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Characterization of in vivo pharmacological properties and sensitivity to endogenous serotonin of [ 11 C] P943: A positron emission tomography study in Papio anubis
Author(s) -
Ridler Khanum,
Plisson Christophe,
Rabiner Eugenii A.,
Gunn Roger N.,
Easwaramoorthy Balu,
AbiDargham Anissa,
Laruelle Marc,
Slifstein Mark
Publication year - 2011
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20946
Subject(s) - positron emission tomography , in vivo , endogeny , serotonin , chemistry , neuroscience , psychology , biology , biochemistry , receptor , microbiology and biotechnology
[ 11 C] P943 is a recently developed PET radiotracer for serotonin 5‐HT 1B receptors. We characterized a number of its in vivo pharmacokinetic properties, including the evaluation of its two stereo‐isomers, saturability of specific binding, selectivity for 5‐HT 1B and 5‐HT 1D receptors, and vulnerability to pharmacologically induced increases in endogenous 5‐HT levels. Six isoflurane‐anesthetized baboons were scanned with [ 11 C] P943 at baseline, and following various pharmacological manipulations. The interventions included the administration of pharmacological doses of P943, SB‐616234‐S (a 5‐HT 1B selective antagonist), SB‐714786 (a 5‐HT 1D selective antagonist), as well as the administration of 5‐HT releasing agents (fenfluramine, amphetamine) and 5‐HT reuptake inhibitor (citalopram). [ 11 C] P943 was observed to bind saturably and specifically to 5‐HT 1B receptors and to be sensitive to all three challenges known to alter 5‐HT levels in the proximity of receptors. [ 11 C] P943 shows promise as a tracer to image serotonin function in healthy subjects as well as subjects with psychiatric or neurologic conditions. Synapse, 2011. © 2011 Wiley‐Liss, Inc.