title: Synthesis, in vitro and in vivo evaluation of [O-methyl-11C] 2-{4-[4-(3-methoxyphenyl)piperazin-1-yl]-butyl}-4-methyl-2H-[1,2,4]-triazine-3,5-dione: a novel agonist 5-HT1A receptor PET ligand.
abstract: Synthesis and in vivo evaluation of 2-{4-[4-(3-methoxyphenyl)piperazin-1-yl]-butyl}-4-methyl-2H-[1,2,4]triazine-3,5-dione (5 or MMT), a high affinity and selective serotonin 5-HT1AR agonist PET tracer, are described. GTPgammaS assay shows that MMT is an agonist with an EC50 comparable to 5-HT. Radiolabeling of 5 was achieved in 30% yield (EOS) from desmethyl-MMT (4) with >99% chemical and radiochemical purities and a specific activity >1000 Ci/mmol. PET studies in baboon show that [11C]5 penetrates the blood-brain barrier but, because of low specific binding and fast clearance of radioactivity it is not a suitable PET tracer for the in vivo quantification of 5-HT1AR.
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, New York, NY 10032, USA.
authors.forename: Jaya
authors.initials: J
authors.lastname: Prabhakaran
authors.forename: Ramin V
authors.initials: RV
authors.lastname: Parsey
authors.forename: Vattoly J
authors.initials: VJ
authors.lastname: Majo
authors.forename: Shu-Chi
authors.initials: SC
authors.lastname: Hsiung
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Milak
authors.forename: Hadassah
authors.initials: H
authors.lastname: Tamir
authors.forename: Norman R
authors.initials: NR
authors.lastname: Simpson
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Van Heertum
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
authors.forename: J S
authors.initials: JS
authors.lastname: Dileep Kumar
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging; D016466:CHO Cells; D006224:Cricetinae; D004224:Diterpenes / Q000302:isolation & purification* / Q000494:pharmacology; D008024:Ligands; D008279:Magnetic Resonance Imaging; D010215:Papio; D049268:Positron-Emission Tomography; D011869:Radioligand Assay / Q000379:methods*; D058825:Serotonin 5-HT1 Receptor Agonists; D014227:Triazines / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D004224:Diterpenes; D008024:Ligands; D058825:Serotonin 5-HT1 Receptor Agonists; D014227:Triazines; C510707:celahypodiol 1