Influence of synaptic serotonin level on [18F]altanserin binding to 5HT2 receptors in man.
The feasibility of in vivo serotonin 5HT(2) receptor binding measurement using [18F]altanserin as a radioligand has been well established. In this study, the postsynaptic receptor binding potential of this ligand was examined as a possible indicator of synaptic serotonin content after pharmacological challenge. Studies were performed in 11 subjects with a history of recurrent major depression. Six of them received serotonergic antidepressive treatment at the time of the experiment, the other five patients were untreated. Two PET measurements were carried out in each subject within 2 or 3 days. Before one of the measurements, 25 mg of the serotonin re-uptake inhibitor clomipramine were given intravenously, the other measurement was done without pharmacological challenge. The data were analyzed using non-linear least-square regression and Logan's graphical method. In the whole group of subjects, binding potential and distribution volume of altanserin decreased following clomipramine challenge. The decrease was between 14 (P=0.03) and 23% (P=0.004). This effect was mainly seen in subjects not on antidepressive medication. Clomipramine challenge probably increased the synaptic serotonin level, which competed with altanserin leading to the lowered binding potential. The paradigm might, thus, be useful to estimate serotonin release in vivo. Pretreatment with serotonergic antidepressants reduces the effect of clomipramine.
Larisch
Rolf
R
Department of Nuclear Medicine, Heinrich-Heine-University of Düsseldorf, Moorenstr. 5, Dusseldorf, Germany. rolf.larisch@uni-duesseldorf.de
Klimke
Ansgar
A
Hamacher
Kurt
K
Henning
Uwe
U
Estalji
Sorour
S
Hohlfeld
Thomas
T
Vosberg
Henning
H
Tosch
Marco
M
Gaebel
Wolfgang
W
Coenen
Heinz H
HH
Müller-Gärtner
Hans Wilhelm
HW
D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D002997:Clomipramine / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology*; D004347:Drug Interactions; D005240:Feasibility Studies; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D006801:Humans; D007650:Ketanserin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011985:Receptors, Serotonin / Q000378:metabolism*; D012008:Recurrence; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000493:pharmacokinetics; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D009435:Synaptic Transmission / Q000502:physiology; D014055:Tomography, Emission-Computed
D000929:Antidepressive Agents, Tricyclic; D002997:Clomipramine; D005462:Fluorine Radioisotopes; D007650:Ketanserin; D011985:Receptors, Serotonin; D012701:Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C071983:altanserin