Beta-proline analogues as agonists at the strychnine-sensitive glycine receptor

J Med Chem. 1992 Jan 24;35(2):233-41. doi: 10.1021/jm00080a006.

Abstract

3-Carboxy-3,4-dehydropyrrolidine was found to bind with affinity equal to that of glycine in a [3H]strychnine binding assay. Simple substitution of the 1-, 2-, 4-, or 5-position resulted in marked loss of affinity. A decline in affinity was also found upon enlargement, contraction, or saturation of the 5-membered ring. However, beta-proline and azetidine-3-carboxylic acid retained significant binding affinity. Despite its good affinity in [3H]strychnine binding, 3-carboxy-3,4-dehydropyrrolidine showed only weak agonist activity in intracellular recordings of cultured murine spinal cord neurons. This apparent lack of correlation between binding and functional results is discussed in light of the current models of the strychnine-sensitive glycine receptor.

MeSH terms

  • Animals
  • Binding, Competitive
  • Glycine / metabolism*
  • In Vitro Techniques
  • Membrane Potentials / drug effects
  • Mice
  • Proline / analogs & derivatives*
  • Proline / chemical synthesis
  • Proline / metabolism
  • Proline / pharmacology
  • Rats
  • Receptors, GABA-A / drug effects
  • Receptors, Glycine
  • Receptors, Neurotransmitter / drug effects*
  • Receptors, Neurotransmitter / metabolism
  • Spinal Cord / metabolism
  • Strychnine / metabolism
  • beta-Alanine / metabolism

Substances

  • Receptors, GABA-A
  • Receptors, Glycine
  • Receptors, Neurotransmitter
  • beta-Alanine
  • Proline
  • Strychnine
  • Glycine
  • beta-proline