In vivo study of NMDA-sensitive glutamate receptor by fluorothienylcyclohexylpiperidine [correction of fluorothienylcycloexylpiperidine], a possible ligand for positron emission tomography.
As a preliminary to positron emission tomography (PET) studies of excitatory amino acid neurotransmission, N-methyl-D-aspartate (NMDA)-sensitive glutamate receptors of mice and rats were labelled in vivo with [3H]fluorothienylcyclohexylpiperidine [corrected] (FTCP), which binds to the phencyclidine site of the NMDA receptor. After intravenous injection, the half-life of clearance of authentic FTCP from blood was 4.2 min in mice, 12 min in rats and 45 min in a rhesus monkey. In rodent brain, the specific binding of [3H]FTCP, 10 min after intravenous injection, was 10-20% of the total binding and no regional differences were observed. However, if animals were treated with NMDA intraperitoneally (0.68 mmol/kg), 10 min before injection of [3H]FTCP, a three- to five-fold increase in specific binding was observed in hippocampus, cerebral cortex and striatum but not in cerebellum. Thus, specific binding of [3H]FTCP in vivo revealed the physiological status of the NMDA receptor; in fact, preliminary PET studies with [18F]FTCP in monkeys indicated increased binding after activation of NMDA receptors. These data suggest that PET with [18F]FTCP can be a tool to evaluate physiological or pathological modifications of the function of NMDA receptors.
Neuroimaging Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
C
C
Ferrarese
A
A
Guidotti
E
E
Costa
R S
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Miletich
K C
KC
Rice
B R
BR
de Costa
M J
MJ
Fulham
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G
Di Chiro
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D005998:Glycine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology*; D010880:Piperidines / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism*; D014055:Tomography, Emission-Computed / Q000379:methods*
D005971:Glutamates; D010880:Piperidines; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D018698:Glutamic Acid; D016202:N-Methylaspartate; C072704:4-fluoro-1-(1-(2-thienyl)cyclohexyl)piperidine; D005998:Glycine