NMDA receptor channels: Labeling of MK-801 with iodine-125 and fluorine-18

✍ Scribed by D.M. Wieland; M.R. Kilbourn; D.J. Yang; E. Laborde; D.L. Gildersleeve; M.E. van Dort; J-L. Pirat; B.J. Ciliax; A.B. Young

• Publisher: Elsevier Science
• Year: 1988
• Weight: 792 KB
• Volume: 39
• Category: Article
• ISSN: 0883-2889
• DOI: 10.1016/0883-2889(88)90103-7

✦ Synopsis

Methods for labeling the glutamate channel blocking agent MK-801 with iodine-125 ('*'I) and fluorine-18 ('*F) are described. Radioiodine was incorporated in the l-or 3-positions of the aromatic ring of (+)MK-801 by solid-state halogen exchange techniques. Attachment of the ['sF]fluoromethyl group to the bridgehead methyl position was achieved by reaction of ["Flfluoride with the triflamide alcohol 8 or the novel cyclic sulfamate 9 recently reported by Merck chemists. Radiochemical yields of (+)13-["F]fluoromethyl-MK-801 were >72%, EOB; radiochemical purity >99%. In competitive binding studies using rat brain homogenates, (f)3-bromo-MK-801 showed greater affinity than (+)MK-801 for the glutamate-linked channel. The experimental log P (2.1 k 0.1) of MK-801 is optimal for transit of the blood-brain barrier. These preliminary findings support further testing of 3-['231]iodo-MK-801 and ( &)13-['8F]fluoromethyl-MK-801 as possible agents for in oivo mapping of the glutamate receptor complex.