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

Oral thrombin inhibitors are under development as potential drugs for prophylaxis 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 photochemical reaction after an injection of Rose Bengal and focused posterior and to the right of the intersection of the coronal and sagittal sutures on the intact calvarium. A single oral dose of melagatran (30 μmol/kg) significantly reduced the volume of the cortical infarct by 53% (P<.05) compared with control. In addition, following intravenous inogatran (6 μmol/kg) or oral inogatran (100 μmol/kg), the volume of the cortical infarct decreased by 83% and 19%, respectively, compared with control. This study showed that experimental focal ischaemic infarction, elicited by photochemically induced endothelial cell damage, can be significantly reduced with melagatran and inogatran, direct thrombin inhibitors.