Synthesis, radiolabeling and preliminary biological evaluation of radiolabeled 5-methyl-6-nitroquipazine, a potential radioligand for the serotonin transporter.
5-Methyl-6-nitroquipazine, a novel analogue of the potent and selective serotonin transporter inhibitor 6-nitroquipazine was synthesized and radiolabeled with tritium and the positron emitter carbon-11. [3H]5-methyl-6-nitroquipazine was found to have a K(d)=51+/-7 pM. The high affinity and the facile labeling of [11C]5-methyl-6-nitroquipazine makes it a promising radioligand for visualization of the serotonin transporter with positron emission tomography.
Sandell
Johan
J
Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-171 76 Stockholm, Sweden. johan.sandell@pet.uu.se
Yu
Meixiang
M
Emond
Patrick
P
Garreau
Lucette
L
Chalon
Sylvie
S
Någren
Kjell
K
Guilloteau
Denis
D
Halldin
Christer
C
D000818:Animals; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D008024:Ligands; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017397:Prefrontal Cortex / Q000378:metabolism; D011814:Quipazine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins; D013329:Structure-Activity Relationship; D014316:Tritium
C471420:5-methyl-6-nitroquipazine; D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D019275:Radiopharmaceuticals; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D014316:Tritium; D011814:Quipazine