Document Detail


Synthesis and anticonvulsant activity of N,N-phthaloyl derivatives of central nervous system inhibitory amino acids.
MedLine Citation:
PMID:  11759171     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Archiv der Pharmazie     Volume:  334     ISSN:  0365-6233     ISO Abbreviation:  Arch. Pharm. (Weinheim)     Publication Date:  2001 Oct 
Date Detail:
Created Date:  2001-12-10     Completed Date:  2002-01-22     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0330167     Medline TA:  Arch Pharm (Weinheim)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  323-31     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutical Chemistry, University of Jena, Philosophenweg 14, 07743 Jena, Germany.
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MeSH Terms
Descriptor/Qualifier:
Amino Acids / chemical synthesis*,  pharmacology*
Animals
Anticonvulsants / chemical synthesis*,  pharmacology*
Chemistry, Physical
Convulsants / pharmacology
Electroshock
Indicators and Reagents
Mice
Pentylenetetrazole / antagonists & inhibitors,  pharmacology
Phthalic Acids / chemical synthesis*,  pharmacology*
Physicochemical Phenomena
Structure-Activity Relationship
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Anticonvulsants; 0/Convulsants; 0/Indicators and Reagents; 0/Phthalic Acids; 54-95-5/Pentylenetetrazole

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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