Neuroimaging of mirtazapine enantiomers in humans.
BACKGROUND
Mirtazapine is a racemic antidepressant with a multireceptor profile. Previous studies have shown that the enantiomers of mirtazapine have different pharmacologic effects in the brain of laboratory animals.


METHODS
In the present study, we used positron emission tomography (PET) and autoradiography to study effects of (R)- and (S)-[(11)C]mirtazapine in the human brain. Detailed brain imaging by PET using three methods of kinetic data analysis showed no reliable differences between regional binding potentials of (R)- and (S)-[(11)C]mirtazapine in healthy subjects.


RESULTS
Autoradiographic studies carried out in whole hemispheres of human brain tissue showed, however, that (R)- and (S)-mirtazapine differ markedly as inhibitors of [(3)H]clonidine binding at alpha(2)-adrenoceptors.


CONCLUSIONS
The multireceptor binding profiles of mirtazapine enantiomers, along with individual differences between subjects, may preclude PET neuroimaging from demonstrating reliable differences between the regional distribution and binding of (R)- and (S)-[(11)C]mirtazapine in the living human brain.
Center for Psychiatric Research, Psychiatric Hospital of Aarhus University, 8240, Risskov, Denmark. dfsmith@inet.uni2.dk
Donald F
DF
Smith
Søren B
SB
Hansen
Steen
S
Jakobsen
Dirk
D
Bender
Hélène
H
Audrain
Mahmoud
M
Ashkanian
Bo S
BS
Stork
Luciano
L
Minuzzi
Håkan
H
Hall
Raben
R
Rosenberg
D000317:Adrenergic alpha-Antagonists / Q000493:pharmacokinetics; D000929:Antidepressive Agents, Tricyclic / Q000493:pharmacokinetics*; D001345:Autoradiography / Q000379:methods; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000000981:diagnostic imaging*; D002250:Carbon Radioisotopes; D003000:Clonidine / Q000493:pharmacokinetics; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008875:Middle Aged; D000078785:Mirtazapine; D049268:Positron-Emission Tomography / Q000379:methods*; D011869:Radioligand Assay / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013237:Stereoisomerism; D014018:Tissue Distribution; D055815:Young Adult
D000317:Adrenergic alpha-Antagonists; D000929:Antidepressive Agents, Tricyclic; D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D008803:Mianserin; D000078785:Mirtazapine; D003000:Clonidine