Linked Life Data

9639292

Source:http://linkedlifedata.com/resource/pubmed/id/9639292

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1998-9-17
pubmed:abstractText
The effect of the fluorinated memantine derivative and NMDA receptor antagonist, 1-amino-3-fluoromethyl-5-methyl-adamantane (19F-MEM), at the NMDA receptor ion channel was studied by patch clamp recording. The results showed that 19F-MEM is a moderate NMDA receptor channel blocker. A procedure for the routine preparation of the 18F-labelled analog 18F-MEM has been developed using a two-step reaction sequence. This involves the no-carrier-added nucleophilic radiofluorination of 1-[N-(tert-butyloxy)carbamoyl]-3-(toluenesulfonyloxy)methyl- 5-methyl-adamantane and the subsequent cleavage of the BOC-protecting group using aqueous HCI. The 18F-MEM was obtained in 22 +/- 7% radiochemical yield (decay-corrected to EOB) in a total synthesis time including HPLC purification of 90 min. A biodistribution study after i.v. injection of 18F-MEM in mice showed a fast clearance of radioactivity from blood and relatively high initial uptake in the kidney and in the lung, which gradually decreased with time. The brain uptake was high (up to 3.6% ID/g, 60 min postinjection) with increasing brain-blood ratios: 2.40, 5.10, 6.33, and 9.27 at 5, 30, 60, and 120 min, respectively. The regional accumulation of the radioactivity in the mouse brain was consistent with the known distribution of the PCP recognition site. Preliminary PET evaluation of the radiotracer in a rhesus monkey demonstrated good uptake and prolonged retention in the brain, with a plateau from 35 min onwards p.i. in the NMDA receptor-rich regions (frontal cortex, striata, and temporal cortex). Delineation of the hippocampus, a region known to contain a high density of NMDA receptors, was not possible owing to the resolution of the PET tomograph. The regional brain uptake of 18F-MEM was changed by memantine and by a pharmacological dose of (+)-MK-801, indicating competition for the same binding sites. In a preliminary experiment, haloperidol, a dopamine D2 and sigma receptor antagonist, decreased the binding of 18F-MEM from the brain regions examined, suggesting that binding was also occurring to the sigma recognition sites.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0969-8051
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
323-30
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed-meshheading:9639292-Animals, pubmed-meshheading:9639292-Binding, Competitive, pubmed-meshheading:9639292-Blood-Brain Barrier, pubmed-meshheading:9639292-Brain, pubmed-meshheading:9639292-Dizocilpine Maleate, pubmed-meshheading:9639292-Electrophysiology, pubmed-meshheading:9639292-Excitatory Amino Acid Antagonists, pubmed-meshheading:9639292-Female, pubmed-meshheading:9639292-Fluorine Radioisotopes, pubmed-meshheading:9639292-Macaca mulatta, pubmed-meshheading:9639292-Memantine, pubmed-meshheading:9639292-Mice, pubmed-meshheading:9639292-Mice, Inbred ICR, pubmed-meshheading:9639292-Patch-Clamp Techniques, pubmed-meshheading:9639292-Radioligand Assay, pubmed-meshheading:9639292-Radiopharmaceuticals, pubmed-meshheading:9639292-Receptors, N-Methyl-D-Aspartate, pubmed-meshheading:9639292-Tissue Distribution, pubmed-meshheading:9639292-Tomography, Emission-Computed
pubmed:year
1998
pubmed:articleTitle
Electrophysiological study, biodistribution in mice, and preliminary PET evaluation in a rhesus monkey of 1-amino-3-[18F]fluoromethyl-5-methyl-adamantane (18F-MEM): a potential radioligand for mapping the NMDA-receptor complex.
pubmed:affiliation
Centre for Radiopharmacy, Paul Scherrer Institute, Villigen, Switzerland.
pubmed:publicationType
Journal Article