A primate model for testing anticonvulsant drugs

Abstract

Senegalese baboons (Papio papio), with a natural syndrome of photosensitive epilepsy, consistently show generalized myoclonic jerks if stimulated stroboscopically at hourly intervals, two to eight hours after the intravenous administration of allylglycine, 200 mg/kg. This provides a model for testing the acute antiepileptic effects of established or new drugs. The relationship between concentration of drug, antiepileptic action, and acute neurological toxic effects can be studied. Pnehobarbital (15 mg/kg) and diazepam (0;5 to 1.5 mg/kg) were highly effective in the absence of signs of toxic reaction (plasma levels: phenobarbital sodium, 0.7 to 1.7 mg/100 ml; diazepam, greater than 0.5 mug/ml). After administration of carbamazepine (30 to 40 mg/kg) and diphenylhydantoin sodium (40 to 50 mg/kg), antiepileptic action was seen, but was accompanied by severe toxic signs (nystagmus and ataxia). Sulthiame (20 to 125 mg/kg) and ethosuximide (50 to 100 mg/kg) had little antiepileptic activity and no acute toxic effects. This primate model may aid the identification of new drugs that are active against grand mal seizures and status epilepticus.