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Chemical Compound Review:

Y 20811 sodium4-[hydroxy-(5-imidazol- 1-yl-2...

Synonyms:

Matsumoto, Y. et al., Mikashima, H. et al., Sato, N. et al., Sakai, H. et al., Fujimura, M. et al., et al.

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Disease relevance of 4-[hydroxy-(5-imidazol-1-yl-2-methyl-phenyl)methyl]-3,5-dimethyl-benzoic acid

The weight of the thrombus in the Y-20811-treated group was significantly less than that in the control group (P less than 0.01) [1].
These results suggest that Y-20811 prevents coronary thrombosis by the inhibition of TXA2 production around the electrically injured lumen of the coronary artery [1].
To examine effects of a new thromboxane synthetase inhibitor, Y-20811, on infarct size, neutrophil accumulation, and arrhythmias, coronary artery was occluded for 90 min and reperfused for 6 h in anesthetized dogs [2].
Y-20811 significantly suppressed the infarction number and the incidence at doses of 1 mg/kg and 10 mg/kg (p.o.), respectively [3].
These results indicate that Y-20811 may be useful in preventing embolic cerebral infarction and transient ischemic attacks [3].

High impact information on 4-[hydroxy-(5-imidazol-1-yl-2-methyl-phenyl)methyl]-3,5-dimethyl-benzoic acid

Dibutyryl cGMP (500 microM) also induced Cl- secretion, which was sensitive to ONO-3708 (10 microM) and Y-20811 (1 microM), and increased the release of TXA2 from the mucosa [4].
The SNP-induced Cl- secretion was inhibited in a concentration-dependent manner by the TXA2 receptor antagonist ONO-3708 (IC50 = 2 microM) and the TX synthase inhibitor Y-20811 (IC50 = 0.4 microM) [4].
In addition, inhibition of TXA2 production by Y-20811 still remained after washing the drug-pretreated microsomes, whereas that of dazoxiben completely disappeared [5].
Effects of Y-20811, a thromboxane A2 synthetase inhibitor, on experimentally induced coronary thrombosis in anesthetized dogs [1].
Effects of a thromboxane synthetase inhibitor, Y-20811, on infarct size, neutrophil accumulation, and arrhythmias after coronary artery occlusion and reperfusion in dogs [2].

Chemical compound and disease context of 4-[hydroxy-(5-imidazol-1-yl-2-methyl-phenyl)methyl]-3,5-dimethyl-benzoic acid

The effects of Y-20811, a selective inhibitor of thromboxane A2 (TXA2) synthetase, on blood flow and local levels of immunoreactive thromboxane B2 (i-TXB2) and 6-keto prostaglandin F1 alpha (i-6-keto PGF1 alpha) in the coronary artery were investigated in the canine model of coronary thrombosis [1].

Biological context of 4-[hydroxy-(5-imidazol-1-yl-2-methyl-phenyl)methyl]-3,5-dimethyl-benzoic acid

Administered orally to rabbits, Y-20811 at a dose of 1 mg/kg decreased serum TXB2 concomitant with increasing 6-keto PGF1 alpha and at a dose of 3 mg/kg inhibited AA-induced platelet aggregation, in both cases for at least 48 hours [6].
The drugs were orally administered to rabbits at 24 and 1 hour before injection of endotoxin (5 mg/kg, i.v.). Y-20811 (1 mg/kg) promoted the recovery of decreased platelet counts, and inhibited hypotension induced by endotoxin [7].

Anatomical context of 4-[hydroxy-(5-imidazol-1-yl-2-methyl-phenyl)methyl]-3,5-dimethyl-benzoic acid

Y-20811 had a tendency to decrease the number of total cells, macrophages and eosinophils in a dose-dependent manner [8].

Associations of 4-[hydroxy-(5-imidazol-1-yl-2-methyl-phenyl)methyl]-3,5-dimethyl-benzoic acid with other chemical compounds

Phase I study of Y-20811, a new long-acting thromboxane synthetase inhibitor by oral administration [9].

Analytical, diagnostic and therapeutic context of 4-[hydroxy-(5-imidazol-1-yl-2-methyl-phenyl)methyl]-3,5-dimethyl-benzoic acid

Serum TXA2 (estimated as TXB2) production was inhibited significantly from 1 to 72 hr after the oral administration of unlabeled Y-20811 (3 mg/kg), which temporally resembled the change of the platelet Y-20811 concentration [5].
The level of i-6-keto PGF1 alpha tended to increase slightly in the Y-20811-treated, but not in the control group [1].

References

Effects of Y-20811, a thromboxane A2 synthetase inhibitor, on experimentally induced coronary thrombosis in anesthetized dogs. Matsumoto, Y., Ochi, H., Aihara, K., Inui, J., Ikegami, K. Eur. J. Pharmacol. (1992) [Pubmed]
Effects of a thromboxane synthetase inhibitor, Y-20811, on infarct size, neutrophil accumulation, and arrhythmias after coronary artery occlusion and reperfusion in dogs. Sato, N., Endo, T., Kiuchi, K., Hayakawa, H. J. Cardiovasc. Pharmacol. (1993) [Pubmed]
Effect of Y-20811, a thromboxane synthetase inhibitor, on photochemically induced cerebral embolism in rabbits. Fujimura, M., Mikashima, H. Thromb. Res. (1993) [Pubmed]
Nitric oxide-induced Cl- secretion in isolated rat colon is mediated by the release of thromboxane A2. Sakai, H., Suzuki, T., Murota, M., Takahashi, Y., Takeguchi, N. J. Physiol. (Lond.) (2002) [Pubmed]
Irreversible inhibition of thromboxane (TX) A2 synthesis by Y-20811, a selective TX synthetase inhibitor. Mikashima, H., Ochi, H., Muramoto, Y., Hirotsu, K., Arima, N. Biochem. Pharmacol. (1992) [Pubmed]
Effects of Y-20811, a long-lasting thromboxane synthetase inhibitor, on thromboxane production and platelet function. Mikashima, H., Ochi, H., Muramoto, Y., Yasuda, H., Tsuruta, M., Maruyama, Y. Thromb. Res. (1986) [Pubmed]
Protective effect of Y-20811, a long-lasting thromboxane synthetase inhibitor, on endotoxin shock in rabbits. Mikashima, H., Muramoto, Y. Thromb. Res. (1990) [Pubmed]
Effect of Y-20811, a long-lasting thromboxane A2 synthetase inhibitor, on antigen-induced airway hyperresponsiveness in guinea pigs. Kagoshima, M., Tomomatsu, N., Aratani, H., Terasawa, M. Int. Arch. Allergy Appl. Immunol. (1991) [Pubmed]
Phase I study of Y-20811, a new long-acting thromboxane synthetase inhibitor by oral administration. Nakashima, M., Uematsu, T., Takiguchi, Y., Mizuno, A., Kanamaru, M. Journal of clinical pharmacology. (1989) [Pubmed]

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