D,L-(tetrazol-5-yl) glycine: a novel and highly potent NMDA receptor agonist

Eur J Pharmacol. 1991 Oct 15;203(2):237-43. doi: 10.1016/0014-2999(91)90719-7.


This paper describes the pharmacological activity of D,L-(tetrazol-5-yl)glycine, a structurally novel and highly potent agonist at the N-methyl-D-aspartate (NMDA) subtype of excitatory amino acid receptor. D,L-(Tetrazol-5-yl)glycine potently displaced NMDA receptor binding to rat brain membranes as measured using [3H]CGS19755 (IC50 = 98 +/- 7 nM) and [3H]glutamate (IC50 = 36 +/- 18 nM) as ligands. D,L-(Tetrazol-5-yl)glycine did not appreciably inhibit the binding of D,L-alpha-[5-methyl-3H] amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), [3H]kainate, or [3H]glycine (IC50s greater than 30,000 nM). D,L-(Tetrazol-5-yl)glycine was more potent than NMDA or cis-methanoglutamate as a depolarizing agent in the rat cortical slice, and unlike these other agents induced rapid receptor-mediated neurotoxicity. Depolarization by D,L-(tetrazol-5-yl)glycine was antagonized by LY233053, a selective NMDA receptor antagonist. D,L-(Tetrazol-5-yl)glycine was a highly potent convulsant when given to neonatal rats (ED50 = 0.071 mg/kg i.p.). Convulsions in neonatal rats or lethality in mice induced by D,L-(tetrazol-5-yl)glycine were selectively antagonized by competitive and non-competitive NMDA receptor antagonists. D,L-(Tetrazol-5-yl)glycine is a structurally novel (tetrazole-substituted) compound that is a highly potent and selective NMDA receptor agonist. D,L-(Tetrazol-5-yl)glycine could be used to probe further NMDA receptor function in vitro and in vivo.

MeSH terms

  • Animals
  • Binding, Competitive
  • Cerebral Cortex / anatomy & histology
  • Cerebral Cortex / drug effects
  • Glutamates / metabolism
  • Glutamic Acid
  • Glycine / analogs & derivatives*
  • Glycine / metabolism
  • Glycine / pharmacology
  • Kinetics
  • Male
  • Pipecolic Acids / metabolism
  • Rats
  • Rats, Inbred Strains
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Seizures / chemically induced
  • Tetrazoles / metabolism
  • Tetrazoles / pharmacology*
  • Tritium


  • Glutamates
  • Pipecolic Acids
  • Receptors, N-Methyl-D-Aspartate
  • Tetrazoles
  • Tritium
  • (tetrazol-5-yl)glycine
  • Glutamic Acid
  • selfotel
  • Glycine