Abstract
The glutamate analogue N-methyl-D-aspartate (NMDA) binds to a subset of glutamate receptors that are coupled to a voltage-sensitive cation channel. This NMDA-linked channel is the likely binding locus of the potent anticonvulsant MK-801. To develop single-photon emission computed tomography (SPECT) probes of this brain channel, we synthesized (±)l-iodo-MK-801 and (±)l-[125I]iodo-MK-801. The effect of (±)l-iodo-MK-801 on ligand binding to the NMDA-linked glutamate receptor site was assessed using a rat brain homogenate assay. (±)l-Iodo-MK-801 displaced the dissociative anesthetic ligand [3H]N-[l-(2-thienyl)cyclohexyl]piperidine ([3H]TCP) binding with an IC50 of 1 µM, which is a 10-fold lower binding affinity than that of (±)MK-801. In in vivo autoradiographic studies, (±)MK-801 failed to block selective uptake of (±)l-iodo-MK-801 in rat brain. These results suggest that (±)l-iodo-MK-801 may not be a suitable ligand for mapping NMDA-linked glutamate receptor channels.
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Yang, D.J., Ciliax, B.J., Van Dort, M.E. et al. Synthesis and Receptor Binding Studies of (±)l-Iodo-MK-801. Pharm Res 6, 474–476 (1989). https://doi.org/10.1023/A:1015912322247
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DOI: https://doi.org/10.1023/A:1015912322247