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

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, beta-alanine and gamma-aminobutyric acid (GABA) derivatives were synthesized. The corresponding taurine derivatives were also included. Generally, the glycine-derived amides showed a higher activity than the beta-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 ED50 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.

• Authors: C O Usifoh, D M Lambert, J Wouters, G K Scriba
• Journal: Archiv der Pharmazie (Arch Pharm (Weinheim)) Vol. 334 Issue 10 Pg. 323-31 (Oct 2001) ISSN: 0365-6233 [Print] Germany
• PMID: 11759171 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acids
• Anticonvulsants
• Convulsants
• Indicators and Reagents
• Phthalic Acids
• Pentylenetetrazole

Topics

• Amino Acids (chemical synthesis, pharmacology)
• Animals
• Anticonvulsants (chemical synthesis, pharmacology)
• Chemical Phenomena
• Chemistry, Physical
• Convulsants (pharmacology)
• Electroshock
• Indicators and Reagents
• Mice
• Pentylenetetrazole (antagonists & inhibitors, pharmacology)
• Phthalic Acids (chemical synthesis, pharmacology)
• Structure-Activity Relationship