Two prodrugs of potent and selective GluR5 kainate receptor antagonists actives in three animal models of pain

J Med Chem. 2005 Jun 30;48(13):4200-3. doi: 10.1021/jm0491952.

Abstract

Amino acids 5 and 7, two potent and selective competitive GluR5 KA receptor antagonists, exhibited high GluR5 receptor affinity over other glutamate receptors. Their ester prodrugs 6 and 8 were orally active in three models of pain: reversal of formalin-induced paw licking, carrageenan-induced thermal hyperalgesia, and capsaicin-induced mechanical hyperalgesia.

MeSH terms

  • Amino Acids / pharmacology*
  • Analgesics / chemistry*
  • Analgesics / pharmacokinetics
  • Analgesics / pharmacology*
  • Animals
  • Biological Availability
  • Cell Line
  • Disease Models, Animal
  • Humans
  • Hyperalgesia / drug therapy
  • Pain / drug therapy*
  • Rats
  • Receptors, AMPA / metabolism
  • Receptors, Kainic Acid / antagonists & inhibitors*
  • Recombinant Proteins / metabolism
  • Spinal Cord / physiopathology
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / metabolism

Substances

  • Amino Acids
  • Analgesics
  • Gluk1 kainate receptor
  • Receptors, AMPA
  • Receptors, Kainic Acid
  • Recombinant Proteins
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid