γ‐aminobutyric acid uptake inhibition and anticonvulsant activity of nipecotic acid esters

A. Michael Crider, J. D. Wood, Kathryn D. Tschappat, Christine N. Hinko, Karen Seibert

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

n‐Alkyl esters of nipecotic acid were prepared by Fischer esterification, and the esters were evaluated against bicuculline‐induced seizures in mice. Evaluation of the alkyl esters for inhibition of γ‐aminobutyric acid uptake into mouse whole brain mini‐slices revealed that the order of potency was proportional to chain length. The octyl ester inhibited γ‐aminobutyric acid and β‐alanine uptakes by apparently nonspecific mechanisms. A variety of phenyl esters of nipecotic acid were also synthesized utilizing either dicyclohexylcarbodiimide or 1,1′‐carbonyldiimidazole as the condensing agent. Most of the phenyl esters were potent inhibitors of γ‐aminobutyric acid uptake. The uptake inhibition appeared to involve specific and nonspecific (detergent‐like) mechanisms. The m‐nitrophenyl and p‐nitrophenyl esters were particularly potent against bicuculline‐induced seizures in mice.

Original languageEnglish
Pages (from-to)1612-1616
Number of pages5
JournalJournal of Pharmaceutical Sciences
Volume73
Issue number11
DOIs
StatePublished - Nov 1984

Keywords

  • Anticonvulsant agents—potential, nipecotic acid esters, synthesis
  • Nipecotic acid esters—synthesis, anticonvulsant activity

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