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thromboxane a2

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Description

Thromboxane A2 (TXA2) is a potent vasoconstrictor and platelet aggregator. It is synthesized from arachidonic acid via the cyclooxygenase pathway. TXA2 is produced by platelets and other cells, and its formation is stimulated by various factors, including collagen, thrombin, and ADP. The short half-life of TXA2, only about 30 seconds, limits its action to the immediate vicinity of its synthesis. TXA2 exerts its effects through the activation of the thromboxane receptor (TP), a G protein-coupled receptor. The activation of the TP receptor leads to the activation of downstream signaling pathways, which result in vasoconstriction, platelet aggregation, and bronchoconstriction. TXA2 is a key mediator of hemostasis, the process that stops bleeding. However, excessive TXA2 production can contribute to thrombosis, the formation of blood clots in the arteries. Therefore, TXA2 is a potential target for the development of antithrombotic drugs.'
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Thromboxane A2: An unstable intermediate between the prostaglandin endoperoxides and thromboxane B2. The compound has a bicyclic oxaneoxetane structure. It is a potent inducer of platelet aggregation and causes vasoconstriction. It is the principal component of rabbit aorta contracting substance (RCS). [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

thromboxane A2 : A thromboxane which is produced by activated platelets and has prothrombotic properties: it stimulates activation of new platelets as well as increases platelet aggregation. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID5280497
CHEBI ID15627
SCHEMBL ID34165
MeSH IDM0021438

Synonyms (53)

Synonym
gtpl4482
(z)-7-[(1s,2s,3r,5s)-3-[(e,3s)-3-hydroxyoct-1-enyl]-4,7-dioxabicyclo[3.1.1]heptan-2-yl]hept-5-enoic acid
CHEBI:15627
txa-2
(5z,13e,15s)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dien-1-oic acid
9s,11s-epoxy,15s-hydroxy-thromboxa-5z,13e-dien-1-oic acid
LMFA03030001
5-heptenoic acid, 7-[3-(3-hydroxy-1-octenyl)-2,6-dioxabicyclo[3.1.1]hept-4-yl]-, [1s-[1alpha,3alpha(1e,3r*),4beta(z),5alpha]]-
5-heptenoic acid, 7-[(1s,3r,4s,5s)-3-[(1e,3s)-3-hydroxy-1-octenyl]-2,6-dioxabicyclo[3.1.1]hept-4-yl]-, (5z)-
RCS ,
rabbit aorta contracting substance
cmc_9718
(5z,9alpha,11alpha,13e,15s)-9,11-epoxy-15-hydroxythromboxa-5,13-dien-1-oic acid, [1s-[1alpha,3alpha-(1e,3r*)4beta(z),5alpha]]-7-[3-(3-hydroxy-1-octenyl)-2,6-dioxabicyclo[3.1.1]hept-4-yl]-5-heptenoic a
2,6-dioxabicyclo[3.1.1]heptane, thromboxa-5,13-dien-1-oic acid deriv.
thromboxa-5,13-dien-1-oic acid, 9,11-epoxy-15-hydroxy-, (5z,9alpha,11alpha,13e,15s)-
thromboxane a2
(5z,9alpha,11alpha,13e,15s)-9,11-epoxy-15-hydroxythromboxa-5,13-dien-1-oic acid
(5z,13e)-(15s)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
57576-52-0
C02198
txa2
5-heptenoic acid, 7-(3-(3-hydroxy-1-octenyl)-2,6-dioxabicyclo(3.1.1)hept-4-yl)-, (1s-(1alpha,3alpha,3r*),4beta(z),5alpha)-
benz(a)anthracene-1,7,12(2h)-trione, 3,4-dihydro-3,6,8-trihydroxy-3-methyl-, (-)-
cas_57576-52-0
bdbm82229
unii-4c2a5g825s
4c2a5g825s ,
(5z,9.alpha.,11.alpha.,13e,15s)-9,11-epoxy-15-hydroxythromboxa-5,13-dien-1-oic acid
thromboxane a2 [mi]
5-heptenoic acid, 7-((1s,3r,4s,5s)-3-((1e,3s)-3-hydroxy-1-octen-1-yl)-2,6-dioxabicyclo(3.1.1)hept-4-yl)-, (5z)-
SCHEMBL34165
(5z,9alpha,11alpha,13e,15s)-9,11-epoxy-15-hydroxythromboxa-5,13-dien-1-oate
7-[3-(3-hydroxy-1-octenyl)-2,6-dioxabicyclo[3.1.1]hept-4-yl]-[1s-[1alpha,3alpha(1e,3r*),4beta(z),5alpha]]-5-heptenoic acid
(5z,13e)-(15s)-9a,11a-epoxy-15-hydroxythromboxa-5,13-dienoic acid
(1s-(1alpha,3alpha,3r*),4beta(z),5alpha)-7-(3-(3-hydroxy-1-octenyl)-2,6-dioxabicyclo(3.1.1)hept-4-yl)-5-heptenoate
(5z,13e)-(15s)-9a,11a-epoxy-15-hydroxythromboxa-5,13-dienoate
9s,11s-epoxy,15s-hydroxy-thromboxa-5z,13e-dien-1-oate
(5z)-7-[(1s,3r,4s,5s)-3-[(1e,3s)-3-hydroxy-1-octenyl]-2,6-dioxabicyclo[3.1.1]hept-4-yl]-5-heptenoate
(5z,13e)-(15s)-9alpha,11alpha-epoxy-15-hydroxythromboxa-5,13-dienoic acid
(5z,13e)-(15s)-9,11-epoxy-15-hydroxythromba-5,13-dienoic acid
7-[3-(3-hydroxy-1-octenyl)-2,6-dioxabicyclo[3.1.1]hept-4-yl]-[1s-[1alpha,3alpha(1e,3r*),4beta(z),5alpha]]-5-heptenoate
(5z,9alpha,11alpha,13e,15s)-9,11-epoxy-15-hydroxy-thromboxa-5,13-dien-1-oate
(5z,13e)-(15s)-9-alpha,11-alpha-epoxy-15-hydroxythromboxa-5,13-dienoic acid
(5z,9alpha,11alpha,13e,15s)-9,11-epoxy-15-hydroxy-thromboxa-5,13-dien-1-oic acid
(5z,13e)-(15s)-9,11-epoxy-15-hydroxythromba-5,13-dienoate
(1s-(1alpha,3alpha,3r*),4beta(z),5alpha)-7-(3-(3-hydroxy-1-octenyl)-2,6-dioxabicyclo(3.1.1)hept-4-yl)-5-heptenoic acid
(5z,13e)-(15s)-9-alpha,11-alpha-epoxy-15-hydroxythromboxa-5,13-dienoate
(5z)-7-[(1s,3r,4s,5s)-3-[(1e,3s)-3-hydroxy-1-octenyl]-2,6-dioxabicyclo[3.1.1]hept-4-yl]-5-heptenoic acid
(z)-7-[(1s,3r,4s,5s)-3-[(e,3s)-3-hydroxyoct-1-enyl]-2,6-dioxabicyclo[3.1.1]heptan-4-yl]hept-5-enoic acid
DSNBHJFQCNUKMA-SCKDECHMSA-N
Q774909
DTXSID201317452
AKOS040754197

Research Excerpts

Overview

Thromboxane A2 (TXA2) is a platelet- and cyclooxygenase-derived eicosanoid that has been linked to metastasis. It is thought to be an important mediator of cardiopulmonary dysfunction. stimuli that effect synthesis of this prostanoid are of major interest.

ExcerptReferenceRelevance
"Thromboxane A2 (TXA2) is a platelet- and cyclooxygenase-derived eicosanoid that has been linked to metastasis. "( Urinary Thromboxane B2 and Lethal Prostate Cancer in African American Men.
Ambs, S; Baker, F; Cook, MB; Dorsey, TH; Kiely, M; Loffredo, CA; Milne, GL; Minas, TZ; Smith, CJ; Tang, W; Yates, C, 2022
)
2.16
"Thromboxane A2 (TXA2) is a central prostanoid in the cardiovascular system and is a crucial mediator of vascular homeostasis and platelet aggregation. "( Thromboxane A2 stimulates neurite outgrowth in cerebral cortical neurons via mitogen activated protein kinase signaling.
Muramatsu, R; Sumimoto, S; Yamashita, T, 2015
)
3.3
"Thromboxane A2 (TXA2) is a key mediator of platelet activation and aggregation, and an important mediator of platelet-induced coronary artery constriction. "( Plasma levels of thromboxane A2 on admission are associated with no-reflow after primary percutaneous coronary intervention.
Biasucci, LM; Burzotta, F; Crea, F; Giubilato, S; Leo, A; Leone, AM; Niccoli, G; Porto, I; Pulcinelli, F; Riondino, S; Russo, E; Spaziani, C, 2008
)
2.13
"Thromboxane A2 (TXA2) is a potent lipid mediator released by platelets and inflammatory cells and is capable of inducing vasoconstriction and bronchoconstriction. "( Thromboxane A2 induces airway constriction through an M3 muscarinic acetylcholine receptor-dependent mechanism.
Allen, IC; Coffman, TM; Hartney, JM; Koller, BH; Penn, RB; Wess, J, 2006
)
3.22
"Thromboxane A2 (TXA2) is a positive feedback lipid mediator that is generated upon stimulation of platelets with various agonists. "( P2Y12 receptor-mediated potentiation of thrombin-induced thromboxane A2 generation in platelets occurs through regulation of Erk1/2 activation.
Garcia, A; Kim, S; Kunapuli, SP; Prabhakar, J; Shankar, H, 2006
)
2.02
"Thromboxane A2 is thought to be an important mediator of cardiopulmonary dysfunction, hence stimuli that effect synthesis of this prostanoid are of major interest. "( Ischemia of the limb stimulates thromboxane production and myocardial depression.
Dunham, BM; Hechtman, HB; Huval, WV; Lelcuk, S; Mathieson, MA; Shepro, D; Stemp, LI; Valeri, CR, 1983
)
1.71
"Thromboxane A2 (TxA2) is a vasoconstrictor synthetized by the kidney. "( [Urinary thromboxane B2 in hypertensive patients].
Bariéty, J; Hornych, A; Krief, C; Milliez, P; Safar, M; Simon, A, 1982
)
1.71
"Thromboxane A2 (TXA2) is a potent vasoconstrictor for arterial grafts."( Effect of thromboxane A2 antagonist GR32191B on prostanoid and nonprostanoid receptors in the human internal mammary artery.
He, GW; Yang, CQ, 1995
)
1.41
"Thromboxane A2 is a potent stimulator of platelet aggregation and vasoconstriction and synthesis may be completely inhibited by a single oral dose of 150 mg acetylsalicylic acid or an intravenous dose of 100 mg."( Low dose acetylsalicylic acid in the antithrombotic treatment of patients with stable angina pectoris and acute coronary syndromes (unstable angina pectoris and acute myocardial infarction).
Husted, SE; Vissinger, H; Winther, K, 1994
)
1.01
"Thromboxane A2 (TXA2) is a potent, labile vasoconstrictor which stimulates vessel contraction through vascular smooth muscle TXA2 receptors differing from those in platelets. "( Thromboxane A2 stimulated signal transduction in vascular smooth muscle.
Becker, MW; Dorn, GW, 1993
)
3.17
"Thromboxane A2 (TxA2) is a potent eicosanoid with vasoconstricting and proaggregatory actions."( Associated daily biosynthesis of cortisol and thromboxane A2: a preliminary report.
Cacciafesta, M; Fimognari, FL; Gianni, W; Lama, J; Marigliano, V; Monteleone, G; Paganica, P; Piccirillo, G, 1996
)
1.27
"Thromboxane A2 is a potent vasoconstrictor of pulmonary arteries."( Prostanoid release after lung transplantation.
Gréen, K; Kimblad, PO; Sjöberg, T; Steen, S, 1996
)
1.02
"Thromboxane A2 (TxA2) is a potent vasoconstrictor and has been implicated as a mediator of liver diseases such as ischemic-reperfusion injury. "( Thromboxane A2 analogue contracts predominantly the hepatic veins in isolated canine liver.
Koyama, S; Shibamoto, T; Urayama, H; Wang, HG, 1996
)
3.18
"Thromboxane A2 (TxA2) is a potent vasoconstrictor eicosanoid that has been implicated in the pathogenesis of both human and experimental renal diseases. "( Distribution of binding sites for thromboxane A2 in the mouse kidney.
Coffman, TM; Mannon, PJ; Mannon, RB, 1996
)
2.02
"Thromboxane A2 (TXA2) is a potent vasoconstrictor which is known to be involved in the pathogenesis of experimental glomerulonephritis, although its exact pathogenic significance is not clear in human glomerulonephritis. "( Expression of thromboxane synthase in kidney tissues from patients with IgA nephropathy.
Endoh, M; Kashem, A; Kurokawa, K; Nomoto, Y; Sakai, H; Yamauchi, F; Yano, N, 1997
)
1.74
"Thromboxane A2 (TXA2) is a major arachidonic acid metabolite of platelets and induces platelet functions by binding to specific receptors on the membrane. "( Molecular characterization of a dominantly inherited bleeding disorder with impaired platelet responses to thromboxane A2.
Hirata, T; Kakizuka, A; Narumiya, S; Okuma, M; Ushikubi, F,
)
1.79
"Thromboxane A2 (TXA2) is a potent constrictor of both airway and vascular smooth muscle. "( Different effects of a thromboxane mimetic on blood flow and plasma exudation in guinea pig airways and skeletal muscle.
Cui, ZH; Lötvall, J; Okazawa, A; Skoogh, BE, 1997
)
1.74
"Thromboxane A2 is a biologically potent arachidonate metabolite through the cyclooxygenase pathway. "( Thromboxanes: synthase and receptors.
Shen, RF; Tai, HH, 1998
)
1.74
"Thromboxane A2 (TXA2) is a labile metabolite of arachidonic acid that has potent biological effects. "( Coagulation defects and altered hemodynamic responses in mice lacking receptors for thromboxane A2.
Coffman, TM; Hoffman, M; Koller, BH; Latour, A; Mannon, PJ; Mannon, RB; Oliver, JA; Smithies, O; Thomas, DW, 1998
)
1.97
"Thromboxane A2 is a proaggregative vasoconstrictor that is synthesized and released in reperfusion injury. "( The effects of thromboxane synthase inhibition on reperfusion injury and endothelin-1,2 levels in allograft kidney transplantation in rats.
Aktan, AO; Bilsel, S; Büyükgebiz, O; Dülger, M; Haklar, G, 1999
)
1.75
"Thromboxane A2 is a potent vasoconstrictor for arterial grafts."( Inhibition of vasoconstriction by the thromboxane A2 antagonist GR32191B in the human radial artery.
He, GW; Yang, CQ, 1999
)
1.3
"Thromboxane A2 is an arachidonic acid product, formed by the enzyme cyclooxygenase."( Ifetroban sodium: an effective TxA2/PGH2 receptor antagonist.
Grover, GJ; Rosenfeld, L; Stier, CT, 2001
)
1.03
"Thromboxane A2 (TXA2) is a proaggregatory vasoconstrictor that is synthesized and released during reperfusion of ischaemic brain. "( Correction of ischaemic brain acidosis with SQ29,548/1-benzylimidazole.
Gutierrez, G; Hazle, JD; Ogletree, ML; Pettigrew, LC; Smith, CD, 1992
)
1.73
"Thromboxane A2 (TxA2) is a potent platelet aggregating agent and a necessary intermediate for platelet stimulation by several other platelet agonists. "( Regulation of response to thromboxane A2 in CHRF-288 megakaryocytic cells.
Dorn, GW, 1992
)
2.03
"Thromboxane A2 (TxA2) is a potent vasoconstrictor derived from the metabolism of arachidonic acid. "( U46619, a thromboxane A2 agonist, inhibits KCa channel activity from pig coronary artery.
Scornik, FS; Toro, L, 1992
)
2.13
"Thromboxane A2 is a very unstable arachidonate metabolite, yet a potent stimulator of platelet aggregation and a constrictor of vascular and respiratory smooth muscles. "( Cloning and expression of cDNA for a human thromboxane A2 receptor.
Hayashi, Y; Hirata, M; Kageyama, R; Nakanishi, S; Narumiya, S; Ushikubi, F; Yokota, Y, 1991
)
1.99
"Thromboxane A2 is a potent vasoconstrictor and platelet agonist."( Suppression of thromboxane A2 but not of systemic prostacyclin by controlled-release aspirin.
Clarke, RJ; FitzGerald, GA; Mayo, G; Price, P, 1991
)
1.36
"Thromboxane A2 is a potent bronchial smooth muscle spasmogen in vitro, and it has been implicated in airway inflammation and in the genesis of bronchial hyperresponsiveness in asthma. "( Thromboxane A2 biosynthesis in acute asthma and after antigen challenge.
Barrow, SE; Black, P; Dollery, CT; Fuller, RW; O'Shaughnessy, KM; Taylor, GW; Taylor, IK; Ward, PS, 1991
)
3.17
"Thromboxane A2 (TXA2) is a powerful promoter of platelet aggregation and smooth muscle contraction. "( A stable analogue of thromboxane A2, 9,11-epithio-11,12-methanothromboxane A2, stimulates bone resorption in vitro and osteoclast-like cell formation in mouse marrow culture.
Akatsu, T; Fukuhara, T; Matsumoto, A; Saito, S; Shibasaki, Y; Suda, T; Takahashi, N; Yamada, S; Yamasaki, K, 1991
)
2.04
"Thromboxane A2 (TXA2) is a bioactive metabolite of arachidonic acid which produces vascular smooth muscle contraction and blood platelet aggregation. "( Effects of thromboxane A2 on thoracic aorta of young and old rats: use of selective thromboxane receptor antagonists.
Feller, DR; Miller, DD; Shams, G; Wallace, LJ, 1990
)
2.11
"Thromboxane A2 (TxA2) is a pathogenic factor as it stimulates thrombogenesis and causes vasospastic reactions typical of coronary heart disease. "( [Study of in vitro thromboxane A2 generation by platelets of patients with first-time appearing angina pectoris under the effect of fish diet].
Kalinkina, OM; Perova, NV; Zykova, VP, 1990
)
2.05
"Thromboxane A2 (TxA2) is a potent platelet agonist that serves as an amplifying signal after exposure of platelets to other stimulants, such as thrombin, in vitro. "( Regulation of thromboxane receptor activation in human platelets.
FitzGerald, GA; Murray, R, 1989
)
1.72
"Thromboxane A2 (TxA2) is an arachidonic acid metabolite which causes severe pulmonary vasoconstriction (PV) and may mediate the PV produced by platelet-activating factor (PAF-acether) and leukotriene D4 (LTD4). "( Influence of thromboxane A2 receptor antagonism on pulmonary vasoconstrictor responses.
Bradley, LM; Czaja, JF; Goldstein, RE; Stambouly, JJ, 1989
)
2.09
"Thromboxane A2 (TxA2) is a potent platelet aggregator as well as a vascular and bronchial constrictor. "( [Effects of thromboxane A2 synthetase inhibitor, DP-1904 on the action of vasoactive substances in rabbit blood vessel smooth muscle preparations].
Iwanaga, T; Kitamura, S; Kobayashi, J; Kuratomi, Y; Shimizu, K, 1989
)
2.1
"Thromboxane A2 is a known inducer of platelet aggregation probably through the exposure of platelet fibrinogen receptors."( Nephrotic syndrome: a platelet hyperaggregability state.
Feldman, BF; Rasedee, A, 1985
)
0.99
"Thromboxane A2 is a prostanoid having potent platelet aggregatory and vasoconstrictor properties. "( Thromboxane A2 in severe hypertension and stroke in stroke-prone spontaneously hypertensive rats.
Benter, IF; Levine, S; Stier, CT, 1988
)
3.16
"Thromboxane A2 synthase is a cytochrome P450-type enzyme and its interaction with imidazole or pyridine-based inhibitors could be studied by absolute and difference spectroscopy with the solubilized as well as the purified enzyme. "( Spectral studies on structure-activity relationships of thromboxane synthase inhibitors.
Haurand, M; Hecker, M; Terao, S; Ullrich, V, 1986
)
1.71

Effects

Thromboxane A2 (TxA2) has been implicated in the pathogenesis of airway hyperresponsiveness. Thromboxanes A2 has not been reported to date as a physiological stimulant of Cl- secretion in the distal colon.

ExcerptReferenceRelevance
"Thromboxane A2 has a very short half life and has neither been isolated nor synthesized."( Vasoconstrictor response of arterioles of the hamster cheek pouch to norepinephrine, prostaglandin H2, F2 alpha and carbocyclic thromboxane A2, a possible thromboxane A2 analogue.
Herrmann, KS, 1982
)
1.19
"The thromboxane A2 receptor (TP) has been implicated in restenosis after vascular injury, which induces vascular smooth muscle cell (VSMC) migration and proliferation. "( Thromboxane A2 Activates YAP/TAZ Protein to Induce Vascular Smooth Muscle Cell Proliferation and Migration.
Feng, X; Guan, KL; Li, FL; Li, MT; Liu, P; Meng, Z; Sun, YP; Wang, Z; Xiong, Y; Yu, Y; Yuan, HX; Zhou, X, 2016
)
2.44
"Thromboxane A2 (TXA2) has been suggested to play a significant role in the development of portal hypertension in fibrosis, and Kupffer cell (KC) derived TXA2 has been shown to mediate the hyperresponsiveness of the portal circulation to the vasoconstrictive actions of endothelin-1 (ET-1) during endotoxemia. "( LPS exacerbates endothelin-1 induced activation of cytosolic phospholipase A2 and thromboxane A2 production from Kupffer cells of the prefibrotic rat liver.
Klaus, C; Masrorpour, M; Miller, AM; Zhang, JX, 2007
)
2.01
"Thromboxane A2 has been proposed as an ionophore capable to transport calcium from the platelet dense tubular system to the cytoplasm to activate the contractile proteins. "( Evidence of a thromboxane A2-Ca2+ complex: a conformational approach.
Brasseur, R; Ruysschaert, JM, 1984
)
2.07
"Thromboxane A2 has a very short half life and has neither been isolated nor synthesized."( Vasoconstrictor response of arterioles of the hamster cheek pouch to norepinephrine, prostaglandin H2, F2 alpha and carbocyclic thromboxane A2, a possible thromboxane A2 analogue.
Herrmann, KS, 1982
)
1.19
"Thromboxane A2 (TxA2) has been implicated in the pathogenesis of airway hyperresponsiveness. "( U46619-induced bronchoconstriction in asthmatic subjects is mediated by acetylcholine release.
Inman, MD; O'Byrne, PM; Saroea, HG, 1995
)
1.73
"Thromboxane A2 (TXA2) has been implicated in the pathogenesis of progressive glomerulosclerosis and stimulates the synthesis of matrix protein by mesangial cells (MCs). "( Role for transforming growth factor beta in thromboxane-induced increases in mesangial cell fibronectin synthesis.
Craven, PA; DeRubertis, FR; Negrete, H; Studer, RK, 1995
)
1.73
"Thromboxane A2 has the opposite effect of prostaglandins."( Protective effect of the thromboxane A2 receptor antagonist ONO 3708 on ischemia-reperfusion injury in the dog liver.
Haba, Y; Hanazaki, K; Iida, F; Kajikawa, S; Kuroda, T; Shiohara, E, 1994
)
1.31
"Thromboxane A2 (TXA2) has been implicated as an important mediator of cardiovascular diseases. "( Testosterone treatment enhances thromboxane A2 mimetic induced coronary artery vasoconstriction in guinea pigs.
Halushka, PV; Masuda, A; Mathur, RS; Matsuda, K; Morinelli, TA; Schrör, K, 1994
)
2.01
"Thromboxane A2 has been found to be a central mediator in the development of septic and oleic acid (OA)-induced acute lung injury."( Postinjury thromboxane receptor blockade ameliorates acute lung injury.
Cephas, GA; Corbin, RS; Frierson, HF; Goff, CD; Kron, IL; Theiss, SD; Tribble, CG; Young, JS, 1997
)
1.02
"Thromboxane A2 (TXA2) has not been reported to date as a physiological stimulant of Cl- secretion in the distal colon."( Thromboxane A2, released by the anti-tumour drug irinotecan, is a novel stimulator of Cl- secretion in isolated rat colon.
Hamada, N; Ikari, A; Kakinoki, B; Sakai, H; Sato, T; Takeguchi, N; Yasue, M, 1997
)
2.46
"Thromboxane A2 (TxA2) has been implicated in a number of processes in normal kidney physiology and as a mechanism for injury in renal disease. "( A genetic approach for studying the role of thromboxane A2 in the kidney.
Coffman, TM; Thomas, DW, 1998
)
2
"Thromboxane A2 (TXA2) has been believed to have a key role in atherosclerogenesis and post-angioplasty restenosis."( Downregulation of nitric oxide accumulation by cyclooxygenase-2 induction and thromboxane A2 production in interleukin-1beta-stimulated rat aortic smooth muscle cells.
Fujino, T; Kawabe, J; Kikuchi, K; Ohsaki, Y; Shiokoshi, T, 2002
)
1.26
"Thromboxane A2 (TxA2) has either no effect or may cause a slight relaxation of the sphincter."( The high yield of prostacyclin biosynthesis by the iris and its effects on the intraocular muscles.
de Deckere, EA; Dutilh, CE; van Alphen, GW, 1978
)
0.98
"Thromboxane A2 (TxA2) has been implicated in airway responses to allergen and in the bronchial hyperresponsiveness observed in asthma. "( A thromboxane mimetic, U-46619, produces plasma exudation in airways of the guinea pig.
Barnes, PJ; Chung, KF; Elwood, W; Lötvall, J; Sakamoto, T; Tokuyama, K, 1992
)
1.73
"Thromboxane A2 has opposite effects."( Renin-angiotensin-aldosterone system and thromboxane A2/prostacyclin in normotensive and hypertensive black Zimbabweans.
Mufunda, JJ; Somova, LI, 1992
)
1.27
"Thromboxane A2(TxA2) has been implicated in the pathogenesis of airway hyperresponsiveness. "( Effect of an inhaled thromboxane mimetic (U46619) on airway function in human subjects.
Jones, GL; O'Byrne, PM; Saroea, HG; Watson, RM, 1992
)
1.73
"Thromboxane A2 (TXA2) has been suggested to play an important role in the pathogenesis of bronchial asthma. "( [Bronchial hyperresponsiveness to histamine induced by intravenous administration of thromboxane A2 (TXA2) in guinea-pigs].
Kurosawa, M; Tsukagoshi, H, 1991
)
1.95
"A thromboxane A2 receptor has been identified using receptor antagonists and photoaffinity labels."( Platelet receptors.
Colman, RW, 1990
)
0.84
"Thromboxane A2 (TxA2) has been implicated as a mediator of renal and cardiovascular diseases. "( Thromboxane A2 and prostaglandin endoperoxide analogue effects on porcine renal blood flow.
Cirino, M; Ford-Hutchinson, AW; Hadden, J; MacDonald, C; Morton, H, 1990
)
3.16
"Thromboxane A2 (TXA2) has been reported to be increased in the hydronephrotic kidney, and the present study was undertaken to investigate whether TXA2 might be responsible for these findings."( Effect of thromboxane inhibition on tubuloglomerular feedback in hydronephrotic kidneys.
Morsing, P; Persson, AE; Stenberg, A, 1989
)
1
"Thromboxane A2 has been implicated as a mediator of cardiorespiratory dysfunction in sepsis. "( Thromboxane A2 mediates hemodynamic and respiratory dysfunction in graded bacteremia.
Gann, DS; Handy, JR; Hulstyn, M; Husain, SE; Slotman, GJ; Yellin, SA, 1986
)
3.16

Actions

Thromboxane A2 (TXA2) promotes ischemic stroke injury and has strong effects in vascular contraction and vascular endothelial cell dysfunction. Thromboxene A2 plays a major role in the ischemia-reperfusion injury of acute compartmental syndrome.

ExcerptReferenceRelevance
"Thromboxane A2 (TXA2) promotes ischemic stroke injury and has strong effects in vascular contraction and vascular endothelial cell dysfunction. "( N2 ameliorates neural injury during experimental ischemic stroke via the regulation of thromboxane A2 production.
Chu, S; Fan, W; Fang, W; He, G; He, W; Huang, J; Li, Y; Wu, Q; Zhou, Y, 2014
)
2.07
"Thromboxane A2 plays a major role in the ischemia-reperfusion injury of acute compartmental syndrome. "( Thromboxane A2 in postischemic acute compartmental syndrome.
Dabby, D; Dekel, S; Greif, F; Lelcuk, S; Rubin, M; Yaniv, M, 1998
)
3.19
"Thromboxane A2 (TxA2) plays an important role in asthma. "( [Thromboxane A2 synthase inhibitor and receptor antagonist].
Adachi, M; Minoguchi, K, 2001
)
2.66
"Thromboxane A2 plays an important role in the early pulmonary hypertension in sepsis; however, the role of thromboxane A2 later in sepsis is unclear."( Delayed thromboxane synthesis inhibition, but not cholinergic blockade, reverses group B streptococcus-induced pulmonary hypertension.
Gray, BM; Li, JX; Lu, CY; Oliver, JR; Philips, JB, 1992
)
1

Treatment

ExcerptReferenceRelevance
"Pretreatment with thromboxane A2 synthetase inhibitors markedly improved the survival rates."( Protective effects of thromboxane A2 synthetase inhibitors on endotoxin shock.
Fukumoto, S; Tanaka, K, 1983
)
0.9

Toxicity

ExcerptReferenceRelevance
" However, there are several possible adverse effects of NSAIDs."( Potential renal, haematological and allergic adverse effects associated with nonsteroidal anti-inflammatory drugs.
Kenny, GN, 1992
)
0.28
" gondii ratios as low as 1:3 were toxic to the organisms with direct cell-cell contact essential for platelet-mediated cytotoxicity."( Human platelet-mediated cytotoxicity against Toxoplasma gondii: role of thromboxane.
Chi, EY; Fritsche, TR; Henderson, WR; Yong, EC, 1991
)
0.28
" In CyA toxic rats, renal dysfunction can be partially reversed by inhibitors of thromboxane synthase."( Thromboxane receptor blockade improves cyclosporine nephrotoxicity in rats.
Coffman, T; Collins, D; Klotman, PE; Mayros, SD; Ruiz, P; Spurney, RF, 1990
)
0.28
" Indomethacin alone had no adverse effect on glomerular function; however, when coadministered with CsA an exaggerated decrease in renal function was observed."( Modulation of experimental cyclosporine nephrotoxicity by inhibition of thromboxane synthesis.
Freeman, D; Keown, P; McDonald, J; Petric, R; Stiller, C; Wallace, C, 1990
)
0.28
"The main adverse effect of cyclosporine A (CyA) is nephrotoxicity."( Cyclosporine A nephrotoxicity: role of thromboxane and reactive oxygen species.
Arribas, I; de Arriba, G; Parra, T; Perez de Lema, G; Rodriguez-Puyol, D; Rodriguez-Puyol, M, 1998
)
0.3

Pharmacokinetics

ExcerptReferenceRelevance
"A selective thromboxane A2 (TXA2) receptor blocking agent, vapiprost, was orally administered to healthy male Japanese volunteers to investigate the pharmacokinetic and pharmacodynamic properties."( Pharmacokinetic and pharmacodynamic profiles of vapiprost, a selective, long-lasting thromboxane receptor antagonist, after single and multiple oral administration to healthy volunteers.
Hirano, K; Mizuno, A; Nagashima, S; Nakashima, M; Uematsu, T, 1991
)
0.66
" Pharmacodynamic effects were measured ex vivo by the testing of platelet functions such as shape change, aggregation, and [3H]serotonin release."( The pharmacokinetic and pharmacodynamic profiles of the thromboxane A-2 receptor blocker BM 13.177.
Endele, R; Kaufmann, B; Neugebauer, G; Patscheke, H; Staiger, C; Stegmeier, K; Strein, K, 1986
)
0.27
" The formulation and route of administration profoundly influenced several pharmacokinetic parameters for aspirin: the maximum concentration (Cmax, ng."( Pharmacokinetics of low-dose oral modified release, soluble and intravenous aspirin in man, and effects on platelet function.
Bochner, F; Lloyd, JV; Morris, PM; Siebert, DM; Williams, DB, 1988
)
0.27
" Population pharmacokinetic analysis with NONMEM showed plasma concentration-time profiles of AA-2414 to be best characterized by a two-compartment open model with zero-order input and first-order elimination."( Characterization of the pharmacokinetics and pharmacodynamics of a new oral thromboxane A2-receptor antagonist AA-2414 in normal subjects: population analysis.
Granneman, GR; Hussein, Z; Locke, CS; Orchard, MA; Ringham, GL; Samara, E, 1994
)
0.52
" In the single-dose study (200, 300, 400 mg), the area under the plasma concentration-time curve (AUC) and the maximum plasma concentration (Cmax) increased non-linearly with dose, while the mean elimination half-life (V0) was essentially unchanged (3."( Pharmacokinetic and pharmacodynamic properties of FK070 (KDI-792), a novel thromboxane receptor antagonist/thromboxane synthetase inhibitor, after single and multiple oral administrations to healthy volunteers.
Kosuge, K; Nakano, M; Nakashima, M; Terakawa, M; Uematsu, T; Umemura, K, 1996
)
0.29
"kg-1, whereas in Cmax an over-proportional increase was observed."( Pharmacokinetics and metabolism of the new thromboxane A2 receptor antagonist ramatroban in animals. 1st communication: absorption, concentrations in plasma, metabolism, and excretion after single administration to rats and dogs.
Ahr, HJ; Beckermann, B; Boberg, M; Bühner, K; Hirayama, M; Siefert, HM; Steinke, W; Wünsche, C, 1997
)
0.56
"Terbogrel is a potent agent having two distinct, complimentary pharmacodynamic actions, namely inhibition of thromboxane synthase and antagonism of the TxA2 receptor."( Pharmacokinetics and pharmacodynamics of terbogrel, a combined thromboxane A2 receptor and synthase inhibitor, in healthy subjects.
Guth, BD; Narjes, H; Nehmiz, G; Riedel, A; Schubert, HD; Tanswell, P, 2004
)
0.56
"19 L/kg) and the elimination half-life was short (2."( Pharmacokinetics and pharmacodynamics of meloxicam in piglets.
Fosse, TK; Haga, HA; Haugejorden, G; Hormazabal, V; Horsberg, TE; Ranheim, B, 2008
)
0.35
" The improvement of our understanding on the pharmacokinetic and pharmacodynamic characteristics of these drugs enables the tailoring of the most appropriate anti-thrombotic therapy to the individual patient and risk situation in the daily clinical practice."( Pharmacodynamic properties of antiplatelet agents: current knowledge and future perspectives.
Goudevenos, IA; Kalantzi, KI; Tselepis, AD; Tsoumani, ME, 2012
)
0.38

Compound-Compound Interactions

ExcerptReferenceRelevance
" This study reveals 1) a differential efficacy of TXA2 synthase inhibition, singly or combined with TXA2/prostaglandin endoperoxide receptor antagonism, depending on the extent of the vessel wall lesion triggering thrombosis and the size of the thrombus required to obstruct the vascular lumen and 2) a significant synergism in preventing occlusive thrombosis of extensively damaged coronary arteries between strong TXA2 synthase inhibition and comparatively modest TXA2/prostaglandin endoperoxide receptor antagonism with ridogrel."( Differential effects of thromboxane A2 synthase inhibition, singly or combined with thromboxane A2/prostaglandin endoperoxide receptor antagonism, on occlusive thrombosis elicited by endothelial cell injury or by deep vascular damage in canine coronary ar
De Clerck, F; Hemans, C; Van Ammel, K; Van de Water, A; Vandeplassche, G; Wouters, L; Xhonneux, R, 1991
)
0.59
"Differential effects on human platelet function of thromboxane A2 (TXA2) synthetase inhibition singly and of TXA2 synthetase inhibition combined with TXA2/prostaglandin endoperoxide receptor antagonism were revealed, using ridogrel as a probe."( Effect of thromboxane A2 synthetase inhibition, singly and combined with thromboxane A2/prostaglandin endoperoxide receptor antagonism, on inositol phospholipid turnover and on 5-HT release by washed human platelets.
de Chaffoy de Courcelles, D; De Clerck, F, 1990
)
0.93
"To research effects of Radix Astragali total saponin combined with Radix Paeoniae Rubra glucosides (double glucosides of Qi-Shao, DGQS) on antiplatelet."( [Study on antiplatelet effect of radix astragali total saponin combined with Radix paeoniae rubra glucosides].
Gao, J; Liu, Q; Peng, D; Xia, L; Xu, X, 2002
)
0.31
"To explore the interaction of low-dosage aspirin combined with angiotensin-converting enzyme (ACE) inhibitors by prostacyclin (PGI2), thromboxone A2 (TXA2) and norepinephrine (NE)) levels in rabbits' blood."( [Effect of low-dosage aspirin combined with perindopril on prostacyclin, thromboxone A2, and norepinephrine in rabbits' blood].
Fang, YX; Li, J; Zhuang, HP, 2002
)
0.31
" The ratio of PGI2 to TXA2 increased, and NE levels decreased significantly during the administration of aspirin combined with ACE inhibitors."( [Effect of low-dosage aspirin combined with perindopril on prostacyclin, thromboxone A2, and norepinephrine in rabbits' blood].
Fang, YX; Li, J; Zhuang, HP, 2002
)
0.31
"To explore the interactive effect of low-dosage aspirin (ASA) combined with perindopril (PER), on prostacyclin (PGI2), thromboxone A2 (TXA2), and norepinephrine (NE) in the blood of arteriosclerosis rabbit models and the cardiac function."( [Effect of aspirin combined with perindopril on prostacyclin, thromboxone A2, and norepinephrine in the blood of arteriosclerosis rabbit models and the cardiac function].
Li, J; Liu, LH; Zhuang, HP, 2003
)
0.32
"The ratio of PGI2 to TXA2 increased, and the NE levels decreased significantly; meanwhile, the heart rate decreased and the cardiac function improved during the administration of aspirin combined with perindopril in arteriosclerosis rabbit models."( [Effect of aspirin combined with perindopril on prostacyclin, thromboxone A2, and norepinephrine in the blood of arteriosclerosis rabbit models and the cardiac function].
Li, J; Liu, LH; Zhuang, HP, 2003
)
0.32
" Thus, combination with a TP antagonist might reveal an antiinflammatory effect of a COX-2 inhibitor in this disease."( Cyclooxygenases, thromboxane, and atherosclerosis: plaque destabilization by cyclooxygenase-2 inhibition combined with thromboxane receptor antagonism.
Egan, KM; FitzGerald, GA; Fries, S; Lawson, JA; Lucitt, MB; Puré, E; Wang, M; Zukas, AM, 2005
)
0.33
" Combination with the COX-2 inhibitor failed to augment the impact of TP antagonism alone on lesion area."( Cyclooxygenases, thromboxane, and atherosclerosis: plaque destabilization by cyclooxygenase-2 inhibition combined with thromboxane receptor antagonism.
Egan, KM; FitzGerald, GA; Fries, S; Lawson, JA; Lucitt, MB; Puré, E; Wang, M; Zukas, AM, 2005
)
0.33
" Despite early intervention, selective inhibition of COX-2, alone or in combination with a TP antagonist, failed to modify disease progression but may undermine plaque stability when combined with the antagonist."( Cyclooxygenases, thromboxane, and atherosclerosis: plaque destabilization by cyclooxygenase-2 inhibition combined with thromboxane receptor antagonism.
Egan, KM; FitzGerald, GA; Fries, S; Lawson, JA; Lucitt, MB; Puré, E; Wang, M; Zukas, AM, 2005
)
0.33

Bioavailability

The early pulse of rarefaction developed before a loss of NO bioavailability and was associated with altered venular function. Vascular reactivity and biochemical analyses demonstrated that even mild elevations in PVD risk severely attenuated nitric oxide (NO) bioavailability, increasing thromboxane A2 levels.

ExcerptReferenceRelevance
" The bioavailability of plain ASA after oral administration amounts to 40-50% at therapeutic doses."( [Clinical pharmacology of acetylsalicylic acid].
Schröder, H; Schrör, K, 1992
)
0.28
"5 mg daily or as 325 mg on alternate days, despite the minimal systemic bioavailability of controlled-release aspirin."( Suppression of thromboxane A2 but not of systemic prostacyclin by controlled-release aspirin.
Clarke, RJ; FitzGerald, GA; Mayo, G; Price, P, 1991
)
0.63
" The present study was designed to investigate whether the abnormally prolonged post-ASA BT in uremia is due to different ASA pharmacokinetics and bioavailability that might be a consequence of uremic condition, platelet cyclooxygenase is peculiarly sensitive to ASA in uremia, and ASA affects primary hemostasis in uremia by a mechanism independent of cyclooxygenase inhibition."( Aspirin prolongs bleeding time in uremia by a mechanism distinct from platelet cyclooxygenase inhibition.
Bonati, M; Gaspari, F; Livio, M; Orisio, S; Remuzzi, G; Viganò, G, 1987
)
0.27
" We have demonstrated that a 50 mg enteric-coated aspirin formulation (Astrix) which has an absorption rate much lower than soluble aspirin, is sufficient to inhibit platelet thromboxane synthesis while causing no major decrease in vascular prostacyclin synthesis."( Effect of 50 mg enteric-coated aspirin (Astrix) on thromboxane and prostacyclin synthesis.
Foreman, RK; James, MJ; Walsh, JA, 1987
)
0.27
" The oral bioavailability of ramatroban was complete in the dog but amounted to about 50% in the rat due to presystemic elimination."( Pharmacokinetics and metabolism of the new thromboxane A2 receptor antagonist ramatroban in animals. 1st communication: absorption, concentrations in plasma, metabolism, and excretion after single administration to rats and dogs.
Ahr, HJ; Beckermann, B; Boberg, M; Bühner, K; Hirayama, M; Siefert, HM; Steinke, W; Wünsche, C, 1997
)
0.56
"These studies support the notion that (i) products of lipid oxidation may reduce NO bioactivity without affecting endothelial NO synthase mass or catalytic activity, (ii) the mechanisms involved in the endothelial dysfunction induced by hypercholesterolaemia and oxidized lipids may differ among vascular beds, and (iii) decreased NO bioavailability does not necessarily result in systemic hypertension, but it may enhance the sensitivity to the hypertensinogenic effect of dietary salt."( Relationship between hypercholesterolaemia, endothelial dysfunction and hypertension.
Hayakawa, H; Raij, L, 1999
)
0.3
" The bioavailability of aspirin (based on salicylate concentrations) from the controlled-release formulation was approximately 90% relative to the solution, and drug release was not affected by co-administration of a standard breakfast."( Biopharmaceutical characterisation of a low-dose (75 mg) controlled-release aspirin formulation.
Charman, SA; Charman, WN; Fitzgerald, GA; Frisbee, SE; Lockhart, EA; Monkhouse, DC; Weisman, S, 1993
)
0.29
"The bioavailability (BA) of ramatroban was estimated at 21."( Pharmacokinetic analysis of ramatroban using a recirculatory model with enterohepatic circulation by measuring portal and systemic blood concentration difference in Sprague-Dawley and Eisai hyperbilirubinemic rats.
Moriwaki, T; Yamamoto, A; Yasui, H, 2004
)
0.32
"NO targets activation-dependent adhesion mediated by alpha(2)beta(1), possibly by reducing bioavailability of platelet-derived ADP, but has no effect on activation-independent adhesion mediated by GPVI."( Nitric oxide specifically inhibits integrin-mediated platelet adhesion and spreading on collagen.
Farndale, RW; Homer-Vanniasinkam, S; Naseem, KM; Riba, R; Roberts, W, 2008
)
0.35
" Such effects of ginsenosides including cardioprotective and anti-platelet activities have shown stability and bioavailability limitations."( Ginsenoside-Rp1 inhibits platelet activation and thrombus formation via impaired glycoprotein VI signalling pathway, tyrosine phosphorylation and MAPK activation.
Cho, JY; Endale, M; Kamruzzaman, SM; Kim, SD; Lee, WM; Park, HJ; Park, JY; Park, MH; Park, TY; Rhee, MH, 2012
)
0.38
" Moreover, we evaluated endothelial function by dose-relaxation curves to acetylcholine, hepatic NO bioavailability and TXA2 production."( Resveratrol improves intrahepatic endothelial dysfunction and reduces hepatic fibrosis and portal pressure in cirrhotic rats.
Bosch, J; Di Pascoli, M; Diví, M; García-Pagán, JC; Gracia-Sancho, J; Rodríguez-Vilarrupla, A; Rosado, E; Vilaseca, M, 2013
)
0.39
" Although the total extent of rarefaction was well predicted by the loss in NO bioavailability, the early pulse of rarefaction developed before a loss of NO bioavailability and was associated with altered venular function (increased leukocyte adhesion/rolling), and early elevation in oxidant stress, TNF-α levels, and the vascular production of thromboxane A2 (TxA2)."( Distinct temporal phases of microvascular rarefaction in skeletal muscle of obese Zucker rats.
Brock, RW; Butcher, JT; Chantler, PD; DeVallance, ER; Frisbee, JC; Frisbee, SJ; Goodwill, AG; Olfert, IM, 2014
)
0.57
" Vascular reactivity and biochemical analyses demonstrated that even mild elevations in PVD risk severely attenuated nitric oxide (NO) bioavailability and caused progressive shifts in arachidonic acid metabolism, increasing thromboxane A2 levels."( Increased peripheral vascular disease risk progressively constrains perfusion adaptability in the skeletal muscle microcirculation.
Brock, RW; Brooks, SD; Butcher, JT; Chantler, PD; d'Audiffret, AC; Frisbee, JC; Frisbee, SJ; Goodwill, AG; Lombard, JH; Olfert, IM; Shrader, CD; Stapleton, PA; Tabone, LE, 2016
)
0.62
" NO bioavailability in response to U46619 was suppressed by estrogen withdrawn in young and senescent mice and was restored by the administration of estradiol."( Decreased bioavailability of nitric oxide in aorta from ovariectomized senescent mice. Role of cyclooxygenase.
Dantas, AP; Garabito, M; Hermenegildo, C; Medina, P; Novella, S; Pérez-Monzó, I; Segarra, G; Vidal-Gómez, X, 2016
)
0.43

Dosage Studied

The synthesis of thromboxane A2 (measured as TXB2) by blood platelets in the presence of ethanol and in platelets from animals dosed chronically with ethanol has been examined. Preincubation of rat aorta with 10 microM SQ 29,548, a "selective" antagonist ofThromboxanes A2/prostaglandin H2 (TP) receptors, caused a rightward shift in the dose-response curve.

ExcerptRelevanceReference
"The synthesis of thromboxane A2 (measured as TXB2) by blood platelets in the presence of ethanol and in platelets from animals dosed chronically with ethanol has been examined."( The effect of ethanol on thromboxane synthesis by blood platelets.
Pennington, SN; Smith, CP, 1979
)
0.6
" Dose-response curves for U-46619 and U-44069 were shifted to the right in a parallel manner, and daltroban had no significant effect on responses to norepinephrine, serotonin, angiotensin II, BAY K 8644, endothelin-(ET) 1, ET-2, or platelet-activating factor (PAF)."( Daltroban blocks thromboxane responses in the pulmonary vascular bed of the cat.
Babycos, CR; Hood, JS; Ibrahim, IN; Kadowitz, PJ; McMahon, TJ; Nossaman, BD, 1992
)
0.28
" While pretreatment with inhaled AS-35 (1mg) did not affect the STA2 dose-response curve."( Interaction of thromboxane A2 and leukotrienes in guinea pig airways in vivo.
Bando, T; Fujimura, M; Matsuda, T; Mizuhashi, K, 1991
)
0.63
"Arachidonic acid (AA)- or thromboxane A2/prostaglandin H2 (TXA2/PGH2) analog (STA2 and U-46619)-induced aggregations yielded a bell-shaped dose-response curve."( Elevation of platelet cyclic AMP level by thromboxane A2/prostaglandin H2 receptor agonists.
Ishikawa, Y; Ogawa, A, 1991
)
0.85
"1 mg/kg/hr for daltroban; these dosing rates are associated with significant alterations in eicosanoid-related pharmacologic effects."( Evaluation of a prostacyclin analog, iloprost, and a thromboxane A2 receptor antagonist, daltroban, in experimental intimal hyperplasia.
Bjornsson, TD; Dryjski, M; Levitt, MA; Tluczek, J, 1991
)
0.53
" Tachyphylaxis was not noted in 5 control pigs given sequential repeats of the PAF dosing series."( In vivo enhancement of platelet activating factor-induced prostacyclin production by OKY-046, a selective inhibitor of thromboxane A2 synthase.
Davenport, NJ; Feuerstein, GZ; Goldstein, RE, 1991
)
0.49
"35 mg/animal) significantly reduced the airway responses produced by inhalation of leukotriene C4 and STA2, in a dose-dependent manner, while the pretreatment did not affect the histamine dose-response curve."( Inhibitory effect of inhalation of a thromboxane synthetase inhibitor on bronchoconstriction induced by aerosolized leukotriene C4 and thromboxane A2 analogue in anesthetized guinea pigs.
Fujimura, M; Matsuda, T; Miyake, Y; Ogawa, H; Saito, M; Sakamoto, S, 1991
)
0.48
" Following the administration of SQ 29,548, pressor responses to both U44069 and U46619 were reduced significantly, and the dose-response curves for both TXA2 mimics were shifted to the right in a parallel fashion."( Influence of SQ 29,548 on vasoconstrictor responses in the hindquarters vascular bed of the cat.
Bellan, JA; Kadowitz, PJ; McMahon, TJ; McNamara, DB; Minkes, RK, 1991
)
0.28
" SQ 30741 had no significant effect on mean vascular pressures in the cat, and the dose-response curve for U-46619 was shifted to the right in a parallel manner with a similar apparent maximal response."( Influence of SQ 30741 on thromboxane receptor-mediated responses in the feline pulmonary vascular bed.
Feng, CJ; Hood, JS; Ibrahim, IN; Kadowitz, PJ; McMahon, TJ; Nossaman, BD, 1991
)
0.28
"Maximal inhibition of platelet thromboxane A2 production was sustained during long-term dosing with controlled-release aspirin, whereas basal prostacyclin biosynthesis fell only slightly and systemic synthesis of prostacyclin stimulated by bradykinin was preserved."( Suppression of thromboxane A2 but not of systemic prostacyclin by controlled-release aspirin.
Clarke, RJ; FitzGerald, GA; Mayo, G; Price, P, 1991
)
0.92
" We found 1) that the two responses to activin A/EDF were distinctly affected by the initial cell density; 2) that the dose-response curves for activin A/EDF were similar (ED50 = approximately 100 pM), whereas the time course of induction of TXA2 synthetic activity was much faster; and 3) that other erythroid differentiation inducers of MEL cells, namely dimethyl sulfoxide and hexamethylene bisacetamide, had little or no effect on TXA2 synthesis."( Activin A/erythroid differentiation factor induces thromboxane A2 synthetic activity in murine erythroleukemia cells.
Ogata, E; Shimizu, T; Yamashita, T, 1991
)
0.53
"The pharmacokinetics and pharmacodynamics of biochemical effect of a selective thromboxane synthase inhibitor, CGS 12970, were studied in healthy male volunteers after a dosing scheme of either 200 mg once daily or 100 mg twice a day for 6 days."( Pharmacokinetics of CGS 12970 and inhibition of thromboxane synthesis after oral administration in healthy adults.
Douglas, FL; Linberg, L; Martin, LL; Piraino, A; Rakhit, A; Schaffer, AV; Singh, K, 1991
)
0.28
"Using the hamster cheek pouch preparation and intravital microscopy and fluorometry methods, we quantitated the dose-response effects of topically applied platelet-activating factor (PAF) on microvascular permeability, vessel diameter and leukocyte adhesion and investigated the biochemical pathways of this compound."( Acute microcirculatory effects of platelet-activating factor.
Dillon, PK; Durán, WN, 1990
)
0.28
" Multiple dosing with GR32191, 17."( Preliminary assessment of a novel thromboxane A2 receptor-blocking drug, GR32191, in healthy subjects.
Lumley, P; Thomas, M, 1990
)
0.56
" Since none of the compounds tested produced a sustained inhibition of TXA2 synthesis, the disappointing clinical results with this class of drugs may be due to an incomplete blockade of thromboxane synthase with the dosage regimens used."( Preliminary clinical studies with thromboxane synthase inhibitors and thromboxane receptor blockers. A review.
Fiddler, GI; Lumley, P, 1990
)
0.28
" Preincubation of rat aorta with 10 microM SQ 29,548, a "selective" antagonist of thromboxane A2/prostaglandin H2 (TP) receptors, caused a rightward shift in the dose-response curve and a reduction in the maximal response to endothelin-1."( Role of thromboxane A2/prostaglandin H2 receptor in the vasoconstrictor response of rat aorta to endothelin.
Mok, LL; Reynolds, EE, 1990
)
0.94
"1-fold (n = 3) shift to the right in the U-46,619 dose-response for renal vasoconstriction."( Activity of the short-acting thromboxane receptor antagonist, SQ 30,741, in thrombolytic and vasospastic models in monkeys.
Hartl, KS; Heran, CL; Ogletree, ML; Schumacher, WA, 1990
)
0.28
" Dose-response and dose-rate curves were constructed for ADP- and epinephrine-induced aggregation."( Low molecular weight heparin as an anticoagulant for in vitro platelet function studies.
Heyns, AD; van Wyk, V, 1990
)
0.28
" Topical application of exogenous PGF2 alpha and U46619 resulted in dose-dependent cerebral vasoconstriction, and the dose-response curve for each agonist was shifted to the right by the increasing concentrations of SQ29548 (10(-6)-10(-8) M)."( Effect of thromboxane A2/endoperoxide antagonist SQ29548 on the contractile response to acetylcholine in newborn piglet cerebral arteries.
Busija, DW; Wagerle, LC, 1990
)
0.68
" In separate groups of rats, the log dose-response curve for bolus intravenous injection of AII was shifted to the right by SQ-29,548 while that for PE was unaffected."( Thromboxane mediation of the pressor response to infused angiotensin II.
Welch, WJ; Wilcox, CS, 1990
)
0.28
" Consistent with this hypothesis were (i) a 60-70% decrease in SQ 26,655-stimulated platelet GTPase activity, (ii) a shift to the right of the dose-response curve for U46619-stimulated release of calcium [EC50, 275 +/- 51 nM (control)] vs."( Regulation of thromboxane receptor activation in human platelets.
FitzGerald, GA; Murray, R, 1989
)
0.28
" That is, the dose-response curves shifted to lower concentrations with increasing incubation times with UK-38485 prior to addition of aggregation agents."( Pharmacology of UK-38485 (dazmegrel), a specific inhibitor of thromboxane A2 synthetase.
Rebec, MV; Skrinska, VA, 1989
)
0.52
" In-vitro dose-response experiments revealed that CGS-12970 nonselectively inhibited renal allograft tissue TXB2 and 6-K-PGF1 alpha production in a dose-dependent manner."( Effects of the thromboxane synthesis inhibitor CGS-12970 on experimental acute renal allograft rejection.
Anderson, CB; Brunt, EM; Mangino, MJ; Von Doersten, P, 1989
)
0.28
"10 micrograms/ml) which was determined by dose-response curve of % increase in Pao by inhaled STA2 (0."( Bronchoconstrictive properties and potentiating effect on bronchial responsiveness of inhaled thromboxane A2 analogue (STA2) in guinea pigs.
Fujimura, M; Kurashima, K; Matsuda, T; Miyake, Y; Saito, M; Sakamoto, S, 1989
)
0.5
" Second, the dose-response curve for thromboxane A2, based on the amount of thromboxane B2 generated by lung strips contracted with leukotriene B4, was inconsistent with dose-response curves for lung strips contracted with a stable thromboxane A2 mimetic, U-46619 or with synthetic thromboxane A2 itself."( Myotropic activity of leukotriene B4 on lung parenchyma strips is not necessarily attributable to thromboxane A2 release.
Fitzpatrick, FA; Lawson, CF, 1988
)
0.77
" Etersalate inhibited at the lower dosage platelet function and decreased TXA2 levels, but PGI2 generation from rat aortic rings was stimulated when incubated with plasma from etersalate-treated donors."( Effect of etersalate on human platelet responsiveness. A study in healthy volunteers.
Armijo, M; Ortega, MP; Priego, JG; Sunkel, C, 1987
)
0.27
" In addition, analysis of dose-response curves to U46619 (0."( Thromboxane A2 and prostaglandin endoperoxide receptors in platelets and vascular smooth muscle.
Halushka, PV; Knapp, DR; Mais, DE; Saussy, DL, 1985
)
1.71
"5 mg/kg dosage had no significant effects."( The effects of colchicine on prostaglandin I2 and thromboxane A2 biosynthesis in the rat dental pulp.
Hirafuji, M; Ogura, Y, 1988
)
0.53
" A dose-response curve was achieved for all three cyclooxygenase products with the calcium ionophore A23187."( Human peritoneal eosinophils and formation of arachidonate cyclooxygenase products.
Foegh, ML; Maddox, YT; Ramwell, PW, 1986
)
0.27
" We conclude that long-term dosing with 27 mg ECA three times daily results in profound inhibition of platelet TXA2 production, and diminished in vitro and in vivo platelet reactivity."( Low-dose enteric-coated aspirin: a practical approach to continuous-release low-dose aspirin and presystemic acetylation of human platelet cyclooxygenase.
Deykin, D; Faigel, D; Jakubowski, JA; Stampfer, MJ; Vaillancourt, R, 1986
)
0.27
"In normocapnic and deeply hypocapnic guinea-pig heart-lung-preparations (HLPs), dose-response relationships were estimated for the bronchoconstrictor and pulmonary hypertensive responses to histamine (H), 5 hydroxytryptamine (5HT), arachidonic acid (AA) and U-46619, a prostaglandin endoperoxide analogue acting on thromboxane (TXA2) receptors."( Arachidonic acid and pulmonary function in heart-lung-preparation of guinea-pig: modulation by PCO2.
Argiolas, L; Bedetti, C; Carpi, A; Del Basso, P, 1987
)
0.27
" Rabbits were fed a diet supplemented with 2% cholesterol and 8% peanut oil for 12 weeks with or without UK-38485 at a dosage that maintained 80% to 90% inhibition of TXA2 formation in serum."( Suppression of foam cell lesions in hypercholesterolemic rabbits by inhibition of thromboxane A2 synthesis.
Galang, CF; Gerrity, RG; Konieczkowski, M; Rebec, MV; Skrinska, VA,
)
0.36
" The volunteers also received 50 mg modified release capsules daily for 6 days to determine the effect on collagen, ADP and arachidonate induced platelet aggregation and thromboxane production, and to compare the pharmacokinetics after repeated dosing with the parameters obtained after the single dose."( Pharmacokinetics of low-dose oral modified release, soluble and intravenous aspirin in man, and effects on platelet function.
Bochner, F; Lloyd, JV; Morris, PM; Siebert, DM; Williams, DB, 1988
)
0.27
"0 micrograms/ml of leukotriene C4, while the pretreatment did not affect the histamine dose-response curve."( Secondary release of thromboxane A2 in aerosol leukotriene C4-induced bronchoconstriction in guinea pigs.
Fujimura, M; Kanamori, K; Matsuda, T; Miyake, Y; Uotani, K, 1988
)
0.59
" The effect of PTA2 on U46619 and CTA2 was dose-dependent over the dosage range of PTA2 tested (1."( U46619 and carbocyclic thromboxane A2-induced increases in tracheal mucous gel layer thickness.
Foxwell, MH; Smith, WL; Yanni, JM, 1988
)
0.59
" At the end of each dosing interval we measured platelet aggregation and thromboxane formation in response to four aggregating agents and to whole blood coagulation."( A dose-ranging study of the antiplatelet effect of enteric coated aspirin in man.
Bochner, F; Duncan, EM; Herd, CM; Lloyd, JV; Rodgers, SE; Tunbridge, LJ, 1987
)
0.27
" One-step extraction of UTXB2 with an octadecylsilyl-silica column was sufficient as pretreatment for TXB2 radioimmunoassay because recovery of UTXB2 was good, the eluate was parallel with the dose-response curve, and the value coincided with that obtained by the conventional method."( Increased thromboxane B2 excretion in diabetes mellitus.
Inaba, M; Ishii, J; Katayama, S; Kawazu, S; Maruno, Y; Omoto, A, 1987
)
0.27
" Oral dosing with U46619 or AH23848 produced a dose-related inhibition of ethanol-induced gastric mucosal damage in the conscious rat, and these effects were partially blocked by indomethacin treatment."( The effects of the stable thromboxane A2-mimetic, U46619, on gastric mucosal damage and gastric non-parietal secretion in the rat.
Bunce, KT; Clayton, NM, 1987
)
0.57
"litre-1) caused a significant rightward and downward shift of the dose-response curve."( Thromboxane A2 analogue induced coronary artery vasoconstriction in the rabbit.
Hattori, R; Kawai, C; Sakaguchi, K; Susawa, T; Takatsu, Y; Yui, N; Yui, Y, 1987
)
1.72
" Blood samples were drawn 0, 2, 4, and 6 hours and 7 days after dosing for determination in serum (from untreated or in vitro indomethacin-treated portions of the blood) of TxA2 and PGI2 by radioimmunoassay of their stable metabolites (TxB2 and 6-keto-PGF1 alpha)."( Kinetics of ibuprofen effect on platelet and endothelial prostanoid release.
Beyers, BJ; Bowen, RJ; Longenecker, GL; Shah, AK; Swift, IA, 1985
)
0.27
" Alternatively, the lack of drug efficacy may have resulted from either incomplete suppression of thromboxane biosynthesis and/or substitution for the biological effects of thromboxane A2 by prostaglandin endoperoxides during long-term dosing studies."( The biochemical pharmacology of thromboxane synthase inhibition in man.
FitzGerald, GA; Pedersen, AK; Reilly, IA, 1985
)
0.46
" Acetylsalicylic acid inhibition, calculated as IC50 by a dose-response curve, is more than ten fold higher for leukocytes vs platelets."( Differential effects of aspirin and indomethacin on platelet and leukocyte thromboxane A2 formation.
Colli, S; Maderna, P; Morazzoni, G; Stragliotto, E; Tremoli, E, 1985
)
0.5
"We tested the antiplatelet effects of low-dose aspirin in patients with occlusive cerebrovascular disease, because conventional dosage aspirin inhibits vascular synthesis of prostacyclin at the same time that it inhibits platelets."( Effects of low dose aspirin on platelet function in patients with recent cerebral ischemia.
Kent, JL; Levy, DE; Rudolph, D; Scherer, PB; Weksler, BB,
)
0.13
" We conclude that dazoxiben at this dosage is unlikely to be of practical clinical benefit in Raynaud's phenomenon."( A thromboxane synthetase inhibitor in Raynaud's phenomenon.
Hawkey, CJ; Jones, EW, 1983
)
0.27
" This action carried over to ex vivo situation following intraduodenal dosing as demonstrated in rabbits."( Inhibition of platelet aggregation by a new agent, 2,2'-dithiobis-(N-2-hydroxypropyl benzamide) (KF4939).
Nakamizo, N; Shuto, K; Yamada, K, 1983
)
0.27
" Blood was drawn before the study started, 3-4 h after the initial dosage, 12 h after the 10th dosage on the 5th day, and 3-4 h after the 11th (final) dosage on the 6th day."( The effect of sulphinpyrazone on whole blood thromboxane and prostacyclin generation in man.
Badenhorst, PN; Deckmyn, H; Vermylen, J, 1982
)
0.26
" Variation in tension with time (2 h) and the dose-response to thromboxane A2 analogue (U46619) and phenylephrine (PE) were measured in controls and treated rings."( Effect of rapamycin on rat aortic ring vasomotion.
Blaise, GA; Chen, H; Corbin, F; Daloze, PM; Parent, M, 1994
)
0.53
" The peptides produced dose-related increases in perfusion pressure, and dose-response curves to all six peptides were parallel."( Analysis of responses to angiotensin peptides in the hindquarters vascular bed of the cat.
Garrison, EA; Kadowitz, PJ; Osei, SY; Santiago, JA, 1995
)
0.29
" Potassium chloride, norepinephrine, serotonin and thromboxane A2 mimetic were used to obtain dose-response curves, permitting assessment of force of contraction and sensitivity."( [Vaso-reactive properties of radial and internal mammary arteries: application to coronary bypass surgery].
Acar, C; Chardigny, C; Descombes, JJ; Fabiani, JN; Jebara, V; Verbeuren, T, 1994
)
0.54
" infused over 2 min; n = 4-8 per group) produced a bell-shaped dose-response curve for MPAP and haematocrit, and evoked maximal increases of 12."( Intrinsic activity of the non-prostanoid thromboxane A2 receptor antagonist, daltroban (BM 13,505), in human platelets in vitro and in the rat vasculature in vivo.
Bertolino, F; Bessac, AM; Colpaert, FC; Delhon, A; Grelac, F; Lévy-Toledano, S; Maclouf, J; Maffre, M; Patoiseau, JF; Valentin, JP, 1995
)
0.56
" However, we cannot exclude the possibility that intermittent bolus-like dosing of nicotine from cigarettes could have different effects from those produced by continually released transdermal nicotine."( Nicotine effects on eicosanoid formation and hemostatic function: comparison of transdermal nicotine and cigarette smoking.
Benowitz, NL; Fitzgerald, GA; Wilson, M; Zhang, Q, 1993
)
0.29
" The dose-response curve was shifted to the left, and the maximum effect was increased."( Effect of estradiol 17 beta on pressor responses of rat mesenteric bed to norepinephrine, K+, and U-46619.
Delaney, M; Farhat, MY; Ramwell, PW; Rego, A; Vargas, R; Wolfe, R, 1995
)
0.29
" In addition, pulmonary vascular reactivity was assessed by examining the dose-response relationship to the thromboxane analogue U-46619 pre- and post-CPB."( Prolonged pulmonary vascular hyperreactivity in conscious dogs after cardiopulmonary bypass.
Gillinov, AM; Murray, PA; Nishiwaki, K; Nyhan, DP; Redmond, JM, 1994
)
0.29
" Increases in perfusion pressure in response to bolus injections of U46619 were used to construct dose-response curves."( Reduced thromboxane receptor affinity and vasoconstrictor responses in placentae from diabetic pregnancies.
Hollander, AM; Mento, PF; Wilkes, BM, 1994
)
0.29
" Initial doses were randomly assigned and dosing intervals were separated by 2 weeks."( Effects of low-dose aspirin on in vitro platelet aggregation in the early minutes after ingestion in normal subjects.
Dabaghi, SF; Kamat, SG; Kleiman, NS; Marks, GF; Payne, J; Roberts, R; Schafer, AI, 1994
)
0.29
"The phenomenon of supercooperativity in platelet aggregation is manifested by the occurrence of clear-cut thresholds in dose-response relationships; in such cases the Hill coefficient has unusually high values."( Supercooperativity in platelet aggregation: substituted pyridyl isoxazoles, a new class of supercooperative platelet aggregation inhibitors.
Demina, OV; Shram, SI; Varfolomeev, SD; Vrzheshch, PV, 1994
)
0.29
" By pretreatment with 13-azaprostanoic acid (13-APA), a TXA2/endoperoxide receptor antagonist, the dose-response curve of BPS in the veins was shifted to the right."( The contractile mechanism of beraprost sodium, a stable prostacyclin analog, in the isolated canine femoral vein.
Ishikawa, M; Namiki, A, 1994
)
0.29
" Dose-response curves to CPA were shallower and maximal responses were weaker than those produced by the other agonists."( Interactions of adenosine A1 receptor-mediated renal vasoconstriction with endogenous nitric oxide and ANG II.
Barrett, RJ; Droppleman, DA, 1993
)
0.29
"Combined treatment with propranolol and reserpine enhanced acetylcholine-induced dose-response curves for bronchoconstriction in guinea pigs in vivo."( Pharmacological model for airway hypersensitivity produced by propranolol and reserpine in guinea pigs.
Goto, S; Inagaki, N; Koda, A; Nagai, H, 1993
)
0.29
" Dose-response curves (DRC) of U 46619-induced platelet aggregation were analysed by computerized non-linear curve fitting."( Fish oil preparations rich in docosahexaenoic acid modify platelet responsiveness to prostaglandin-endoperoxide/thromboxane A2 receptor agonists.
Clemens, MR; Jaschonek, K; Kirchner, M; Scheurlen, M, 1993
)
0.5
"We compared the effect of different aspirin schedules, dosages, and formulations on various bleeding time parameters including bleeding time, plasma and total blood volume, and levels of the stable metabolites of thromboxane A2 (TXA2) and prostacyclin (PGI2) (respectively, TXB2 and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha)) to determine the optimal dosage and formulation of aspirin to inhibit TXA2 production while sparing PGI2."( The effect of regular and enteric-coated aspirin on bleeding time, thromboxane, and prostacyclin.
Ebbeling, L; Gerrard, JM; Gow, JA, 1993
)
0.47
" Selective PAF, TXA2 and 5HT antagonists (WEB 2086, sulotroban and MCI-9042) clearly inhibited both the shape change and the aggregation induced by the appropriate agonist; in each case the effect of the antagonist was to move the dose-response curve to the right."( Studies on the effects of agonists and antagonists on platelet shape change and platelet aggregation in whole blood.
Heptinstall, S; Lösche, W; Sanderson, HM; Vickers, J, 1996
)
0.29
"9 h after dosing with food."( Effect of food intake on pharmacokinetics and effects of a new thromboxane A2 receptor antagonist, S-1452.
Ebihara, A; Fujimura, A; Kotegawa, T; Kumagai, Y; Ohashi, K; Shiga, T, 1996
)
0.53
"These results suggest that although the absorption of S-1452 is delayed and, consequently, its plasma concentration is decreased after dosing with food, the inhibitory effect on platelet aggregation is not significantly influenced after 50 mg of the drug."( Effect of food intake on pharmacokinetics and effects of a new thromboxane A2 receptor antagonist, S-1452.
Ebihara, A; Fujimura, A; Kotegawa, T; Kumagai, Y; Ohashi, K; Shiga, T, 1996
)
0.53
" We first characterized the dose-response relationship of bolus intrapulmonary injections of zaprinast (a cGMP-selective phosphodiesterase inhibitor) and nitric oxide solutions."( Effects of zaprinast and dissolved nitric oxide on the pulmonary circulation of fetal sheep.
Cassin, S; DeMarco, VG; Kadowitz, PJ; Skimming, JW, 1996
)
0.29
" Bradykinin elicited a biphasic dose-response curve in the formation of the vasoconstrictor and platelet aggregating thromboxane A2 (TxA2)."( The effect of bradykinin and substance P on the arachidonate cascade of platelets.
Gecse, A; Kis, B; Mezei, Z; Telegdy, G, 1996
)
0.5
"To examine abnormalities of prostanoid metabolism in lupus nephritis, which may affect renal function, and the effects of 4 day dosing of a selective thromboxane A2 (TXA2) synthetase inhibitor, DP-1904, on prostanoid metabolism."( Improvement of renal function with a selective thromboxane A2 synthetase inhibitor, DP-1904, in lupus nephritis.
Homma, M; Ichikawa, Y; Kameda, H; Tojo, T; Yoshida, T, 1996
)
0.75
" Dose-response curves to C5a (2, 10, and 50 nM) were obtained."( Contractile actions of C5a on isolated porcine coronary resistance and conductance arteries.
Amsterdam, EA; Gray, S; Rendig, SV, 1997
)
0.3
") administered 30 min before and 6 h after antigen challenge (double dosing regimen), did not affect the development of the early or late phase responses."( Effects of inhibitors of phosphodiesterase, on antigen-induced bronchial hyperreactivity in conscious sensitized guinea-pigs and airway leukocyte infiltration.
Broadley, KJ; Danahay, H, 1997
)
0.3
"5 kg) were infused with randomly selected doses of U46,619 and of 8-epi-PGF2 alpha to describe dose-response curves plotting pulmonary vascular resistance (PVRi) against dose."( Effects of 8-epi-prostaglandin F2 alpha and U46,619 on pulmonary hemodynamics in piglets.
Norberg, M; Thibeault, DW; Truog, WE, 1997
)
0.3
" These inhibitory effects were observed within 30 min and sustained for 24 h at a single dosage of 5 mg/kg of vapiprost."( The potent inhibition of vapiprost, a novel thromboxane A2 receptor antagonist, on the secondary aggregation and ATP release of human platelets.
Hiraishi, S; Horie, S; Ishii, H; Kazama, M; Kizaki, K; Kurusu, O; Nakahara, T; Noritake, S; Satoh, M; Yamada, M, 1997
)
0.56
"Discrete dose-response curves were obtained for the response to 5-HT (0."( Changes in reactivity towards 5-hydroxytryptamine in the renal vasculature of the diabetic spontaneously hypertensive rat.
Boston, PC; Hodgson, WC, 1997
)
0.3
" Threshold concentrations of ET-1 increased the maximum response to 5-HT, and markedly shifted the dose-response curve to the left."( Interactions between vasoconstrictors in isolated human cerebral arteries.
Barth, HL; Hempelmann, RG; Mehdorn, HM; Pradel, RH; Ziegler, A, 1997
)
0.3
" Notably, nearly identical dose-response curves were obtained when corresponding molar quantities of the most potent agents, SNP and SIN-1, were applied either via transbronchial or via intravascular routes, with respect to rapidity of onset, extent (pressure reduction to near baseline) and duration (>90 min) of vasorelaxation."( Efficiency of aerosolized nitric oxide donor drugs to achieve sustained pulmonary vasodilation.
Grimminger, F; Mayer, K; Otterbein, J; Schütte, H; Seeger, W; Spriestersbach, R; Walmrath, D, 1997
)
0.3
" Synergism might also lead to a reduction in dosage and a decreased risk of side-effects."( Rationale for the combination of anti-aggregating drugs.
Herman, AG, 1998
)
0.3
" The dose-response curve for methoxamine was shifted to the right and the maximum contractile response was impaired in mesenteric arterial beds from diabetic rats."( Possible modulation by endothelin-1, nitric oxide, prostaglandin I2 and thromboxane A2 of vasoconstriction induced by an alpha-agonist in mesenteric arterial bed from diabetic rats.
Kamata, K; Makino, A, 1998
)
0.53
" In contrast, repeated dosing (7 days) with ridogrel (3 to 25 mg/kg/day), had an antihypertensive effect in 12-week-old stroke-prone spontaneously hypertensive rats."( Effects of ridogrel, a thromboxane synthase inhibitor and receptor antagonist, on blood pressure in the spontaneously hypertensive rat.
Quest, DW; Wilson, TW, 1998
)
0.3
" The dose-response curve of TxA2 to SP exhibited a similar pattern to that detected for the cyclooxygenase pathway."( Effects of inflammatory neuropeptides on the arachidonate cascade of platelets.
Gecse, A; Kis, B; Mezei, Z; Telegdy, G,
)
0.13
" Each of the inhibitors attenuated ANG II-induced reductions in MBF, and all dose-response curves were shifted to the right to an approximately threefold higher ANG II dose."( ANG II- and TxA(2)-induced mesenteric vasoconstriction in rats is mediated by separate cell signaling pathways.
Bauer, J; Cavarape, A; Dau, C; Ehmke, H; Parekh, N; Schaefer, F, 1999
)
0.3
" Pretreatment with irbesartan inhibited U46619-induced vasoconstriction, and the dose-response curve was shifted to the right in a dose-dependent manner."( Novel angiotensin II AT(1) receptor antagonist irbesartan prevents thromboxane A(2)-induced vasoconstriction in canine coronary arteries and human platelet aggregation.
Brosnihan, KB; Diz, DI; Ferrario, CM; Fukuhara, M; Li, P, 2000
)
0.31
"The U46619-stimulated platelet aggregation was significantly inhibited by losartan in a dose-response manner."( [Effect of losartan on human platelet activation by thromboxane A2].
Casado, S; Castilla, C; Farré, J; Gómez, J; Guerra, JI; Jiménez, AM; López-Farré, A; Marcos, P; Montón, M; Núñez, A; Rico, L; Rodríguez-Feo, JA; Sánchez De Miguel, L, 2000
)
0.56
"Intravenous ASA in a dosage of 100 mg did not completely prevent TXA(2) production in AMI patients treated with streptokinase."( Incomplete thromboxane inhibition with 100 mg of intravenous acetylsalicylic acid in patients with acute ST elevation myocardial infarction: a placebo-controlled pilot trial.
Husted, SE; Jensen, HK; Kristensen, SD; Nielsen, HK; Vissinger, H; Ziegler, BK, 2001
)
0.31
" A portal perfusion pressure dose-response curve to methoxamine was performed in control and cirrhotic rat livers preincubated with vehicle, the nitric oxide synthase blocker N(G)-nitro-L-arginine (L-NNA), indomethacin cyclooxygenase (COX) inhibitor, L-NNA + indomethacin, or the thromboxane (TX) A(2) receptor blocker SQ 29,548."( Cyclooxygenase-derived products modulate the increased intrahepatic resistance of cirrhotic rat livers.
Abraldes, JG; Bosch, J; Bragulat, M; Corominola, H; García-Pagán, JC; Graupera, M; Peralta, C; Rodés, J, 2003
)
0.32
" Contraction dose-response curves were generated to determine maximal contraction force (F(max)) and pD2 (sensitivity) to phenylephrine in each experimental group."( Sepsis alters vessel contraction by adrenoceptor-induced nitric oxide and prostanoid.
Garrison, RN; Harris, PD; Kawabe, T; Zakaria, EL, 2003
)
0.32
" More recently, metronomic dosing regimens of standard chemotherapeutic agents without extended rest periods were shown to target the microvasculature in experimental animal models and result in significant antitumor activity [116-118]."( Therapeutic potential of selective cyclooxygenase-2 inhibitors in the management of tumor angiogenesis.
Gately, S; Kerbel, R, 2003
)
0.32
" Six anesthetized pigs (Ago group) received 6 consecutive injections of U-46619 at 30-min interval and were compared with six anesthetized pigs (Anta group) which received an increasing dosage regimen of BM-573 10 min before each U-46619 injection."( Effects of U-46619 on pulmonary hemodynamics before and after administration of BM-573, a novel thromboxane A2 inhibitor.
Benoit, P; D'Orio, V; Dogné, JM; Gérard, P; Ghuysen, A; Kolh, P; Lambermont, B; Limet, R; Masereel, B; Morimont, P; Tchana-Sato, V, 2003
)
0.54
" Dose-response experiments were also performed in vitro with single agents."( In vivo and in vitro effects of different anaesthetics on platelet function.
Ardito, G; Bruno, MF; Ciabattoni, G; Crocchiolo, R; de Cristofaro, R; Dordoni, PL; Frassanito, L; Landolfi, R; Proietti, R; Rocca, B, 2004
)
0.32
" BQ123 (1 microm) caused a rightward shift in the ET-1 dose-response curve, while indomethacin at a threshold concentration (28 nm) tended to have an opposite effect."( Endothelin-induced constriction of the ductus venosus in fetal sheep: developmental aspects and possible interaction with vasodilatory prostaglandin.
Adeagbo, AS; Coceani, F; Kelsey, L, 2004
)
0.32
" The local absorption ratio for the dosage after oral administration (Fa(dosage)) and the single-pass local absorption ratio for EHC (Fa') in the rats were similar and nearly 100%."( Pharmacokinetic analysis of ramatroban using a recirculatory model with enterohepatic circulation by measuring portal and systemic blood concentration difference in Sprague-Dawley and Eisai hyperbilirubinemic rats.
Moriwaki, T; Yamamoto, A; Yasui, H, 2004
)
0.32
"The objectives of the study were to (1) characterize the dose-response relationship to the TXA2 analog, U46619 (0."( Estrogen restores postischemic sensitivity to the thromboxane mimetic U46619 in rat pial artery.
Hurn, PD; Littleton-Kearney, MT; Qin, X, 2005
)
0.33
" Twelve anesthetized pigs were randomly assigned in two groups: in Ago group (n=6), the animals received six consecutive injections of U-46619 at 30 min interval, while in Anta group (n=6) they received an increasing dosage regimen of BM-573 10 min before each U-46619 injection."( Effects of BM-573, a thromboxane A2 modulator on systemic hemodynamics perturbations induced by U-46619 in the pig.
D'Orio, V; Dogné, JM; Ghuysen, A; Hanson, J; Kolh, P; Lambermont, B; Limet, R; Magis, D; Morimont, P; Tchana-Sato, V, 2005
)
0.65
" In addition, AYPGKF- and thrombin-induced TXA2 generation was significantly reduced in platelets from mice dosed with clopidogrel, confirming the results obtained with the human platelets."( P2Y12 receptor-mediated potentiation of thrombin-induced thromboxane A2 generation in platelets occurs through regulation of Erk1/2 activation.
Garcia, A; Kim, S; Kunapuli, SP; Prabhakar, J; Shankar, H, 2006
)
0.58
" Dose-response curve was bell shaped with a maximum effect at 10 nmol per site."( Thromboxane A2 induces itch-associated responses through TP receptors in the skin in mice.
Andoh, T; Kuraishi, Y; Narumiya, S; Nishikawa, Y; Nojima, H; Yamaguchi-Miyamoto, T, 2007
)
1.78
" Different dosage of Paeonol were used on diabetic animal models."( [Effect of cortex moutan on PGI2, TXA2, ET and NO in diabetic rats].
Liu, HQ; Min, CY; Qiu, WZ; Zhan, F, 2007
)
0.34
" Furthermore study indicated that blocking the thromboxane A2 receptor reduced dosage sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1 protein, a transcriptional repressor of StAR gene expression."( Involvement of the thromboxane A2 receptor in the regulation of steroidogenic acute regulatory gene expression in murine Leydig cells.
Grammas, P; Hutson, JC; Pandey, AK; Schiffer, RB; Stocco, DM; Wang, X; Yin, X, 2009
)
0.94
" Further research should consider increasing aspirin dosing frequency to twice daily, to allow sustained inhibition in such subjects."( Heterogeneity in platelet cyclooxygenase inhibition by aspirin in coronary artery disease.
Diodati, JG; Lordkipanidzé, M; Palisaitis, DA; Pharand, C; Schampaert, E, 2011
)
0.37
"Available evidence suggests that aspirin dosing must be individualized according to indication."( Aspirin dosing for the prevention and treatment of ischemic stroke: an indication-specific review of the literature.
Ansara, AJ; Arif, SA; Koehler, JM; Nisly, SA; Nordmeyer, ST, 2010
)
0.36
" In the present study, we investigated the determinants of aspirin-insensitive platelet TXA(2) biosynthesis and whether it could be further suppressed by changing the aspirin dose, formulation, or dosing interval."( Aspirin-insensitive thromboxane biosynthesis in essential thrombocythemia is explained by accelerated renewal of the drug target.
Dragani, A; Habib, A; Pagliaccia, F; Pascale, S; Patrono, C; Petrucci, G; Pocaterra, D; Ragazzoni, E; Rocca, B; Rolandi, G; Zaccardi, F, 2012
)
0.38
" A twice daily (bid) dosing is necessary to fully inhibit TXA2."( In vivo prostacyclin biosynthesis and effects of different aspirin regimens in patients with essential thrombocythaemia.
Barbieri, SS; Cavalca, V; Dragani, A; Pagliaccia, F; Patrono, C; Porro, B; Rocca, B; Squellerio, I; Tremoli, E; Veglia, F, 2014
)
0.4
" Rings of BMCA were mounted in isolated tissue chambers equipped with isometric tension transducers to obtain pharmacologic dose-response curves."( Multiple Actions of Phencyclidine and (+)MK-801 on Isolated Bovine Cerebral Arteries.
Chen, D; Kamel, IR; Wendling, KS; Wendling, WW, 2018
)
0.48
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (1)

RoleDescription
mouse metaboliteAny mammalian metabolite produced during a metabolic reaction in a mouse (Mus musculus).
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (2)

ClassDescription
epoxy monocarboxylic acidMonocarboxylic acids containing at least one epoxy group.
thromboxanes A
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Pathways (76)

PathwayProteinsCompounds
Hemostasis23944
Platelet activation, signaling and aggregation6315
Signal amplification86
Thromboxane signalling through TP receptor34
Metabolism14961108
Metabolism of lipids500463
Fatty acid metabolism113203
Arachidonic acid metabolism3682
Synthesis of Prostaglandins (PG) and Thromboxanes (TX)1135
Biological oxidations150276
Phase I - Functionalization of compounds69175
Cytochrome P450 - arranged by substrate type30110
Eicosanoids215
Signaling Pathways1269117
Signaling by GPCR24955
GPCR ligand binding19339
Class A/1 (Rhodopsin-like receptors)16136
Eicosanoid ligand-binding receptors117
Prostanoid ligand receptors75
GPCR downstream signalling17252
G alpha (q) signalling events7928
G alpha (12/13) signalling events84
Arachidonic Acid Metabolism2966
Leukotriene C4 Synthesis Deficiency2966
Piroxicam Action Pathway2967
Acetylsalicylic Acid Action Pathway2967
Etodolac Action Pathway2967
Ketoprofen Action Pathway2967
Ibuprofen Action Pathway5076
Rofecoxib Action Pathway2967
Diclofenac Action Pathway2967
Sulindac Action Pathway2967
Celecoxib Action Pathway3573
Ketorolac Action Pathway2967
Suprofen Action Pathway2967
Bromfenac Action Pathway2967
Indomethacin Action Pathway3067
Mefenamic Acid Action Pathway2967
Oxaprozin Action Pathway2967
Nabumetone Action Pathway2967
Naproxen Action Pathway2967
Diflunisal Action Pathway2967
Meloxicam Action Pathway2967
Valdecoxib Action Pathway2967
Antipyrine Action Pathway2967
Antrafenine Action Pathway2967
Carprofen Action Pathway2967
Etoricoxib Action Pathway2967
Fenoprofen Action Pathway2967
Flurbiprofen Action Pathway2967
Magnesium Salicylate Action Pathway2967
Lumiracoxib Action Pathway2967
Lornoxicam Action Pathway2967
Phenylbutazone Action Pathway2967
Nepafenac Action Pathway2967
Trisalicylate-Choline Action Pathway2967
Tolmetin Action Pathway2967
Tiaprofenic Acid Action Pathway2967
Tenoxicam Action Pathway2967
Salsalate Action Pathway2967
Salicylate-Sodium Action Pathway2967
Salicylic Acid Action Pathway2967
Acetaminophen Action Pathway2967
Prostaglandin and Leukotriene metabolism ( Prostaglandin and Leukotriene metabolism )2223
Blood clotting and drug effects05
Eicosanoid metabolism via cyclooxygenases (COX)137
Prostaglandin and leukotriene metabolism in senescence619
Quercetin and Nf-kB / AP-1 induced apoptosis09
Arachidonic acid (AA, ARA) oxylipin metabolism076
Folic acid network070
Quercetin and Nf-kB / AP-1 induced cell apoptosis09
Selenium micronutrient network095
Vitamin B12 metabolism050
Eicosanoid synthesis026
Folate metabolism156
Prostaglandin synthesis and regulation08
Arachidonic acid metabolism via COX (Cyclooxygenase) pathway035

Research

Studies (5,383)

TimeframeStudies, This Drug (%)All Drugs %
pre-19901955 (36.32)18.7374
1990's2081 (38.66)18.2507
2000's860 (15.98)29.6817
2010's426 (7.91)24.3611
2020's61 (1.13)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 65.37

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index65.37 (24.57)
Research Supply Index8.67 (2.92)
Research Growth Index4.31 (4.65)
Search Engine Demand Index116.55 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (65.37)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials224 (3.99%)5.53%
Reviews536 (9.54%)6.00%
Case Studies47 (0.84%)4.05%
Observational3 (0.05%)0.25%
Other4,807 (85.58%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]