Disease relevance of Amafolone

• Effect of the aminosteroid U74006F after cardiopulmonary arrest in dogs [1].
• The number of positively stained axons was significantly reduced in the aminosteroid and combination therapy groups at all three postinjury times (p = 0.01) and in the hypothermia groups treated at 10 or 25 min (p = 0.01) but not at 40 min after injury [2].
• Control animals were operated but not subjected to ischemia-reperfusion; the untreated group underwent to ischemia-reperfusion without pharmacological treatment; while the treated group received the aminosteroid (4 mg/kg) before coronary occlusion and at the time of reperfusion [3].
• The effects of postligation administration of ORG 6001 and disopyramide on early ischaemia-induced arrhythmias in the anaesthetized rat [4].
• 1 The effect of the antidysrhythmic aminosteroid, ORG 6001, on hypothermia-induced ventricular fibrillation was investigated in cats anaesthetized with pentobarbitone [5].

High impact information on Amafolone

• The aminosteroid phospholipase C antagonist U-73122 (1-[6-[[17-beta-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione) potently inhibits human 5-lipoxygenase in vivo and in vitro [6].
• These results suggest that U73122 does not act as a general serine-threonine protein kinase inhibitor, and the aminosteroid inhibition of the cGMP-induced Ca2+ release may interfere with ADP ribosyl cyclase activity [7].
• We investigated the effects of U-73122, an aminosteroid inhibitor of PL-C dependent processes, on TRH-stimulated second messenger pathways and on PRL secretion in GH3 rat pituitary cells [8].
• U-73122, an aminosteroid phospholipase C antagonist, noncompetitively inhibits thyrotropin-releasing hormone effects in GH3 rat pituitary cells [8].
• Effect of the aminosteroid U73122 on prostaglandin E(2) production in a murine clonal osteoblast-like cell line, MC3T3-E1 [9].

Chemical compound and disease context of Amafolone

• We studied the effects of the aminosteroid U-74389G (21-[4-(2, 6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]-pregna-1,4,9(11)- triene-3,20-dione(2)-2-butenenedionate), a putative inhibitor of lipid peroxidation, which protects the rat myocardium after ischemia and reperfusion [10].
• We have demonstrated that the aminosteroid, U-73122 (1-(6-([17 beta-3-methoxyestra-1,3,5(10)-trien-17-yl]amino)hexyl)-1H-pyrrole- 2,5-dione) blocks agonist induced down-regulation of neurotensin receptors in murine neuroblastoma clone N1E-115 cells [11].
• LND-623 is a new aminosteroid analog of ouabain, with a greater separation between efficacy and toxicity than ouabain [12].
• MAIN RESULTS: Two randomised controlled trials have examined the effect of the aminosteroid tirilazad mesylate on death and disability following head injury [13].

Biological context of Amafolone

• Voltage- and time-dependent depression of maximum rate of depolarization of guinea-pig ventricular action potentials by two steroidal antiarrhythmic drugs, CCI 22277 and ORG 6001 [14].
• Brief incubation of cells with the aminosteroid resulted in greater than 90% inhibition of lipid peroxidation during subsequent 2-h incubations with tert-buOOH and addition of U74500A during treatment of cells with tert-buOOH halted further lipid peroxidation [15].
• The aminosteroid U73122 (1-[6-1[17beta-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1 H-pyrrole-2,5-dione) has been widely used as an inhibitor of phospholipase C, the enzyme mediating phosphoinositide hydrolysis [16].
• Ion transport ATPases as targets for free radical damage. Protection by an aminosteroid of the Ca2+ pump ATPase and Na+/K+ pump ATPase of human red blood cell membranes [17].
• Block of neurotensin receptor down-regulation by an aminosteroid in N1E-115 cells [11].

Anatomical context of Amafolone

• All these results lead to the conclusion that aminosteroid treatment, at least in the conditions of the present study, is effective in reducing the morphological and biochemical alterations occurring in ischemic-reperfused myocardium [3].
• Coronary artery ligation in anaesthetized rats as a model for the assessment of antidysrhythmic activity; the effects of lignocaine, propranolol and ORG 6001 [proceedings] [18].
• Effect of the aminosteroid, U73122, on Ca2+ uptake and release properties of rat liver microsomes [19].
• The aminosteroid U73122 has been established as potent, selective, and cell-permeable inhibitor C-type phosphatidylinositol-specific phospholipases (PI-PLCs), and has been used to define a contribution of PI-PLCs as part of exocytotic signalling pathways in rat peritoneal mast cells (RPMCs) [20].
• U-73122, an aminosteroid phospholipase C inhibitor, may also block Ca2+ influx through phospholipase C-independent mechanism in neutrophil activation [21].

Associations of Amafolone with other chemical compounds

• The hypothermia-induced elevation of blood lactate was less in cats treated with the aminosteroid [5].
• 1 CCI22277 (methyl 2 beta-ethoxy-2 alpha-hydroxy-11 alpha-(3-methylbutylamino)-5 alpha-androstane-17 beta-carboxylate hydrochloride) is an aminosteroid with antiarrhythmic properties in animal models [22].
• Myocardial concentration of malondialdehyde, which was undetectable in the control group, was raised in all the animals after reperfusion, but this effect was significantly less marked with aminosteroid treatment [3].

Gene context of Amafolone

• [Ca2+]i signals stimulated by both CCK-8 and JMV-180 were blocked by the aminosteroid U-73122 [23].
• All these alterations, notably neutrophil infiltration, were attenuated by aminosteroid treatment [3].
• The anaesthetic action and modulation of GABAA receptor activity by the novel water-soluble aminosteroid Org 20599 [24].
• The response to neurotensin was found to be inhibited by the aminosteroid U-73122, a putative inhibitor of phospholipase C-dependent processes, indicating that this drug may act at the G-protein level [25].
• The aminosteroid reduced by 50% motoneuron NADPH-diaphorase activity [26].

Analytical, diagnostic and therapeutic context of Amafolone

• Four water-soluble aminosteroid intravenous anaesthetic agents (ORG 20380, 20549, 21047 and 20599) were investigated for antinociceptive properties following intrathecal injection in rats [27].
• Similarly, 6 of 15 animals that had radiosurgery alone showed evidence of vasculopathy (p = 0.005) compared to no animals in the control group and only 2 of 27 aminosteroid-treated animals [28].
• 2 ORG 6001 (total dose, 10 mg/kg, by intravenous injection) reduced both the incidence of fibrillation and the temperature at which it occurred [5].
• Influence of aminosteroid and glucocorticoid treatment on inflammation and immune function during cardiopulmonary bypass [29].

References