Evaluating of the Anticonvulsant Gabapentin against Nerve Agent-Induced Seizures in a Guinea Pig Model

摘要

Gabapentin is an anticonvulsant drug approved by the FDA as an adjunctive medication to control partial seizures, and recently has been approved for treating neuropathic pain. This study evaluated whether gabapentin could terminate or moderate nerve agent-induced seizures using a validated guinea pig model. Male Hartley guinea pigs were surgically prepared to record electroencephalographic (EEG) activity. After a week recovery, animals were pretreated with pyridostigmine 30 min prior to subcutaneous soman challenge (56 ug/kg; 2 X LD50). One min later, animals were administered atropine sulfate + 2- pralidoxime chloride. EEG activity was recorded continuously for 5 hr after exposure and 30 min the next day. This regimen elicits status epilepticus seizures in 100% of animals with a latency of approx. 7 min. Gabapentin in doses from 3.2 - 180.0 mg/kg failed to control seizure activity when administered as a therapy at seizure onset. When given as a pretreatment 30 min before soman exposure, seizures were prevented or suppressed in a dose- dependent fashion. Gabapentin possesses some anticonvulsant properties against these seizures when administered as a pretreatment, but high dose requirements and potential side effects make this impractical. Gabapentin and compounds of this class show little promise as a replacement treatment for nerve agent- induced seizures.