Disease relevance of Isbogrel

• Any single specific inhibitor (CV-4151, a TXA2 synthetase inhibitor; AA-861, a 5-lipoxygenase inhibitor; or CV-3611, a radical scavenger) or a combination of two inhibitors showed no or only a slight antiproteinuric effect, but the combination of all three inhibitors significantly reduced PAN-induced proteinuria [1].
• In experiments in mice in vivo, CV-4151 (1 and 10 mg/kg i.v.) significantly inhibited the thrombocytopenia induced by U-44069 in a dose-dependent manner [2].
• Delay of the initiation of hypertension in spontaneously hypertensive rats by CV-4151, a specific thromboxane A2 synthetase inhibitor [3].
• CV-4151 significantly inhibited photochemically induced MCA thrombosis by oral (1 and 10 mg/kg) and intravenous (1 mg/kg) administration [4].
• Within 30 min after LAD occlusion, 15.6-33.3% of dogs experienced ventricular fibrillation (VF); CV-4151 had no significant effect on the incidence of VF [5].

High impact information on Isbogrel

• Comparison of GR32191, R68070 and CV-4151 upon U-46619- and collagen-induced platelet aggregation in vitro and ex vivo [6].
• CV-4151 inhibited TXA2 synthetase activity of medullary and cortical microsomes more effectively in 5w SHR than in age-matched WKY [3].
• Effects of thromboxane A2 synthase inhibitors (CV-4151 and ozagrel), aspirin, and ticlopidine on the thrombosis caused by endothelial cell injury [7].
• Beneficial effect of CV-4151 (Isbogrel), a thromboxane A2 synthase inhibitor, in a rat middle cerebral artery thrombosis model [4].
• CV-4151 might be a useful drug for the treatment of cerebral thrombosis and for the prevention of cerebral infarction [4].

Chemical compound and disease context of Isbogrel

• Two hours after p.o. administration, CV-4151 and ozagrel inhibited femoral vein platelet-rich thrombosis caused by endothelial injury with ID50 values of 2.46 and 13.7 mg/kg, respectively [7].

Biological context of Isbogrel

• CV-4151 was equipotent to OKY-1580 (IC50: 2.3 X 10 M), a well documented TXA2 synthetase inhibitor, in an in vitro TXA2 synthetase assay [8].

Anatomical context of Isbogrel

• To clarify the role of thromboxane (TX) A2 in arterial thrombus formation, we examined the antithrombotic effects of both a TXA2 synthetase inhibitor (CV-4151) and a TXA2 receptor antagonist (AA-2414) on the rabbit common carotid artery thrombosis which was induced by injury of the endothelium by treatment with 0.25% pronase solution [9].
• Skeletal muscle blood flow was measured by a hydrogen gas clearance method; the blood flow restored fully in the CV-4151 group, while it remained significantly low in the control group after 1 h of reperfusion (p < 0.05) [10].

Associations of Isbogrel with other chemical compounds

• The protective effect of a novel thromboxane (TX) synthetase inhibitor, (E)-7-phenyl-7-(3-pyridyl)-6-heptenoic acid (CV-4151), on myocardial damage due to an ischemic episode and reperfusion was investigated in anesthetized, open-chested dogs [5].
• Thus, CV-4151 did not significantly reduce the incidence of restenosis, perhaps due to endothelial denudation after angioplasty preventing an increase of the subendothelial local prostacyclin level [11].

Analytical, diagnostic and therapeutic context of Isbogrel

• Increase in TXB2 release into the great coronary vein during reperfusion was completely inhibited by CV-4151, whereas release of 6-keto-PGF1 alpha tended to increase during occlusion and reperfusion [5].
• In rats, serial oral administration of CV-4151 (10 mg/kg) once daily for 14 days produced a constant and marked reduction of serum TXB2 concentration with concomitant increase of serum immunoreactive 6-keto-PGF1 alpha concentration [8].
• In contrast, premedication with CV-4151 significantly improved the recovery of ATP (p < 0.01) [10].
• The sham group (n = 8) underwent the operation without ischemia-reperfusion; the control group (n = 8) with ischemia-reperfusion, and the CV-4151 group (n = 8) was pretreated with CV-4151 20 mg/kg [10].
• PCR showed the same tendency as ATP; CV-4151 also improved the recovery of PCR significantly (p < 0.05), but CV-4151 did not prevent the production of lipid peroxides [10].

References