PMID- 27128179
OWN - NLM
STAT- MEDLINE
DCOM- 20170207
LR  - 20170207
IS  - 1768-3254 (Electronic)
IS  - 0223-5234 (Linking)
VI  - 118
DP  - 2016 Aug 8
TI  - Synthesis, radiolabeling and evaluation of novel amine guanidine derivatives as 
      potential positron emission tomography tracers for the ion channel of the 
      N-methyl-d-aspartate receptor.
PG  - 143-60
LID - S0223-5234(16)30307-5 [pii]
LID - 10.1016/j.ejmech.2016.04.022 [doi]
AB  - The N-Methyl-d-Aspartate receptor (NMDAR) is involved in many neurological and 
      psychiatric disorders including Alzheimer's disease and schizophrenia. The aim of 
      this study was to develop a positron emission tomography (PET) ligand to assess 
      the bio-availability of the NMDAR ion channel in vivo. A series of 
      tri-N-substituted diarylguanidines was synthesized and their in vitro binding 
      affinities for the NMDAR ion channel assessed in rat forebrain membrane 
      fractions. Compounds 21, 23 and 26 were radiolabeled with either carbon-11 or 
      fluorine-18 and ex vivo biodistribution and metabolite studies were performed in 
      Wistar rats. Biodistribution studies showed high uptake especially in prefrontal 
      cortex and lowest uptake in cerebellum. Pre-treatment with MK-801, however, did 
      not decrease uptake of the radiolabeled ligands. In addition, all three ligands 
      showed fast metabolism.
CI  - Copyright (c) 2016 Elsevier Masson SAS. All rights reserved.
FAU - Klein, Pieter J
AU  - Klein PJ
AD  - Department of Radiology & Nuclear Medicine, Neuroscience Campus Amsterdam, VU 
      University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. 
      Electronic address: pj.klein@vumc.nl.
FAU - Chomet, Marion
AU  - Chomet M
AD  - Department of Radiology & Nuclear Medicine, Neuroscience Campus Amsterdam, VU 
      University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
FAU - Metaxas, Athanasios
AU  - Metaxas A
AD  - Department of Radiology & Nuclear Medicine, Neuroscience Campus Amsterdam, VU 
      University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
FAU - Christiaans, Johannes A M
AU  - Christiaans JA
AD  - Department of Radiology & Nuclear Medicine, Neuroscience Campus Amsterdam, VU 
      University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
FAU - Kooijman, Esther
AU  - Kooijman E
AD  - Department of Radiology & Nuclear Medicine, Neuroscience Campus Amsterdam, VU 
      University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
FAU - Schuit, Robert C
AU  - Schuit RC
AD  - Department of Radiology & Nuclear Medicine, Neuroscience Campus Amsterdam, VU 
      University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
FAU - Lammertsma, Adriaan A
AU  - Lammertsma AA
AD  - Department of Radiology & Nuclear Medicine, Neuroscience Campus Amsterdam, VU 
      University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
FAU - van Berckel, Bart N M
AU  - van Berckel BN
AD  - Department of Radiology & Nuclear Medicine, Neuroscience Campus Amsterdam, VU 
      University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
FAU - Windhorst, Albert D
AU  - Windhorst AD
AD  - Department of Radiology & Nuclear Medicine, Neuroscience Campus Amsterdam, VU 
      University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
LA  - eng
PT  - Journal Article
DEP - 20160419
PL  - France
TA  - Eur J Med Chem
JT  - European journal of medicinal chemistry
JID - 0420510
RN  - 0 (Amines)
RN  - 0 (Radioactive Tracers)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - JU58VJ6Y3B (Guanidine)
SB  - IM
MH  - Amines/*chemistry
MH  - Animals
MH  - Chemistry Techniques, Synthetic
MH  - Guanidine/*chemical synthesis/*chemistry/metabolism/pharmacokinetics
MH  - Hydrophobic and Hydrophilic Interactions
MH  - Isotope Labeling
MH  - Male
MH  - Positron-Emission Tomography/*methods
MH  - Radioactive Tracers
MH  - Radiochemistry
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Tissue Distribution
OTO - NOTNLM
OT  - NMDA
OT  - Non-competitive antagonists
OT  - PET
OT  - Radiolabeling
OT  - SAR
EDAT- 2016/04/30 06:00
MHDA- 2017/02/09 06:00
CRDT- 2016/04/30 06:00
PHST- 2015/04/29 00:00 [received]
PHST- 2016/04/06 00:00 [revised]
PHST- 2016/04/07 00:00 [accepted]
PHST- 2016/04/30 06:00 [entrez]
PHST- 2016/04/30 06:00 [pubmed]
PHST- 2017/02/09 06:00 [medline]
AID - S0223-5234(16)30307-5 [pii]
AID - 10.1016/j.ejmech.2016.04.022 [doi]
PST - ppublish
SO  - Eur J Med Chem. 2016 Aug 8;118:143-60. doi: 10.1016/j.ejmech.2016.04.022. Epub 
      2016 Apr 19.