The excitatory amino acid antagonist d-CPP-ene (SDZ EAA-494) in patients with epilepsy

S. Sveinbjornsdottir, J. W A S Sander, D. Upton, P. J. Thompson, P. N. Patsalos, D. Hirt, M. Emre, D. Lowe, J. S. Duncan

Research output: Contribution to journalArticle

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Abstract

The amino acids l-glutamate and l-aspartate have been shown to be excitatory neurotransmitters in mammalian central nervous systems. Antagonists acting selectively at excitatory amino acid receptors have shown antiepileptic properties in several animal models. We report the results of the first therapeutic trial of the competitive NMDA antagonist, d-CPP-ene (SDZ EAA-494), in eight patients with intractable complex partial seizures. All patients withdrew prematurely because of side-effects, including poor concentration (8), sedation (7), ataxia (6), depression (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 partial status epilepticus on withdrawal of dCPP-ene. EEG on treatment (5) or in the immediate post-treatment period (2) showed slowing of background activity and, in five cases, an increase in epileptiform activity. 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 patients with refractory partial seizures is not promising. Evaluation of related compounds is warranted.

Original languageEnglish
Pages (from-to)165-174
Number of pages10
JournalEpilepsy Research
Volume16
Issue number2
DOIs
Publication statusPublished - 1993
Externally publishedYes

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Excitatory Amino Acid Antagonists
Epilepsy
Seizures
Athetosis
Sturge-Weber Syndrome
Dysarthria
Amnesia
Status Epilepticus
Glutamate Receptors
N-Methylaspartate
Ataxia
Serum
Aspartic Acid
Anticonvulsants
Neurotransmitter Agents
SDZ EAA 494
3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
Glutamic Acid
Electroencephalography
Therapeutics

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Sveinbjornsdottir, S., Sander, J. W. A. S., Upton, D., Thompson, P. J., Patsalos, P. N., Hirt, D., ... Duncan, J. S. (1993). The excitatory amino acid antagonist d-CPP-ene (SDZ EAA-494) in patients with epilepsy. Epilepsy Research, 16(2), 165-174. https://doi.org/10.1016/0920-1211(93)90031-2
Sveinbjornsdottir, S. ; Sander, J. W A S ; Upton, D. ; Thompson, P. J. ; Patsalos, P. N. ; Hirt, D. ; Emre, M. ; Lowe, D. ; Duncan, J. S. / The excitatory amino acid antagonist d-CPP-ene (SDZ EAA-494) in patients with epilepsy. In: Epilepsy Research. 1993 ; Vol. 16, No. 2. pp. 165-174.
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Sveinbjornsdottir, S, Sander, JWAS, Upton, D, Thompson, PJ, Patsalos, PN, Hirt, D, Emre, M, Lowe, D & Duncan, JS 1993, 'The excitatory amino acid antagonist d-CPP-ene (SDZ EAA-494) in patients with epilepsy', Epilepsy Research, vol. 16, no. 2, pp. 165-174. https://doi.org/10.1016/0920-1211(93)90031-2

The excitatory amino acid antagonist d-CPP-ene (SDZ EAA-494) in patients with epilepsy. / Sveinbjornsdottir, S.; Sander, J. W A S; Upton, D.; Thompson, P. J.; Patsalos, P. N.; Hirt, D.; Emre, M.; Lowe, D.; Duncan, J. S.

In: Epilepsy Research, Vol. 16, No. 2, 1993, p. 165-174.

Research output: Contribution to journalArticle

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AU - Sveinbjornsdottir, S.

AU - Sander, J. W A S

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AU - Thompson, P. J.

AU - Patsalos, P. N.

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AU - Duncan, J. S.

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Sveinbjornsdottir S, Sander JWAS, Upton D, Thompson PJ, Patsalos PN, Hirt D et al. The excitatory amino acid antagonist d-CPP-ene (SDZ EAA-494) in patients with epilepsy. Epilepsy Research. 1993;16(2):165-174. https://doi.org/10.1016/0920-1211(93)90031-2