Disease relevance of PIRMAGREL

• Thus, t-PA and CGS-13080 exert synergistic effects in preserving myocardial integrity in cats subjected to acute myocardial ischemia followed by reperfusion [1].
• However, we reported previously that thromboxane metabolite excretion is increased in CsA-treated renal allograft recipients with evidence of CsA toxicity and that 48-hr intravenous infusion of the selective thromboxane synthase inhibitor CGS 13080 improves renal function in such patients [2].
• Administration of 2 mg/kg of CGS 13080 reduced significantly the mass of the right ventricular thrombus, but did not prevent completely the reduction in the circulating platelet count or death [3].
• Treatment with CGS-16617 (1 microgram/kg) or CGS-13080 (200 micrograms/kg) alone did not alter significantly postoligemic hypotension or the increase in plasma cathepsin D activity in shocked rats, compared with hemorrhaged rats receiving only their vehicle [4].
• We speculate that CGS 13080 may be efficacious in the treatment of human pregnancy-induced hypertension [5].

High impact information on PIRMAGREL

• Effects of CGS-13080, a thromboxane inhibitor, on pulmonary vascular resistance in patients after mitral valve replacement surgery [6].
• We studied the effects of a thrombolytic agent (t-PA) and a thromboxane synthetase inhibitor (CGS-13080) in a model of myocardial ischemia and reperfusion [1].
• Administration of the same doses of both t-PA and CGS-13080 together markedly attenuated creatine kinase release to 10 +/- 2 IU/mg protein (p less than 0.01) and reduced the area of necrotic tissue to 9 +/- 2% of the area at risk and only 1.3 +/- 0.3% of the left ventricle (p less than 0.001) [1].
• We compared the biochemical selectivity and platelet inhibitory actions of single doses of aspirin, a cyclooxygenase inhibitor, with imidazo(1,5-2)pyridine-5-hexanoic acid (CGS 13080), an inhibitor of thromboxane synthase [7].
• High doses of CGS 12970 and CGS 13080 caused an apparent enhancement of platelet accumulation which was associated with pooling of blood in the thorax, as measured by either 131I-labelled human albumin or 51Cr-labelled erythrocytes [8].

Biological context of PIRMAGREL

• Pretreatment with a TxA2 synthase inhibitor, CGS 13080 (10 mg/kg, i.v., -10 min), had no effect on PGD2- or 9 alpha, 11 beta-PGF2-induced bronchoconstriction, suggesting that these prostanoids did not provoke the release of TxA2 [9].
• No change occurred in blood pressure or glomerular filtration rate (GFR): 95.2 +/- 7.2, control versus 95.0 +/- 9.0, CGS 13080 (ml/min); or renal plasma flow (RPF): 363.2 +/- 34.2, control, versus 373.2 +/- 31.2, CGS 13080, (ml/min) [10].
• Collagen-induced platelet aggregation was inhibited at 2 hours after CGS-13080 administration [11].
• CGS 13080, imidazo[1,5-a]pyridine-5-hexanoic acid, was evaluated for perinatal and postnatal effects in third trimester pregnant guinea pigs and their offspring [12].
• Sodium nitroprusside, a vasodilator, inhibited the rise in portal pressure caused by PMA to the same extent as CGS 13080 or BM 13.177 but reduced the increase in glycogenolysis only by 25% [13].

Anatomical context of PIRMAGREL

• Each group included dogs that received either the TXA2 synthase inhibitor CGS 13080 or its vehicle (controls) starting 30 min before renal artery clamping and lasting to the end of the experiment [14].
• CGS-13080 infusion decreased mean pulmonary artery pressure, SVR, and airway pressure after protamine injection relative to controls [15].
• This observation may be correlated to the reported redistribution of fluid volume to the thorax of guinea pigs given intravenous injections of CGS 13080 [12].
• Protection of ischemic cat myocardium by CGS-13080, a selective potent thromboxane A2 synthesis inhibitor [16].
• To define more clearly the mechanism of action of CGS-13080, we also studied it effects on isolated cat coronary arteries, in vitro aggregation of cat platelets, and production of thromboxane B2 (TxB2) from cat platelet-rich plasma (PRP) [16].

Associations of PIRMAGREL with other chemical compounds

• Pretreatment with the cyclo-oxygenase inhibitor, ibuprofen (6.25 mg kg-1), or with the thromboxane synthetase inhibitors dazoxiben (2.5 mg kg-1), CGS-13080, or OKY-046 1 mg kg-1) increased survival rates to 83-100% [17].

Gene context of PIRMAGREL

• Pretreatment with CGS 13080 resulted in a shorter time to tPA-induced reperfusion, greater incidence of reperfusion and increased the magnitude of femoral artery blood flow achieved after effective thrombolysis [18].
• Furthermore, pretreatment with CGS 13080 resulted in a greater than 10-fold enhancement in the effective dose of tPA [18].

Analytical, diagnostic and therapeutic context of PIRMAGREL

• Greater attenuation of TxB2 was found after treatment with the drug combination (P less than .01 from vehicle, P less than .05 from CGS-13080 alone) [4].
• No adverse hemodynamic or other effects attributable to CGS-13080 occurred during or immediately following cardiopulmonary bypass [19].
• The control group was fed a standard pellet diet, while the treated groups were fed the standard diet supplemented with either a low dose (0.8 g per 10 kg pellet) or a high dose (1.6 g per 10 kg pellet) of CGS 13080 [20].
• The effect of a thromboxane A2 synthetase inhibitor (CGS-13080) on canine intestine was studied using a single dose of radiation, and radioactive microspheres were used to determine resultant blood flow [21].

References