Regular Article| Volume 9, ISSUE 8, P537-543, December 2000

A placebo-controlled, double-blind cross-over trial of adjunctive one month remacemide hydrochloride treatment in patients with refractory epilepsy

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      The efficacy, safety and pharmacokinetics of adjunctive remacemide hydrochloride, a novel, low-affinity non-competitive NMDA receptor channel blocker, were investigated in 28 adult patients with refractory epilepsy. This was a randomized double-blind placebo-controlled cross-over study with five 4-week periods (baseline, treatment 1, washout, treatment 2, washout). Baseline median seizure frequency was reduced by 33% following adjunctive remacemide hydrochloride 150 mg q.i.d. for 4 weeks compared with placebo (P= 0.041). Seizure frequency was reduced by ≥50% in 30% of patients treated with remacemide hydrochloride compared with 9% on placebo. Mean plasma concentration of concomitant carbamazepine increased by approximately 15% following adjunctive remacemide hydrochloride. There was no correlation between increased plasma carbamazepine and reduced seizure frequency. Remacemide hydrochloride was well tolerated and only three patients withdrew due to adverse events (two remacemide hydrochloride, one placebo). Two patients died unexpectedly from their epilepsy during placebo treatment; both deaths were considered by the investigators to be unrelated to earlier remacemide hydrochloride treatment. This first specific efficacy investigation with adjunctive remacemide hydrochloride demonstrated anticonvulsant effects in patients with refractory epilepsy. More extensive clinical investigation is justified.




        • Palmer G.C.
        • Harris E.W.
        • Ray R.
        • Stagnitto M.L.
        • Schmiesing R.J.
        Classification of compounds for prevention of NMDLA-induced seizures/mortality, or maximal electroshock and pentylenetetrazol seizures in mice and antagonism of MK801 binding in vitro.
        Archives Internationales de Pharmacodynamie et de Therapie. 1992; 317: 16-34
        • Clark B.
        • Hutchison J.B.
        • Jamieson V.
        • Jones T.
        • Palmer G.C.
        • Scheyer R.D.
        Potential antiepileptic drugs. Remacemide Hydrochloride.
        in: Levy R.H. Mattson R.H. Meldrum B. Antiepileptic Drugs. Raven Press Ltd, 4thEdition: New York1995: 1035-1044
        • Leach J.P.
        • Blacklaw J.
        • Jamieson V.
        • Jones T.
        • Richens A.
        • Brodie M.J.
        Mutual interaction between remacemide hydrochloride and carbamazepine two drugs with active metabolites.
        Epilepsia. 1996; 37: 1100-1106
      1. Epilepsia. 1981; 22: 489-501
        • Koch G.G.
        The use of non-parametric methods in the statistical analysis of a two-period changeover design.
        Biometrics. 1972; 5: 577-584
        • Leestma J.E.
        • Kelelkar M.B.
        • Teas J.J.
        • Jay G.W.
        • Hughes J.R.
        Sudden unexpected death associated with seizures.
        Journal of Neurology, Neuropsychology and Psychiatry. 1984; 25: 84-88
        • Schaeder P.L.
        • Lathers C.M.
        Paroxysmal autonomic dysfunction, epileptogenic activity and sudden death.
        Epilepsy Research. 1989; 3: 55-62