Disease relevance of S 1452

• CONCLUSIONS: Our results suggest that thromboxane A2 is closely related to postischemic brain injury in the early phase of recirculation and that S-1452 may have a protective effect on postischemic brain injury [1].
• Pretreatment with S-1452 (10 mg/kg PO) also significantly decreased the areas of infarction in the front parts of the cerebrum [1].
• METHODS: We evaluated the effects of S-1452, a novel thromboxane A2 receptor antagonist, on brain edema, infarct areas, and survival rate in rats with middle cerebral artery occlusion [1].
• These results indicate that aerosolized S-1452 may be useful in treating bronchial asthma [2].
• Oral administration of S-1452, a selective TxA2 receptor antagonist, markedly suppressed bronchial hyperresponsiveness without affecting cellular responses, pulmonary edema and production of PGs and cytokines [3].

High impact information on S 1452

• A TXA(2) synthase inhibitor, OKY-046, and a TXA(2) receptor antagonist, S-1452, reduced LPS-induced hepatic microcirculatory dysfunction by inhibiting TNF alpha production [4].
• Effect of a novel thromboxane A2 receptor antagonist, S-1452, on postischemic brain injury in rats [1].
• Isobologram analysis showed that the combination of CDDP with S-1452 or AA-2414 produced supra-additive or additive effects in each cell line [5].
• This histamine-independent bronchoconstriction was markedly suppressed by S-1452 at a low dose of 0.1 mg kg-1 [6].
• Ice and Ced-3 homolog (ICH-1L) expression was significantly lower in PC-9/CDDP and was up-regulated by S-1452 or ONO-NT-126 [7].

Chemical compound and disease context of S 1452

• These results indicate that TxA(2) as well as histamine may play an important role in antigen-induced nasal plasma exudation in guinea pigs, and S-1452 can be expected to be useful for the treatment of allergic rhinitis [8].
• Furthermore, we examined the effect of S-1452, a TXA2 receptor antagonist, on the antigen-induced airway obstruction and AHR in guinea pigs [9].
• During the 3-hr observation period following endotoxin administration, ibuprofen and S-1452 showed only early protection and TCV-309 showed late attenuation of the endotoxin-induced hypotension [10].

Biological context of S 1452

• IC50 values to CDDP using MTT assay were decreased 2.1- and 4.6-fold respectively by treatment with 250 or 500 microM S-1452, for a 2 h simultaneous drug exposure, and those of PC-9/CDDP, a CDDP-resistant cell line, were decreased 3.1- and 6.1-fold [5].
• These results suggest that although S-1452 is rapidly eliminated in plasma, its inhibitory effects on platelet aggregation persist for a longer period [11].
• In addition, 0.1 mg x kg(-1) S-1452, a thromboxane A2 antagonist, or saline was given intravenously 5 min before UNDW inhalation in sensitized animals [12].
• To study the pharmacokinetics of a new thromboxane A2 (TXA2) receptor antagonist, S-1452, eight healthy volunteers were given placebo or S-1452 orally on four occasions in step-wise increasing doses of 10 mg, 25 mg, and 50 mg separated by 2-week intervals [11].
• Bleeding time was slightly prolonged after a single dose of S-1452 [11].

Anatomical context of S 1452

• Exposure of the nasal cavity of guinea pigs to aerosolized U-46619, a TxA2 mimetic, also resulted in a marked increase in intranasal pressure, and this could be almost completely suppressed by S-1452 [13].
• The in vitro uptake of lipo [14C] S-145-Me by fresh human neutrophils and an eosinophil cell line was respectively 7 times and 3.5 times higher than that of [14C] S-1452 [14].
• The accumulation of inflammatory cells by antigen provocation in bronchial alveolar lavage fluid (BALF) was inhibited by ketotifen but not by S-1452 [15].
• S-1452, a potent and selective TXA2 receptor antagonist, blocks the receptors of vascular smooth muscle cells (VSMC) as well as platelets [16].
• For the short-term study, eighteen rabbits after balloon injury of iliac artery were assigned to 3 groups; systemic administration of S-1452, single local administration of S-1452 using a local delivery balloon, and single local administration of saline solution [16].

Associations of S 1452 with other chemical compounds

• Oral administration of S-1452 or intravenous administration of diphenhydramine significantly but incompletely reduced the increase in intranasal pressure following exposure of the nasal cavity of guinea pigs to aerosolized OA [13].
• However, pretreatment with Y-24180 or S-1452 significantly attenuated the increase in extracellular AR after reperfusion, while it exerted no effect on the changes in extracellular ascorbate or tissue pO2 throughout the experimental period [17].
• Cysteine protease p32(CPP32) protein expression was lower in PC-9/CDDP but was not changed by S-1452, cisplatin, or cotreatment with cisplatin and S-1452 [7].
• The effect of a novel thromboxane A2 (TXA2) receptor antagonist (S-1452) on the antigen-induced bronchoconstriction and airway hyperresponsiveness in guinea pigs [15].
• Furthermore, bacterial lipopolysaccharide-induced AHR in guinea pigs was clearly suppressed by RS-601 but not by pranlukast and S-1452 [18].

Gene context of S 1452

• Moreover, the effects of the thromboxane (TX) A(2) (TXA(2)) synthase inhibitor OKY-046 and the TXA(2) receptor antagonist S-1452 on hepatic responses to I/R exhibited results similar to those obtained with COX inhibitors [19].
• The degree and positive rate of ET-1 and ET-3 staining were significantly higher in the NTN group than in the S-1452 group [20].
• Pharmacokinetics of a new thromboxane A2 receptor antagonist, S-1452, and its effect on platelet aggregation in healthy volunteers [11].
• There was no significant difference in the airway tissue distribution of labelled lipo S-145-Me versus S-1452 after 2 or 5 min of inhalation, but the encapsulated drug showed marked accumulation in the lungs after 30 min of inhalation [14].
• To address this question, we explored the influences of OKY-046 (a TxA2 synthase inhibitor) and S-1452 (a TP receptor antagonist) on eosinophilic inflammation of the airways using a murine model [21].

Analytical, diagnostic and therapeutic context of S 1452

• Proteinuria was observed in 3, 7 and 8 mice in the control group, and 0, 2 and 5 mice in the S-1452 group at 12, 16 and 20 weeks after initiation of S-1452 treatment, respectively [22].
• S-1452 50 mg or placebo were given orally to 8 healthy subjects at 10.00 h (day trial) or 22.00 h (night trial) according to a cross-over design [23].
• 3. No significant difference was observed in tail-cuff blood pressure (BP) between vehicle- and S-1452-treated SHR before and at 5 and 11 weeks after treatment [24].

References