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 in vitro rat optic nerve preparation. Optic nerves were subjected to 60 min of anoxia and functional recovery was assessed using the area under the compound action potential. Under normoxic conditions, application of DPH, CBZ and DZP reduced compound action potential area over concentration ranges known to block sodium channels. All three compounds, however, protected against anoxic injury at concentrations below those that inhibited the normoxic compound action potential. Thus, the application of 1 microM DPH, CBZ or DZP during anoxia resulted in compound action potential recovery to 60.0, 53.8 and 69.2% of control, respectively, compared to compound action potential recovery of 34.8% in the absence of drugs (P < .05 in all three cases). In the cases of CBZ and DPH, 60% improvement in recovery from anoxia was produced by concentrations well below those employed clinically to treat epilepsy, suggesting a potential role for these drugs in the protection of CNS white matter from anoxic injury.
Fern
R
R
Department of Neurology, Yale University School of Medicine, New Haven, CT 06510.
Ransom
B R
BR
Stys
P K
PK
Waxman
S G
SG
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001369:Axons / Q000187:drug effects*; D002220:Carbamazepine / Q000627:therapeutic use*; D003975:Diazepam / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D000860:Hypoxia / Q000150:complications* / Q000188:drug therapy; D009900:Optic Nerve / Q000187:drug effects* / Q000502:physiology; D009901:Optic Nerve Diseases / Q000209:etiology / Q000517:prevention & control*; D010672:Phenytoin / Q000627:therapeutic use*; D051381:Rats
D002220:Carbamazepine; D010672:Phenytoin; D003975:Diazepam