Comparison of Two Ester Prodrugs of Methylprednisolone on Early Neurologic Recovery in a Murine Closed Head Injury Model

In prior work, methylprednisolone succinate, sodium salt (MPSS) has been shown to enhance the early neurologic recovery of moderately or severely head-injured mice. In the present study, the relative cerebroprotective potency and efficacy of MPSS was compared to another methylprednisolone ester prodrug, methylprednisolone suleptanate, sodium salt (U67590A). Male CF-1 mice received a 900 g-cm concussive head injury followed within 5 min by an intravenous bolus dose of vehicle, MPSS, or U67590A. At 1 h postinjury, the neurologic status was evaluated blindly using a grip test. Both methylprednisolone esters were found to enhance early neurologic recovery after this severe head injury. However, U67590A was four to eight times more potent than MPSS. Either a 7.5 or 15.0 mg/kg dose of U67590A produced a significant improvement in recovery while a 60.0 mg/kg dose of MPSS was required. The maximal efficacy of the two prodrugs was equal. These results indicate that the ester of methylprednisolone can greatly influence the steroid's cerebroprotective potency and that U67590A may be superior in this regard to MPSS for the acute treatment of CNS injury.