PHARMACOLOGICAL PROTECTION OF CNS WHITE-MATTER DURING ANOXIA - ACTIONS OF PHENYTOIN, CARBAMAZEPINE AND DIAZEPAM

The effects of phenytoin (DPH), carbamazepine (CBZ) and diazepam (DZP) on anoxia-induced injury in CNS white matter were studied using the i n vitro rat optic nerve preparation. Optic nerves were subjected to 60 min of anoxia and functional recovery was assessed using the area und er the compound action potential. Under normoxic conditions, applicati on of DPH, CBZ and DZP reduced compound action potential area over con centration ranges known to block sodium channels. All three compounds, however, protected against anoxic injury at concentrations below thos e that inhibited the normoxic compound action potential. Thus, the app lication of 1 muM DPH, CBZ or DZP during anoxia resulted in compound a ction potential recovery to 60.0, 53.8 and 69.2% of control, respectiv ely, compared to compound action potential recovery of 34.8% in the ab sence of drugs (P < .05 in all three cases). In the cases of CBZ and D PH, 60% improvement in recovery from anoxia was produced by concentrat ions well below those employed clinically to treat epilepsy, suggestin g a potential role for these drugs in the protection of CNS white matt er from anoxic injury.