A comparison between platelet aggregation and atp secretion induced by collagen and by paf acether and their inhibition by phenylbutazone, sulphinpyrazone and its metabolites

Ambler, J. E.; Wallis, Robert B.

doi:10.1016/0049-3848(83)90455-3

Cited by 9 publications

(2 citation statements)

References 13 publications

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“…Materials CGS 12970, 3-methyl-2 (3-pyridyl)-l-indoleoctanoic acid, was synthesized by Dr B. Renfroe, CIBA-GEIGY Corporation, Ardsley, N.Y. and dissolved in polyethylene glycol 400 (PEG 400) for oral administration to laboratory animals. Platelet activating factor was synthetic l-0-hexadecyl-2-0-acetyl-snglyceryl-3-phosphorylcholine from CIBA-GEIGY Ltd, Basle, Switzerland and was prepared for use as previously described (Ambler & Wallis, 1983). The following drugs were also used: ADP, arachidonic acid, 5-hydroxytryptamine (5-HT), thrombin (all obtained from Sigma) and U 46619 (9,1 1-dideoxy,9x-…”

Section: Discussionmentioning

confidence: 99%

“…Platelet activating factor was synthetic l-0-hexadecyl-2-0-acetyl-snglyceryl-3-phosphorylcholine from CIBA-GEIGY Ltd, Basle, Switzerland and was prepared for use as previously described (Ambler & Wallis, 1983). The following drugs were also used: ADP, arachidonic acid, 5-hydroxytryptamine (5-HT), thrombin (all obtained from Sigma) and U 46619 (9,1 1-dideoxy,9x- …”

Section: Animal Modelsmentioning

confidence: 99%

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CGS 12970: a novel, long acting thromboxane synthetase inhibitor

Ambler

Butler

Ku³

et al. 1985

British J Pharmacology

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1 CGS 12970 is a potent selective inhibitor of human platelet thromboxane synthestase in vitro (IC50 = 12 nM). It is four orders of magnitude less potent as an inhibitor of sheep seminal vesicle cyclooxygenase, bovine aorta prostacyclin synthetase and human leucocyte 15-lipoxygenase. 2 The compound inhibited collagen-induced thromboxane B2 production by human platelets in vitro without an effect on the accompanying platelet aggregation induced by collagen, ADP, platelet activating factor, thrombin, arachidonic acid or the prostaglandin mimetic, U 46619. 3 Administration of CGS 12970 to rats inhibited collagen-induced thromboxane B2 production but had no effect on platelet aggregation ex vivo. It also had no effect on platelet aggregation induced by thrombin or on plasma clotting times. 4 A single oral dose of 1 or 3 mg kg-' to rabbits inhibited thromboxane B2 production in clotting blood ex vivo for 12 or 24 h respectively. 5 CGS 12970 inhibited thromboxane B2 production in vivo induced by intravenous administration of collagen to rats or calcium ionophore to guinea-pigs. In both cases there was a concomitant elevation of immunoreactive 6-keto-prostaglandin Flr. but no effect on the induced thrombocytopenia.6 As with other thromboxane synthetase inhibitors, CGS 12970 prolonged tail bleeding time in the rat. However, CGS 12970 was not as potent as other thromboxane synthetase inhibitors in this test. 7 In addition to these usual effects of thromboxane synthetase inhibitors, CGS 12970 inhibited the thrombocytopenia induced by the Forssman reaction or ADP administration. In these tests the effect of the compound was of short duration. 8 CGS 12970 had no effect on the thrombocytopenia associated with the Arthus reaction which distinguishes it from cyclo-oxygenase inhibitors. It also had no effect on thrombus formation on a cotton thread in an arteriovenous shunt in the rat.

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Section: Discussionmentioning

confidence: 99%

Section: Animal Modelsmentioning

confidence: 99%