The effects of oral and intravenous direct thrombin inhibitors on the sizeof photochemically induced cortical infarction in rats

Oral thrombin inhibitors are under development as potential drugs for proph ylaxis and treatment of thrombotic events. The effect of pretreatment with two direct thrombin inhibitors, melagatran and inogatran, was evaluated in a rat model of cerebral infarction. Ischaemic stroke was induced by photoch emical reaction after an injection of Rose Bengal and focused posterior and to the right of the intersection of the coronal and sagittal sutures on th e intact calvarium. A single oral dose of melagatran (30 mu mol/kg) signifi cantly reduced the volume of the cortical infarct by 53% (P <.05) compared with control. In addition, following intravenous inogatran (6 <mu>mol/kg) o r oral inogatran (100 mu mol/kg), the volume of the cortical infarct decrea sed by 83% and 19%, respectively, compared with control. This study showed that experimental focal ischaemic infarction, elicited by photochemically i nduced endothelial cell damage, can be significantly reduced with melagatra n and inogatran, direct thrombin inhibitors. (C) 2001 Elsevier Science Ltd. All rights reserved.