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- Title
Occupancy of serotonin and norepinephrine transporter by milnacipran in patients with major depressive disorder: a positron emission tomography study with [11C]DASB and (S,S)-[18F]FMeNER-D2.
- Authors
Nogami, Tsuyoshi; Takano, Harumasa; Arakawa, Ryosuke; Ichimiya, Tetsuya; Fujiwara, Hironobu; Kimura, Yasuyuki; Kodaka, Fumitoshi; Sasaki, Takeshi; Takahata, Keisuke; Suzuki, Masayuki; Nagashima, Tomohisa; Mori, Takaaki; Shimada, Hitoshi; Fukuda, Hajime; Sekine, Mizuho; Tateno, Amane; Takahashi, Hidehiko; Ito, Hiroshi; Okubo, Yoshiro; Suhara, Tetsuya
- Abstract
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 [11C]DASB and (S,S)-[18F]FMeNER-D2, 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 ED50 was 122.5 mg with the dose for 5-HTT and 149.9 mg for NET. Both 5-HTT and NET occupancies were observed in a dose-dependent manner. Both 5-HTT and NET occupancies were about 40% by milnacipran at 100 mg, the dose most commonly administered to MDD patients.
- Subjects
SEROTONIN; NORADRENERGIC mechanisms; MENTAL depression; POSITRON emission tomography; ANTIDEPRESSANTS; SEROTONIN transporters; DRUG dosage; RADIOLIGAND assay
- Publication
International Journal of Neuropsychopharmacology, 2013, Vol 16, Issue 5, p937
- ISSN
1461-1457
- Publication type
Article
- DOI
10.1017/S1461145712001009