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A primate model for testing anticonvulsant drugs.

B S Meldrum, BChir, R W Horton

    Archives of Neurology
    |May 1, 1975
    PubMed
    Summary
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    Senegalese baboons with epilepsy provide a model for testing antiepileptic drugs. Phenobarbital and diazepam showed effectiveness without toxicity, unlike other tested antiepileptic medications.

    Area of Science:

    • Neuroscience
    • Pharmacology

    Background:

    • Senegalese baboons (Papio papio) exhibit a natural photosensitive epilepsy syndrome.
    • Stroboscopic stimulation reliably induces generalized myoclonic jerks in these baboons post-allylglycine administration.

    Purpose of the Study:

    • To establish a primate model for evaluating acute antiepileptic drug effects.
    • To investigate the relationship between drug concentration, efficacy, and neurological toxicity.

    Main Methods:

    • Allylglycine (200 mg/kg) administered intravenously to induce epilepsy in baboons.
    • Stroboscopic stimulation used to elicit myoclonic jerks.
    • Testing of phenobarbital, diazepam, carbamazepine, diphenylhydantoin sodium, sulthiame, and ethosuximide for antiepileptic activity and toxicity.

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    Main Results:

    • Phenobarbital (15 mg/kg) and diazepam (0.5–1.5 mg/kg) were highly effective with no observed toxicity.
    • Carbamazepine and diphenylhydantoin sodium showed antiepileptic action but caused severe toxic signs (nystagmus, ataxia).
    • Sulthiame and ethosuximide exhibited minimal antiepileptic activity and no acute toxicity.

    Conclusions:

    • This baboon model is effective for assessing acute antiepileptic drug effects and toxicity.
    • Phenobarbital and diazepam demonstrate a favorable therapeutic profile in this model.
    • The model holds potential for identifying novel drugs for grand mal seizures and status epilepticus.