Synthesis, radiolabelling and biological characterization of (D)-7-iodo-N-(1-phosphonoethyl)-5-aminomethylquinoxaline-2,3-dione, a glycine-binding site antagonist of NMDA receptors

Bioorg Med Chem Lett. 2000 Jan 3;10(1):75-8. doi: 10.1016/s0960-894x(99)00576-4.

Abstract

(D)-7-Iodo-N-(1-phosphonoethyl)-5-aminomethylquinoxaline-2,3 -dione (I-PAMQX), is a potent, in vivo active antagonist acting at the glycine binding site of the NMDA receptor complex. Radioiodinated [131I]I-PAMQX was prepared with good yields and high specific activity from its 7-bromo analogue. Biodistribution studies of [131I]I-PAMQX in mice showed a relatively slow clearance from the blood. The uptake of radioactivity was highest in the kidneys, moderate in the heart, lung, liver and bones, and low in the brain.

MeSH terms

  • Animals
  • Anticonvulsants / chemical synthesis*
  • Anticonvulsants / pharmacokinetics
  • Anticonvulsants / pharmacology*
  • Binding Sites / drug effects
  • Female
  • Glycine / metabolism*
  • Inhibitory Concentration 50
  • Iodine Radioisotopes / chemistry
  • Kidney / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Organophosphonates / chemical synthesis*
  • Organophosphonates / metabolism
  • Organophosphonates / pharmacokinetics
  • Organophosphonates / pharmacology*
  • Quinoxalines / chemical synthesis*
  • Quinoxalines / metabolism
  • Quinoxalines / pharmacokinetics
  • Quinoxalines / pharmacology*
  • Radioligand Assay
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / pharmacology*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Substrate Specificity
  • Tissue Distribution

Substances

  • 7-iodo-N-(1-phosphonoethyl)-5-aminomethylquinoxaline-2,3-dione
  • Anticonvulsants
  • Iodine Radioisotopes
  • Organophosphonates
  • Quinoxalines
  • Radiopharmaceuticals
  • Receptors, N-Methyl-D-Aspartate
  • Glycine