title: Characterization of in vivo pharmacological properties and sensitivity to endogenous serotonin of [11C] P943: a positron emission tomography study in Papio anubis.
abstract: [11 C] P943 is a recently developed PET radiotracer for serotonin 5-HT1B 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-HT1B and 5-HT1D 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-HT1B selective antagonist), SB-714786 (a 5-HT1D 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-HT1B 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.
authors.affiliation: GlaxoSmithKline, Clinical Imaging Centre, London, UK.
authors.forename: Khanum
authors.initials: K
authors.lastname: Ridler
authors.forename: Christophe
authors.initials: C
authors.lastname: Plisson
authors.forename: Eugenii A
authors.initials: EA
authors.lastname: Rabiner
authors.forename: Roger N
authors.initials: RN
authors.lastname: Gunn
authors.forename: Balu
authors.initials: B
authors.lastname: Easwaramoorthy
authors.forename: Anissa
authors.initials: A
authors.lastname: Abi-Dargham
authors.forename: Marc
authors.initials: M
authors.lastname: Laruelle
authors.forename: Mark
authors.initials: M
authors.lastname: Slifstein
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D048530:Papio anubis; D010879:Piperazines / Q000378:metabolism* / Q000494:pharmacology*; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding / Q000502:physiology; D011760:Pyrrolidinones / Q000378:metabolism* / Q000494:pharmacology*; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism* / Q000502:physiology
chemical_list: C546827:1-(4-(2-methoxyisopropyl)phenyl)-3-(2-(4-methylpiperazin-1-yl)benzyl)pyrrolidin-2-one; D002250:Carbon Radioisotopes; D010879:Piperazines; D011760:Pyrrolidinones; D044302:Receptor, Serotonin, 5-HT1B; D012701:Serotonin