Disease relevance of UK 37248

• 5 We conclude that UK 37248 provides significant beneficial effects in experimental endotoxic shock in the rat [1].
• 4 UK 37248 significantly improved the endotoxin-induced thrombocytopaenia, disseminated intravascular coagulation, hypoglycaemia and lysosomal labilization [1].
• 3 UK 37248 significantly (P less than 0.05) reduced the endotoxin mortality rate at 24 h from 69% (n = 13) to 30% (n = 13), UK 37248 also reduced splanchnic infarction from 90% (n = 20) to 6% (n = 16) [1].
• 1 The thromboxane A2 synthetase inhibitor dazoxiben (UK 37248) was given orally to normal male baboons to determine its effect on platelet function in forming haemostatic plugs, and its capacity to prevent arteriovenous shunt and vascular graft thrombosis [2].
• 3 UK 37248 did not significantly alter the number of arrhythmias or the incidence of ventricular fibrillation resulting from coronary artery occlusion [3].

High impact information on UK 37248

• Both AH-P 719 and dazoxiben increased the level of cAMP in AA-stimulated platelets but again they were more effective in PRP from some individuals than others [4].
• In contrast, low concentrations of PGE2 added to the inhibition of platelet aggregation and increase in cyclic AMP levels induced by forskolin (which stimulates AC directly) and AH-P 719 and DN-9693 (which inhibit cyclic AMP phosphodiesterase (PDE] [5].
• 1 The effects of pretreatment with the thromboxane synthetase inhibitor UK 37248 (dazoxiben) administered 30 min before intravenous endotoxin (S. enteriditis) in the rat was investigated 2 Plasma prostaglandins and thromboxanes were determined via radioimmunoassay [1].
• 4 A further dose of 1 mg/kg UK 37248 was administered intravenously 5 min before the release of the 40 min coronary artery occlusion [3].
• 1 The effects of a selective thromboxane synthetase inhibitor, dazoxiben (UK 37248), on haemodynamics, eicosanoid levels, and lung vascular permeability were assessed in three unanesthetized goats with chronic lung lymph fistulae following infusions of E. coli endotoxin (1 microgram/kg) [6].

Biological context of UK 37248

• 1 In healthy male volunteers dazoxiben (UK 37248), an inhibitor of thromboxane synthetase, abolished the arterial and venous vasoconstriction produced in the forearm by cold stimulation [7].
• In vivo, administration of imidazole into the renal artery of the UUO kidney improved function slightly, whereas administration of UK 37248 or UK 38485 doubled renal blood flow and excretory function but did not restore them to normal [8].

Anatomical context of UK 37248

• Addition of the thromboxane synthetase inhibitor dazoxiben (UK 37248) 1 and 10 microM reduced adhesion to damaged blood vessel by about 45% at both concentrations, but did not affect adhesion to collagen-coated glass [9].
• The thromboxane-synthetase inhibitor UK 37248, inhibited both leukocyte aggregation and LDH release [10].

Analytical, diagnostic and therapeutic context of UK 37248

• 1 We have assessed the thromboxane synthetase inhibitor, dazoxiben (UK 37248), during dialysis in a double-blind, placebo-controlled crossover study [11].

References