Chemotherapy of herpes simplex virus encephalitis in mice by direct intracerebral injection

The effects of 9-beta-D-arabinofuranosyladenine-5'-phosphate (ara-A-5'-P) on herpes simplex virus encephalitis in mice were studied. This drug is a monophosphate derivative of adenine arabinoside (ara-A). When administered by the intracerebral (ic) route, ara-A-5'-P was highly effective in virus-infected mice in the 17-20 g weight range provided therapy was begun before clinical symptoms of encephalitis appeared. The most effective dose schedule was found to be three daily ic injections totaling 400 micrograms/day (20 mg/kg) beginning on the third day after injection. Such treatment resulted in a survival rate of 50%-75% among infected mice after six months. In the early stages of many experiments, 90%-100% of the controls died whereas all of the treated animals survived.