(+)-3-[123I]Iodo-MK-801: synthesis and characterization of binding to the N-methyl-D-aspartate receptor complex

Life Sci. 1990;46(15):1103-10. doi: 10.1016/0024-3205(90)90420-v.

Abstract

Synthetic methods have been established for preparing high specific activity (+)-3-[123I]Iodo-MK-801 in high radiochemical yield. The binding of the radiotracer to rat cortical membranes has been examined to assess its potential use as an in vivo imaging agent for the N-methyl-D-aspartate (NMDA) receptor-ion channel complex. Under the conditions of the assay, specific (+)-3-[123I]Iodo-MK-801 binding to membrane homogenates represented greater than 95% of the total binding. Several structurally distinct, noncompetitive NMDA receptor antagonists inhibited binding with potencies in accordance with their reported inhibitory activity at the receptor complex. The concentration of (+/-)-3-Iodo-MK-801 required to inhibit 50% of (+)-3-[123I]Iodo-MK-801 binding (IC50) was 3.4 nM when using a low ionic strength assay buffer and 5.5 nM in a physiological buffer. In a thoroughly washed membrane preparation, (+)-3-[123I]Iodo-MK-801 binding was enhanced by L-glutamate and glycine at concentrations known to activate the NMDA receptor. The results indicate that (+)-3-[123I]Iodo-MK-801 specifically labels the NMDA receptor complex in rat brain membranes and the retention of high affinity under near physiological assay conditions suggests that it may be useful as a SPECT imaging agent for the receptor in vivo.

MeSH terms

  • Animals
  • Brain / diagnostic imaging
  • Brain / drug effects
  • Brain / metabolism*
  • Cell Membrane / diagnostic imaging
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Chemical Phenomena
  • Chemistry
  • Chromatography, High Pressure Liquid
  • Dibenzocycloheptenes / metabolism*
  • Dizocilpine Maleate* / analogs & derivatives*
  • In Vitro Techniques
  • Iodine Radioisotopes
  • Male
  • Rats
  • Rats, Inbred Strains
  • Receptors, Amino Acid*
  • Receptors, Cell Surface / drug effects
  • Receptors, Cell Surface / metabolism*
  • Tomography, Emission-Computed

Substances

  • Dibenzocycloheptenes
  • Iodine Radioisotopes
  • Receptors, Amino Acid
  • Receptors, Cell Surface
  • aspartic acid receptor
  • 1-iodo-MK 801
  • Dizocilpine Maleate