title: Time-course of serotonin transporter occupancy by single dose of three SSRIs in human brain: A positron emission tomography study with [(11)C]DASB.
abstract: Sixteen healthy volunteers were enrolled and divided into four groups according to the single administration of 10mg or 20mg escitalopram, 50mg sertraline, or 20mg paroxetine. Four positron emission tomography scans with [(11)C]DASB were performed on each subject, the first prior to taking the drug, followed by the others at 4, 24, and 48h after. Serotonin transporter occupancies of the drugs at each time point were calculated. All drugs showed maximum occupancy at 4h after dosing and then decreasing occupancies with time. Escitalopram and sertraline showed high occupancies of 69.1-77.9% at 4h, remaining at 52.8-57.8% after 48h. On the other hand, paroxetine showed relatively low occupancy of 44.6%, then decreasing to 10.3% at 48h. Escitalopram (both 10mg and 20mg) and sertraline (50mg) showed high and sustained occupancy. Paroxetine (20mg) showed relatively low and rapidly decreasing occupancy, possibly due to the low plasma concentration by single dosing schedule. Applying the reported concentration of multiple dosing, 20mg paroxetine will induce over 80% occupancy. The present study suggested that these drugs and doses would be sufficient for the treatment of depression.
authors.affiliation: Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Arakawa
authors.affiliation: Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan.
authors.forename: Amane
authors.initials: A
authors.lastname: Tateno
authors.affiliation: Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan.
authors.forename: WooChan
authors.initials: W
authors.lastname: Kim
authors.affiliation: Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sakayori
authors.affiliation: Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Ogawa
authors.affiliation: Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan. Electronic address: okubo-y@nms.ac.jp.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Okubo
mesh_terms: D000328:Adult; D001596:Benzylamines / Q000378:metabolism / Q000494:pharmacology; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000378:metabolism* / Q000494:pharmacology; D015283:Citalopram / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D017374:Paroxetine / Q000378:metabolism / Q000494:pharmacology; D049268:Positron-Emission Tomography / Q000379:methods*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D020280:Sertraline / Q000378:metabolism / Q000494:pharmacology; D055815:Young Adult
chemical_list: D001596:Benzylamines; D002250:Carbon Radioisotopes; D015283:Citalopram; D017374:Paroxetine; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; C420885:N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine
keywords: Occupancy; Positron emission tomography; Selective serotonin reuptake inhibitor; Time-course; [(11)C]DASB