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Receptor occupancy of mirtazapine determined by PET in healthy volunteers

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Abstract

Rationale

Molecular tools are needed for assessing anti-depressant actions by positron emission tomography (PET) in the living human brain.

Objectives

This study determined whether [11C]mirtazapine is an appropriate molecular tool for use with PET to estimate the magnitude of neuroreceptor occupancy produced by daily intake of mirtazapine.

Methods

This study used a randomised, double-blind, placebo-controlled, parallel-group, within-subject design. Eighteen healthy volunteers were PET-scanned twice with [11C]mirtazapine; once under baseline condition and again after receiving either placebo or mirtazapine (7.5 or 15 mg) for 5 days. We determined kinetic parameters of [11C]mirtazapine in brain regions by the simplified reference region method and used binding potential values to calculate receptor occupancy produced by mirtazapine.

Results

Serum concentrations of mirtazapine ranged from 33 to 56 nmol/l after five daily doses of 7.5 mg mirtazapine and were between 41 and 74 nmol/l after 15 mg mirtazapine. Placebo treatment failed to alter the binding potential of [11C]mirtazapine from baseline values, whereas daily intake of mirtazapine markedly decreased the binding potential in cortex, amygdala and hippocampus. Receptor occupancy ranged from 74 to 96% in high-binding regions of the brain after five daily doses of 7.5 mg or 15 mg mirtazapine, whereas 17–48% occupancy occurred in low-binding regions.

Conclusions

[11C]Mirtazapine together with PET can determine the degree of receptor occupancy produced by daily doses of mirtazapine in regions of the living human brain.

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Acknowledgements

Funded by the Danish Medical Research Council, the A.P. Møller Foundation for the Advancement of Medical Science, and the Max and Inger Woerzner Foundation.

Dr. Donald F. Smith reports no competing interests. The authors thank Dr. Marie M. Nielsen, the bioanalysts at the PET Center and Center for Psychiatric Research, and the technicians at the PET Center for their skilful assistance.

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Authors and Affiliations

  1. Center for Psychiatric Research, Psychiatric Hospital of Aarhus University, 8240, Risskov, Denmark

    Donald F. Smith, Bo S. Stork, Gregers Wegener & Raben Rosenberg

  2. PET Center, Aarhus University Hospital, 8000, Aarhus C, Denmark

    Steen Jakobsen, Dirk Bender, Hélène Audrain, Svend B. Jensen, Søren B. Hansen & Anders Rodell

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  1. Donald F. Smith
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  2. Bo S. Stork
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Correspondence to Donald F. Smith.

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Smith, D.F., Stork, B.S., Wegener, G. et al. Receptor occupancy of mirtazapine determined by PET in healthy volunteers. Psychopharmacology 195, 131–138 (2007). https://doi.org/10.1007/s00213-007-0877-x

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  • DOI: https://doi.org/10.1007/s00213-007-0877-x

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