic Acids; Aspirin; Blood Platelets; Dinoprost; Dinoprostone; Drug Synergism; Humans; Imidazoles; Oxidoreductases; Platelet Aggregation; Prostaglandin D2; Prostaglandin Endoperoxides; Prostaglandin Endoperoxides, Synthetic; Prostaglandins; Prostaglandins D; Prostaglandins E; Prostaglandins F; Prostanoic Acids; Thromboxane B2; Thromboxane-A Synthase

1985
Pharmacologic inhibition of thromboxane synthetase and platelet aggregation: modulatory role of cyclooxygenase products.
    Blood, 1984, Volume: 63, Issue:6

    Dazoxiben , an imidazole-derived selective inhibitor of thromboxane A2 (TxA2) synthetase, prevented TxB2 synthesis in vitro in platelet-rich plasma from 16 normal subjects. Inhibition of TxB2 synthesis was accompanied by increased generation of PGE2, PGF2 alpha, and PGD2, as shown by radioimmunoassay, thin-layer radiochromatography, and high-resolution gas chromatography-mass spectrometry. Even at dazoxiben concentrations (40-80 microM) above those inhibiting TxB2 synthesis, platelet aggregation induced by threshold concentrations of arachidonic acid was inhibited in only 4 of 16 subjects, referred to as responders. The remaining 12 individuals were defined as nonresponders. The aggregating effect of arachidonic acid and of the prostaglandin-endoperoxide analog U-46619 was potentiated by PGE2 and prevented by PGD2 at concentrations within the range of those detected in dazoxiben -treated platelet-rich plasma. The antiaggregating effect of dazoxiben was counteracted by PGE2 (in responders) and was potentiated by PGD2 (in nonresponders). Platelets from responders and nonresponders did not differ in the amount of immunoreactive PGE2 material or in their sensitivity to U-46619 or PGD2. It is concluded that inhibition of thromboxane synthetase does not per se prevent platelet aggregation. The functional result of thromboxane suppression appears to be modulated by an interplay of the prostaglandin-endoperoxides, PGE2 and PGD2, which are formed in excess.

    Topics: Adult; Arachidonic Acid; Arachidonic Acids; Chromatography, Gas; Chromatography, Thin Layer; Dinoprost; Dinoprostone; Female; Humans; Imidazoles; Male; Mass Spectrometry; Oxidoreductases; Platelet Aggregation; Prostaglandin D2; Prostaglandins D; Prostaglandins E; Prostaglandins F; Radioimmunoassay; Thromboxane A2; Thromboxane-A Synthase; Thromboxanes

1984
Spasmogenic activity of C5adesArg anaphylatoxin on guinea pig lung parenchymal strips: sensitivity of the leukotriene-mediated component to cyclooxygenase inhibitors.
    Biochemical and biophysical research communications, 1984, Dec-28, Volume: 125, Issue:3

    The leukotriene-dependent component of C5adesArg-induced contractile activity on guinea pig lung parenchymal strips is inhibited by cyclooxygenase inhibitors. Indomethacin simultaneously increased leukotriene release while inhibiting both cyclooxygenase-dependent mediator release and the contractile force generated. Tissue responses to LTC4 and LTD4 are also inhibited by cyclooxygenase blockade, while contractions induced by the thromboxane A2 analog, U-46619, histamine or acetylcholine are not affected. These data indicate a functional role for cyclooxygenase metabolites in leukotriene-induced contractile responses in lung.

    Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Complement C5; Complement C5a, des-Arginine; Cyclooxygenase Inhibitors; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; Guinea Pigs; Imidazoles; Indomethacin; Lung; Muscle Contraction; Piroxicam; Prostaglandins E; Prostaglandins F; SRS-A; Thiazines; Thromboxane B2

1984
Manipulation of the local thromboxane and prostacyclin balance in vivo by the antithrombotic compounds dazoxiben, acetylsalicylic acid and nafazatrom.
    Biochemical pharmacology, 1983, Sep-15, Volume: 32, Issue:18

    We have developed an experimental model for the study of local prostaglandin production by platelets and the vessel wall following stimulation 'in vivo'. A nylon thread was inserted into the external jugular vein of rabbits; its presence did not induce an occluding thrombus. Thromboxane (TXB2) values in the blood, sampled through the facial vein, immediately distal to the stimulus, rose and remained high for at least 4 hr, while 6-keto prostaglandin (PG) F1 alpha levels, after a first increase, gradually returned to normal ('exhaustion' of the endothelial cells?). No changes were observed in the contralateral jugular vein without thread. After infusion via the femoral vein of 10 mg/kg dazoxiben, a thromboxane synthetase inhibitor, local TXB2 production was completely abolished, whereas 6-keto PGF1 alpha formation no longer returned to basal values, but tended to increase. This leads to the conclusion that upon inhibition of TXB2 formation endoperoxide metabolism is reoriented 'in vivo' towards prostacyclin, and this mainly at the site where platelets are activated. Injection of 100 mg/kg lysine acetylsalicylic acid resulted in complete inhibition of TXB2 and 6-keto PGF1 alpha formation, the latter, however, slowly recovering with time. The administration of nafazatrom to the animals did not influence the local TXB2 changes, but partially prevented the decline of 6-keto PGF1 alpha with time. The antithrombotic properties of this drug thus could be related to protection of the endothelial cells from 'exhaustion'.

    Topics: Animals; Aspirin; Dinoprost; Drug Interactions; Fibrinolytic Agents; Functional Laterality; Imidazoles; Kinetics; Male; Prostaglandins F; Pyrazoles; Pyrazolones; Rabbits; Thromboxane B2; Thromboxane-A Synthase; Thromboxanes

1983