Ketamine displaces the novel NMDA receptor SPET probe [(123)I]CNS-1261 in humans in vivo.
[(123)I]CNS-1261 [N-(1-naphthyl)-N'-(3-iodophenyl)-N-methylguanidine] is a high-affinity SPET ligand with selectivity for the intra-channel PCP/ketamine/MK-801 site of the N-methyl-d-aspartate (NMDA) receptor. This study evaluated the effects of ketamine (a specific competitor for the intra-channel PCP/ketamine/MK-801 site) on [(123)I]CNS-1261 binding to NMDA receptors in vivo. Ten healthy volunteers underwent 2 bolus-plus-infusion [(123)I]CNS-1261 scans, one during placebo and the other during a ketamine challenge. Ketamine administration led to a significant decrease in [(123)I]CNS-1261 V(T) in most of the brain regions examined (P<.05). [(123)I]CNS-1261 appears to be a specific ligand in vivo for the intra-channel PCP/ketamine/MK-801 NMDA binding site.
Institute of Psychiatry, King's College London, De Crespigny Park London, SE5 8AF UK. j.stone@iop.kcl.ac.uk
James M
JM
Stone
Kjell
K
Erlandsson
Erik
E
Arstad
Rodrigo A
RA
Bressan
Lisa
L
Squassante
Vincenza
V
Teneggi
Peter J
PJ
Ell
Lyn S
LS
Pilowsky
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D018592:Cross-Over Studies; D006146:Guanidines / Q000493:pharmacokinetics*; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D007649:Ketamine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D015336:Molecular Probe Techniques; D015990:Placebo Effect; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D016037:Single-Blind Method; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
C417904:CNS 1261; D006146:Guanidines; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine