Synthesis and anticonvulsant activity of N,N-phthaloyl derivatives of central nervous system inhibitory amino acids

Cyril O. Usifoh, Didier M. Lambert, Johan Wouters, Gerhard K E Scriba

Résultats de recherche: Contribution à un journal/une revueArticleRevue par des pairs

Résumé

In order to study the influence of the length of the amino acid chain of N,N-phthaloyl-amino acid amides as analogues of the former anticonvulsant taltrimide on the seizure-antagonizing activity glycine, β-alanine and γ-aminobutyric acid (GABA) derivatives were synthesized. The corresponding taurine derivatives were also included. Generally, the glycine-derived amides showed a higher activity than the β-alanine and GABA derivatives in the maximal electroshock seizure (MES) test in mice upon intraperitoneal administration. The activity was comparable to the respective taurine derivatives. The N,N-phthaloyl-glycine amides were also active in the MES test upon oral administration to rats. No significant activity was noted in the seizure threshold test with subcutaneous pentylene-tetrazole. The ED 50 of N,N-phthaloyl-glycine ethyl amide (4b) in the MES test upon intraperitoneal administration to mice was 19.1 mg/kg. On a molar basis this activity is comparable to the activity of phenytoin with little toxicity in the rotorod test. In conclusion, N,N-phthaloyl-glycine amides might represent promising antiepileptic drugs.

langue originaleAnglais
Pages (de - à)323-331
Nombre de pages9
journalArchiv der Pharmazie
Volume334
Numéro de publication10
Les DOIs
Etat de la publicationPublié - 3 déc. 2001

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