Comparison of high and low affinity serotonin 1A receptors by PET in vivo in nonhuman primates.
Serotonin (5-HT) 1A receptors exist in high and low affinity states. Agonist ligands bind preferentially to the high affinity state receptors, providing a more functionally relevant measure than antagonist binding. We now report comparison of 5-HT(1A) binding in vivo using both [¹¹C]CUMI-101 (agonist) and [¹¹C]WAY100635 (antagonist) in nonhuman primates. PET studies show that both tracers bind to known 5-HT(1A) receptor (5-HT(1A)R)-rich regions of baboon brain. The binding (BP(F)) of [¹¹C]CUMI-101 was lower on an average of 55% across the regions of interest (ROIs) compared to [¹¹C]WAY100635. This ratio is consistent with the in vitro binding data of agonist and antagonist 5-HT(1A)R ligands previously reported.
Division of Molecular Imaging and Neuropathology, Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. dk2038@columbia.edu
J S Dileep
JS
Kumar
Matthew S
MS
Milak
Vattoly J
VJ
Majo
Jaya
J
Prabhakaran
Pratap
P
Mali
Lyudmila
L
Savenkova
J John
JJ
Mann
Ramin V
RV
Parsey
D000818:Animals; D001921:Brain / Q000378:metabolism*; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D006801:Humans; D007700:Kinetics; D008024:Ligands; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010215:Papio; D010879:Piperazines / Q000378:metabolism; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000378:metabolism*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000378:metabolism*; D014227:Triazines / Q000378:metabolism
C529131:2-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5-(2H,4H)-dione; D002250:Carbon Radioisotopes; D008024:Ligands; D009419:Nerve Tissue Proteins; D010879:Piperazines; D011725:Pyridines; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D014227:Triazines; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide