MEMANTINE EFFECTS ON SOMAN-INDUCED SEIZURES AND SEIZURE-RELATED BRAIN-DAMAGE

Excitatory amino acids have been implicated in the seizures and seizur e-related brain damage (SRBD) resulting from soman intoxication. Meman tine (Mem) is an open channel blocker of the glutaminergic NMDA recept or subtype reported to have anticonvulsant activity against soman. The aim of the present experiments was to evaluate the effect of Mem on e lectrographic seizure activity (EGSA) and SRBD produced by soman. Male rats were implanted with cortical screw electrodes for recording bipo lar electrocorticograms and allowed to recover for 5-7 days. EGSA was precipitated by injecting soman (180 mu g/kg, SC) 30 min after HI6 (12 5 mg/kg, IP) pretreatment. Saline, Mem (18 mg/kg), atropine (A;10 mg/k g), or Mem + A was administered IP either 5 or 40 min after the onset of EGSA. Saline-treated animals displayed limbic convulsive behaviors and EGSA lasting for 4 or more hours. Mem or Mem + A suppressed behavi oral signs of soman intoxication, but did not terminate EGSA or preven t SRBD. These results indicate that soman-induced seizures are not ame liorated by Mem or Mem + A, and that the presence or absence of soman- induced seizures cannot be verified reliably through behavioral observ ations alone.