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Experimental anticonvulsant cinromide in monkey model: preliminary efficacy.

J S Lockard, R H Levy, L L DuCharme

    Epilepsia
    |August 1, 1979
    PubMed
    Summary
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    Cinromide shows promise as an anticonvulsant in a monkey model, effectively reducing seizures. Further research is planned to evaluate its efficacy via gastric administration.

    Area of Science:

    • Pharmacology
    • Neuroscience
    • Preclinical Research

    Background:

    • Cinromide (3-bromo-N-ethylcinnamide) is an experimental anticonvulsant.
    • The parent drug has a short half-life (1-2 hr) in monkeys, while its active metabolite (3-bromocinnamide) has a longer half-life (4-6 hr).

    Purpose of the Study:

    • To conduct a preliminary evaluation of Cinromide's anticonvulsant efficacy in an alumina-gel monkey model.
    • To determine the effective plasma concentration range of Cinromide's metabolite for seizure control.

    Main Methods:

    • Six chronically epileptic monkeys received intravenous infusions of Cinromide at varying concentrations.
    • Steady-state plasma levels of the drug and its metabolite were achieved and monitored.
    • Seizure activity and electroencephalogram (EEG) patterns were assessed during baseline and treatment periods.

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    Main Results:

    • Cinromide demonstrated efficacy in the monkey model at metabolite plasma concentrations of 7-14 micrograms/ml.
    • A significant decrease in generalized tonic-clonic seizures and EEG bursting was observed during Cinromide administration.
    • Minimal side effects were noted at effective plasma levels, though withdrawal seizures occurred upon drug cessation.

    Conclusions:

    • Cinromide is tentatively effective as an anticonvulsant in this preclinical monkey model.
    • The study suggests a therapeutic window for Cinromide's metabolite in managing seizures.
    • Further investigation, including oral administration, is warranted to fully assess Cinromide's therapeutic potential.