Abstract
Introduction
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.
Materials and methods
In the present study, we used positron emission tomography (PET) and autoradiography to study effects of (R)- and (S)-[11C]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)-[11C]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 [3H]clonidine binding at α2-adrenoceptors.
Conclusion
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)-[11C]mirtazapine in the living human brain.
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Acknowledgments
We thank Organon, Oss, Holland for generous supplies of unlabeled mirtazapine enantiomers, Alexandra Tylec of Karolinska Institutet for help with autoradiographic experiments, and the Danish Medical Research Council for financial support. The authors have no conflicts of interest related to these research findings.
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Smith, D.F., Hansen, S.B., Jakobsen, S. et al. Neuroimaging of mirtazapine enantiomers in humans. Psychopharmacology 200, 273–279 (2008). https://doi.org/10.1007/s00213-008-1208-6
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DOI: https://doi.org/10.1007/s00213-008-1208-6