title: NMDA receptor channels: labeling of MK-801 with iodine-125 and fluorine-18.
abstract: Methods for labeling the glutamate channel blocking agent MK-801 with iodine-125 (125I) and fluorine-18 (18F) are described. Radioiodine was incorporated in the 1- or 3-positions of the aromatic ring of (+/-)MK-801 by solid-state halogen exchange techniques. Attachment of the [18F]fluoromethyl group to the bridgehead methyl position was achieved by reaction of [18F]fluoride with the triflamide alcohol 8 or the novel cyclic sulfamate 9 recently reported by Merck chemists. Radiochemical yields of (+/-) 13-[18F]-fluoromethyl-MK-801 were greater than 72%, EOB; radiochemical purity greater than 99%. In competitive binding studies using rat brain homogenates, (+/-)3-bromo-MK-801 showed greater affinity than (+/-)MK-801 for the glutamate-linked channel. The experimental log P (2.1 +/- 0.1) of MK-801 is optimal for transit of the blood-brain barrier. These preliminary findings support further testing of 3-[123 I]iodo-MK-801 and (+/-)13-[18F]fluoromethyl-MK-801 as possible agents for in vivo mapping of the glutamate receptor complex.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109.
authors.forename: D M
authors.initials: DM
authors.lastname: Wieland
authors.forename: M R
authors.initials: MR
authors.lastname: Kilbourn
authors.forename: D J
authors.initials: DJ
authors.lastname: Yang
authors.forename: E
authors.initials: E
authors.lastname: Laborde
authors.forename: D L
authors.initials: DL
authors.lastname: Gildersleeve
authors.forename: M E
authors.initials: ME
authors.lastname: Van Dort
authors.forename: J L
authors.initials: JL
authors.lastname: Pirat
authors.forename: B J
authors.initials: BJ
authors.lastname: Ciliax
authors.forename: A B
authors.initials: AB
authors.lastname: Young
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000378:metabolism*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D003986:Dibenzocycloheptenes / Q000138:chemical synthesis / Q000378:metabolism*; D016291:Dizocilpine Maleate; D005462:Fluorine Radioisotopes; D007457:Iodine Radioisotopes; D008297:Male; D016202:N-Methylaspartate; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000378:metabolism*
chemical_list: D000927:Anticonvulsants; D003986:Dibenzocycloheptenes; D005462:Fluorine Radioisotopes; D007457:Iodine Radioisotopes; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate