Synthesis and receptor binding studies of (+/-)1-iodo-MK-801

Journal Article · Thu Jun 01 00:00:00 EDT 1989 · Pharmaceutical Research; (USA)

DOI:https://doi.org/10.1023/A:1015912322247· OSTI ID:5546193

Yang, D J; Ciliax, B J; Van Dort, M E; Gildersleeve, D; Pirat, J L; Young, A B; Wieland, D M ^[1]

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1. Univ. of Michigan Medical School, Ann Arbor (USA)

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 (+/)1-iodo-MK-801 and (+/-)1-({sup 125}I)iodo-MK-801. The effect of (+/-)1-iodo-MK-801 on ligand binding to the NMDA-linked glutamate receptor site was assessed using a rat brain homogenate assay. (+/-)1-Iodo-MK-801 displaced the dissociative anesthetic ligand ({sup 3}H)N-(1-(2-thienyl)cyclohexyl)piperidine (({sup 3}H)TCP) binding with an IC50 of 1 microM, 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 (+/-)1-iodo-MK-801 in rat brain. These results suggest that (+/-)1-iodo-MK-801 may not be a suitable ligand for mapping NMDA-linked glutamate receptor channels.

• OSTI ID: 5546193
• Journal Information: Pharmaceutical Research; (USA), Vol. 6:6; ISSN 0724-8741
• Country of Publication: United States
• Language: English

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62 RADIOLOGY AND NUCLEAR MEDICINE
ASPARTIC ACID
BIOCHEMICAL REACTION KINETICS
GLUTAMIC ACID
RECEPTORS
RADIOPHARMACEUTICALS
CHEMICAL PREPARATION
ANTICONVULSANTS
AUTORADIOGRAPHY
BRAIN
LIGANDS
NERVES
RATS
SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY
AMINO ACIDS
ANIMALS
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CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM DEPRESSANTS
COMPUTERIZED TOMOGRAPHY
DIAGNOSTIC TECHNIQUES
DRUGS
EMISSION COMPUTED TOMOGRAPHY
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PROTEINS
REACTION KINETICS
RODENTS
SYNTHESIS
TOMOGRAPHY
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