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.
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.
Prabhakaran
Jaya
J
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, New York, NY 10032, USA.
Parsey
Ramin V
RV
Majo
Vattoly J
VJ
Hsiung
Shu-Chi
SC
Milak
Matthew S
MS
Tamir
Hadassah
H
Simpson
Norman R
NR
Van Heertum
Ronald L
RL
Mann
J John
JJ
Dileep Kumar
J S
JS
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
D004224:Diterpenes; D008024:Ligands; D058825:Serotonin 5-HT1 Receptor Agonists; D014227:Triazines; C510707:celahypodiol 1