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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)323-331
Number of pages9
JournalArchiv der Pharmazie
Volume334
Issue number10
DOIs
Publication statusPublished - 3 Dec 2001

Keywords

  • β-Alanine
  • γ-Aminobutyric acid
  • Anticonvulsants
  • Glycine
  • N,N-Phthaloyl-amino acids

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