Disease relevance of CGS 8515

• 5. We conclude that leukotrienes have a major role in guinea-pig cardiac anaphylaxis, and that CGS 8515 has a cardio-protective action [1].
• BW755c, CGS-8515, and FPL-55712 all prevented an otherwise significant fall in VF threshold during coronary occlusion (p less than 0.01) independent of an effect on effective refractory period, heart rate, or blood pressure [2].
• The cyclooxygenase inhibitor aspirin (50 mg kg-1) and the dual cyclooxygenase/lipoxygenase inhibitor BW 755C (0.25-10.0 mg kg-1) were found to produce a significant protection against the arrhythmias, whereas aspirin (100 mg kg-1) and CGS 8515 were found to be ineffective [3].

High impact information on CGS 8515

• 3. CGS 8515 (0.03-1.0 microM), an inhibitor of 5-lipoxygenase, dose-dependently inhibited ovalbumen-induced coronary vasoconstriction and leukotriene-C4 release [1].
• The oral bioavailability of V was improved to 27%, compared to 2% for the parent compound, CGS 8515 [4].
• Indomethacin (cyclooxygenase inhibitor) potentiated and CGS 8515 (5-lipoxygenase inhibitor) attenuated PAF-induced increases in total peripheral resistance (TPR) from 2.5 to 4 h [5].
• 4. CGS 8515 (a specific 5-lipoxygenase inhibitor, 10(-6) M) did not change BK (10(-5) M)-induced relaxation on the muscle alone, and caused an increase of BK-induced relaxation on the muscle within epithelium-intact trachea compared with that obtained without CGS 8515 [6].
• Digoxin-induced acute rise in mean arterial blood pressure was not affected by any of drug treatment except WEB 2086 (10.0 mg.kg-1) in combination with CGS 8515 [7].

Biological context of CGS 8515

• 1. CGS 8515 selectively inhibited 5-LO (IC50 = 0.1 microM) with negligible effect on CO, 12-LO, 15-LO and TxS at concentrations up to 100 microM [8].

Anatomical context of CGS 8515

• 4. CGS 8515, at oral doses as low as 5 mg/kg, significantly suppressed exudate volume and leukocyte migration in the carrageenan-induced pleurisy and sponge models in the rat [8].

Gene context of CGS 8515

• Characterization of CGS 8515 as a selective 5-lipoxygenase inhibitor using in vitro and in vivo models [9].
• CGS 8515 blocked the TNF-alpha + IL-1 alpha-induced increases (P < 0.05) in mean aortic pressure, total peripheral resistance (4-6 h), VD/VT (5-6 h), and, at 6 h, attenuated the increases in Ppa, PVR, and AaDO2 [10].

Analytical, diagnostic and therapeutic context of CGS 8515

• Determination of the 5-lipoxygenase inhibitor (CGS 8515) in plasma by high-performance liquid chromatography using reductive electrochemical detection [11].

References