Synthesis and pharmacological study of some new beta-(dialkylaminomethyl)- gamma-butyrolactones and their tetrahydrofuran analogues

Farmaco. 1996 Jan;51(1):19-26.

Abstract

This paper describes the synthesis of beta-(dialkylaminomethyl)-gamma- butyrolactones (6 and 15) and their tetrahydrofuran analogs 7 and 16. Their convulsant activity was studied on mice and could display an antiGABAergic component, but, unlike the alpha-(dialkylaminomethyl)- gamma-butyrolactones, no antiglycinergic component was detected. The possibility of an activation of the glutamatergic receptors (NMDA), by indirect stimulation of their glycinergic site, by the tetrahydrofurans analogs 7 could be considered. These compounds exhibited, at low doses (1/3 to 1/20 of their convulsant doses), an anticonvulsant action in the maximal electroshock test and this is in agreement with the abovementioned possibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / chemical synthesis
  • 4-Butyrolactone / pharmacology
  • Animals
  • Atropine / pharmacology
  • Convulsants / chemical synthesis*
  • Convulsants / pharmacology
  • Epilepsy, Tonic-Clonic / chemically induced
  • Excitatory Amino Acid Agonists / chemical synthesis*
  • Excitatory Amino Acid Agonists / pharmacology
  • Glycine Agents / chemical synthesis*
  • Glycine Agents / pharmacology
  • Male
  • Mice
  • Mice, Inbred NZB
  • Muscarinic Antagonists / pharmacology
  • Rats

Substances

  • Convulsants
  • Excitatory Amino Acid Agonists
  • Glycine Agents
  • Muscarinic Antagonists
  • Atropine
  • 4-Butyrolactone