Investigations on a selective non-prostanoic thromboxane antagonist, BM 13.177, in human platelets

Patscheke, Heinrich; Stegmeier, K

doi:10.1016/0049-3848(84)90163-4

Cited by 99 publications

(30 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This reaction is known to require TXA2 (Charo et al, 1977) and is prevented in the same model by thromboxane synthetase inhibitors (Thiemermann & Schrdr, 1984). Furthermore, BM 13.177 has been found to antagonize platelet reactions that are dependent upon the mobilization ofendogenous arachidonic acid or, alternatively, induced by thromboxane mimetics in the absence of significant alterations in thromboxane biosynthesis (Patscheke & Stegmeier, 1984). These and other data clearly demonstrate the potency of BM 13.177 in blocking platelet thromboxane receptors in vivo at doses that do not alter endogenous thromboxane concentrations.…”

Section: General Haemodynamics and Ecgmentioning

confidence: 69%

“…BM 13.177, while antagonizing platelet secretion including the release of platelet derived vasoconstrictors such as 5-hydroxytryptamine (5-HT; Patscheke & Stegmeier, 1984;Latta et al, 1985), did not break up ischaemia-induced platelet aggregates. It has been reported that treatment of LAD-occluded cats with the thromboxane synthetase inhibitor dazoxiben did not reduce platelet aggregate formation while prostacyclin did (Thiemermann & Schror, 1984).…”

Section: General Haemodynamics and Ecgmentioning

confidence: 99%

“…The only study presented so far, in which a thromboxane receptor antagonist was used, failed to demonstrate its beneficial actions on biochemical indices of acute myocardial ischaemia (Burke et al, 1983b). 4-[-(Benzenesulphonamido)-ethyl]-phenoxyacetic acid is a new thromboxane receptor antagonist (Patscheke & Stegmeier, 1984 that has been found in vitro to block vascular and platelet thromboxane receptors at concentrations which did not affect thromboxane biosynthesis (Patscheke & Stegmeier, 1984;Latta et al, 1985). Thus, this compound appeared to be a useful tool to analyse specifically the role ofendogenous thromboxane in the pathophysiology of the developing myocardial infarction.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Treatment of acute myocardial ischaemia with a selective antagonist of thromboxane receptors (BM 13.177)

Schrör

Thiemermann

1986

British J Pharmacology

View full text Add to dashboard Cite

In order to elucidate the role of endogenous thromboxane A2 in myocardial ischaemia, cats were subjected to 5 h of permanent occlusion of the left anterior descending coronary artery (LAD) and treated with the thromboxane receptor antagonist BM 13.177 (5 mg kg−1 h−1, i.v.). In comparison with vehicle‐treated LAD‐occluded cats, BM 13.177 significantly attenuated the loss of creatine phosphokinase‐specific activity from the ischaemic myocardium and antagonized the ischaemia‐induced rise in the ST‐segment of the electrocardiogram. BM 13.177 at the dose used did not reduce plasma thromboxane levels or ischaemia‐induced platelet aggregate formation but considerably antagonized thromboxane‐dependent platelet secretion ex vivo. The study demonstrates some beneficial effects of selective blockade of thromboxane receptors on biochemical and electrophysiological parameters of acute myocardial ischaemia.

show abstract

Section: General Haemodynamics and Ecgmentioning

confidence: 69%

Section: General Haemodynamics and Ecgmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Treatment of acute myocardial ischaemia with a selective antagonist of thromboxane receptors (BM 13.177)

Schrör

Thiemermann

1986

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Leff & Martin (1986) have discussed similar propositions in relation to the characterisation of 5-HT2-like receptors and have raised the question as to whether antagonists chemically related to the natural agonist are of more use in defining subtypes as opposed to antagonists which bear little chemical relation. It is of interest that in our studies, the TP-receptor antagonist which is least prostanoid-like in structure, BM 13177 (Patscheke & Stegmeier, 1984), shows least variation in antagonist affinity. At present it would seem prudent not to subclassify the TP-receptor (TP1-, etc.…”

Section: Compoundsmentioning

confidence: 89%

Heterogeneity of thromboxane A₂ (TP‐) receptors: evidence from antagonist but not agonist potency measurements

Tymkewycz

Jones

Wilson

et al. 1991

British J Pharmacology

View full text Add to dashboard Cite

1 Thromboxane A2 (TP-) receptors in human, rat and rabbit platelets and in smooth muscle of guineapig trachea, rat aorta and rabbit aorta have been characterized by measurement of the potencies of agonists and antagonists having considerable variations in chemical structure. 2 On each washed platelet system, eight prostanoids induced maximal irreversible aggregation (full agonists) and the potency ranking was EP 171 > STA2 > 9,11-azo PGH2 > 9,11-endoxy-lOa-homo PGH2 > U-46619 (standard) > PGH2 = 16-p-fluorophenoxy-co-tetranor PGF2. > 16,16-dimethyl PGF2,. Correlations between the three platelet preparations for both absolute and relative potencies were good. On human platelets, STA2, at concentrations above that required for maximum aggregation, exerted an inhibitory effect which was independent of its interaction with the TP-receptor. 3 Five prostanoids, EP 109, EP 167, EP 204, PTA2 and 16,20-methano PTA2, exhibited partial agonist activity on the platelet and smooth muscle preparations. There was good agreement between absolute potencies on the six preparations; on platelets potency was assessed from shape change measurements, since aggregation, when present, always showed a very shallow concentration-response relationship. The magnitude of the maximum response induced by each compound decreased in the order listed above, to the extent that 16,20-methano PTA2 could be treated as a pure antagonist. 4 With U-46619 as agonist, the pA2 values of seven antagonists were found to be very similar on human and rat platelets. The potency ranking was EP 169 > AH 23848 > EP 092 > ONO 11120 > EP 115 = 16,20-methano PTA2 > BM 13177. There was a similar trend on rabbit platelets but pA2 values were 1.0-1.5 log units smaller; the exception was BM 13177 which had similar affinities. The antagonism produced by EP 169 and AH 23848 was surmountable on rabbit platelets but not on human and rat platelets. 5 None of the antagonists was highly potent on the rabbit aorta (pA2 values < 7.5 by Schild analysis). Affinities on the guinea-pig trachea and the rat aorta were higher and in the same range as those obtained for human and rat platelets. However the correlations of pA2 values between any pair of smooth muscle preparations and between any pair of platelet/smooth muscle preparations were either weak or not significant (P > 0.05). 6 The excellent agreement for both full and partial agonist potencies between the six preparations provides no evidence for TP-receptor subtypes and further suggests that the agonist recognition sites of the TP-receptors could be very similar, if not identical, in nature. In contrast, the different antagonist affinities found in this and other published studies indicate heterogeneity of TP-receptors. However, classification into TP,-, TP2-receptors, etc. on the basis of the limited antagonist data available does not appear appropriate at this time.

show abstract

“…F(ab 0 )2 fragments of a rabbit antihuman VWF antiserum were purchased from American Diagnostics through Biopool (Burlington, Ont.). The thromboxane receptor antagonist, BM13.177 (Patscheke & Stegmeier, 1984) was a generous gift of Dr Stegmeier (Boehringer Mannheim, Germany). Indomethacin and aspirin were purchased from Sigma (St Louis, Mo.…”

Section: Methodsmentioning

confidence: 99%

Platelet activation by a novel solid‐phase agonist: effects of VWF immobilized on polystyrene beads

et al. 1997

View full text Add to dashboard Cite

Summary.The interaction between platelets stirred in suspension and VWF immobilized on polystyrene beads was studied. Platelets aggregated and released ATP in response to stirring with VWF beads. Closer examination of the interaction using transmission electron microscopy revealed that the platelets did not simply aggregate with one another but initially adhered to the beads and spread. Platelets in suspension then bound to the bead-adherent platelets forming layers of platelets associated with each bead. The VWF bead-induced platelet activation was completely inhibited by addition of monoclonal antibody (mAb) to GPIb or GPIIb/IIIa. In addition, the activation response was inhibited in the presence of aspirin, indomethacin or the thromboxane receptor antagonist BM13.177, demonstrating a dependence on an intact cyclo-oxygenase pathway.Platelet function studies were carried out on 30 patients with a history of mild bleeding using conventional optical aggregation and VWF bead-induced platelet activation. 12 patients were abnormal by conventional optical aggregometry, whereas 27 patients showed depressed ATP release in response to VWF beads. The results suggest that easily-bruised patients may have a platelet function defect rather than a vascular-based abnormality and that VWF bead-induced platelet activation is a more sensitive test for detecting platelet dysfunction.

show abstract

Investigations on a selective non-prostanoic thromboxane antagonist, BM 13.177, in human platelets

Cited by 99 publications

References 16 publications

Treatment of acute myocardial ischaemia with a selective antagonist of thromboxane receptors (BM 13.177)

Treatment of acute myocardial ischaemia with a selective antagonist of thromboxane receptors (BM 13.177)

Heterogeneity of thromboxane A₂ (TP‐) receptors: evidence from antagonist but not agonist potency measurements

Platelet activation by a novel solid‐phase agonist: effects of VWF immobilized on polystyrene beads

Contact Info

Product

Resources

About

Investigations on a selective non-prostanoic thromboxane antagonist, BM 13.177, in human platelets

Cited by 99 publications

References 16 publications

Treatment of acute myocardial ischaemia with a selective antagonist of thromboxane receptors (BM 13.177)

Treatment of acute myocardial ischaemia with a selective antagonist of thromboxane receptors (BM 13.177)

Heterogeneity of thromboxane A2 (TP‐) receptors: evidence from antagonist but not agonist potency measurements

Platelet activation by a novel solid‐phase agonist: effects of VWF immobilized on polystyrene beads

Contact Info

Product

Resources

About

Heterogeneity of thromboxane A₂ (TP‐) receptors: evidence from antagonist but not agonist potency measurements