Synthesis and characterization of a radiolabelled derivative of the phencyclidine/N-methyl-D-aspartate receptor ligand (+) MK-801 with high specific radioactivity.
A [3H]-labelled derivative of the drug (+)MK-801 with a high specific radioactivity was synthesized by first preparing a tribromo derivative of (+)MK-801 followed by catalytic reduction in the presence of [3H]-gas and subsequent purification of the radioactive product by reversed-phase high performance liquid chromatography (RP-HPLC). This resulted in pure (+) [3H]MK-801 with a specific radioactivity of 97 Ci/mmol. The (+) [3H]MK-801 was shown to interact with high affinity and selectivity with the phencyclidine (PCP) receptor in guinea pig brain membrane suspensions. The PCP receptor is associated with a cation channel that is chemically gated by glutamate and N-methyl-D-aspartate (NMDA). Drugs that interact with the PCP receptor block this channel. The (+) [3H]MK-801 described here will be useful to investigate the biochemistry of PCP/NMDA receptors in experiments where a high specific radioactivity is essential.
Keana
J F
JF
Department of Chemistry, University of Oregon, Eugene 97403.
Scherz
M W
MW
Quarum
M
M
Sonders
M S
MS
Weber
E
E
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D003986:Dibenzocycloheptenes / Q000138:chemical synthesis / Q000378:metabolism*; D016291:Dizocilpine Maleate; D006168:Guinea Pigs; D007202:Indicators and Reagents; D007553:Isotope Labeling / Q000379:methods; D007700:Kinetics; D008566:Membranes / Q000378:metabolism; D010622:Phencyclidine / Q000378:metabolism*; D011869:Radioligand Assay; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D017478:Receptors, Phencyclidine; D014316:Tritium
D003986:Dibenzocycloheptenes; D007202:Indicators and Reagents; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D014316:Tritium; D016291:Dizocilpine Maleate; D010622:Phencyclidine