THE EXCITATORY AMINO-ACID ANTAGONIST D-CPP-ENE (SDZ EAA-494) IN PATIENTS WITH EPILEPSY

The amino acids L-glutamate and L-aspartate have been shown to be exci tatory neurotransmitters in mammalian central nervous systems. Antagon ists acting selectively at excitatory amino acid receptors have shown antiepileptic properties in several animal models. We report the resul ts of the first therapeutic trial of the competitive NMDA antagonist, D-CPP-ene (SDZ EAA-494), in eight patients with intractable complex pa rtial seizures. All patients withdrew prematurely because of side-effe cts, including poor concentration (8), sedation (7), ataxia (6), depre ssion (3), dysarthria (2), amnesia (2) and unilateral choreo-athetosis in a patient with contralateral Sturge-Weber syndrome. Seizures were unchanged in four patients and worse in three. A further patient with apparent improvement in seizures in the first week developed complex p artial status epilepticus on withdrawal of DCPP-ene. EEG on treatment (5) or in the immediate post-treatment period (2) showed slowing of ba ckground activity and, in five cases, an increase in epileptiform acti vity. Serum concentrations of DCPP-ene were found to be unpredictable and higher than expected from pharmacokinetic data on normal subjects. There was no clear relationship between serum concentrations and the severity of side-effects. Preliminary experience with DCPP-ene in pati ents with refractory partial seizures is not promising. Evaluation of related compounds is warranted.