Papers

Oct 16, 2012

Occupancy of serotonin and norepinephrine transporter by milnacipran in patients with major depressive disorder: a positron emission tomography study with [(11)C]DASB and (S,S)-[(18)F]FMeNER-D(2).

The international journal of neuropsychopharmacology
  • Hitoshi SHIMADA

Volume
16
Number
5
First page
937
Last page
43
Language
English
Publishing type
Research paper (scientific journal)
DOI
10.1017/s1461145712001009, 10.1017/S1461145712001009

Antidepressants used for treatment of depression exert their efficacy by blocking reuptake at serotonin transporters (5-HTT) and/or norepinephrine transporters (NET). Recent studies suggest that serotonin and norepinephrine reuptake inhibitors that block both 5-HTT and NET have better tolerability than tricyclic antidepressants and may have higher efficacy compared to selective serotonin reuptake inhibitors. Previous positron emission tomography (PET) studies have reported >80% 5-HTT occupancy with clinical doses of antidepressants, but there has been no report of NET occupancy in patients treated with antidepressants. In the present study, we investigated both 5-HTT and NET occupancies by PET using radioligands [(11)C]DASB and (S,S)-[(18)F]FMeNER-D(2), in six patients, each with major depressive disorder (MDD), using various doses of milnacipran. Our data show that mean 5-HTT occupancy in the thalamus was 33.0% at 50 mg, 38.6% at 100 mg, 60.0% at 150 mg and 61.5% at 200 mg. Mean NET occupancy in the thalamus was 25.3% at 25 mg, 40.0% at 100 mg, 47.3% at 125 mg and 49.9% at 200 mg. Estimated ED(50) was 122.5 mg with the dose for 5-HTT and 149.9 mg for NET. Both 5-HTT and NET occupa

Link information
DOI
https://doi.org/10.1017/s1461145712001009
DOI
https://doi.org/10.1017/S1461145712001009
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/23067569
ID information
  • DOI : 10.1017/s1461145712001009
  • DOI : 10.1017/S1461145712001009
  • ISSN : 1469-5111
  • ORCID - Put Code : 100970571
  • Pubmed ID : 23067569

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