title: Fenfluramine-induced serotonin release decreases [11C]AZ10419369 binding to 5-HT1B-receptors in the primate brain.
abstract: The need for positron emission tomography (PET)-radioligands that are sensitive to changes in endogenous serotonin (5-HT) levels in brain is recognized in experimental and clinical psychiatric research. We recently developed the novel PET radioligand [(11)C]AZ10419369 that is highly selective for the 5-HT(1B) receptor. In this PET-study in three cynomolgus monkeys, we examined the sensitivity of [(11)C]AZ10419369 to altered endogenous 5-HT levels. Fenfluramine-induced 5-HT release decreased radioligand binding in a dose-dependent fashion with a regional average of 27% after 1 mg/kg and 50% after 5 mg/kg. This preliminary study supports that [(11)C]AZ10419369 is sensitive to endogenous 5-HT levels in vivo and may serve as a tool to examine the pathophysiology and treatment of major psychiatric disorders.
authors.affiliation: Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Stockholm, Sweden. Sjoerd.Finnema@ki.se
authors.forename: S J
authors.initials: SJ
authors.lastname: Finnema
authors.forename: A
authors.initials: A
authors.lastname: Varrone
authors.forename: T J
authors.initials: TJ
authors.lastname: Hwang
authors.forename: B
authors.initials: B
authors.lastname: Gulyás
authors.forename: M E
authors.initials: ME
authors.lastname: Pierson
authors.forename: C
authors.initials: C
authors.lastname: Halldin
authors.forename: L
authors.initials: L
authors.lastname: Farde
mesh_terms: D000818:Animals; D001578:Benzopyrans; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes; D004305:Dose-Response Relationship, Drug; D005260:Female; D005277:Fenfluramine / Q000008:administration & dosage / Q000494:pharmacology*; D008252:Macaca fascicularis; D009025:Morpholines; D010879:Piperazines; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
chemical_list: C530629:5-methyl-8-(4-methyl-piperazin-1-yl)-4-oxo-4H-chromene-2-carboxylic acid (4-morpholin-4-yl-phenyl)amide; D001578:Benzopyrans; D002250:Carbon Radioisotopes; D009025:Morpholines; D010879:Piperazines; D019275:Radiopharmaceuticals; D044302:Receptor, Serotonin, 5-HT1B; D018490:Serotonin Agents; D005277:Fenfluramine; D012701:Serotonin