Norepinephrine transporter occupancy by nortriptyline in patients with depression

A positron emission tomography study with (S,S)-[ 18F]FMeNER-D2

Harumasa Takano, Ryosuke Arakawa, Tsuyoshi Nogami, Masayuki Suzuki, Tomohisa Nagashima, Hironobu Fujiwara, Yasuyuki Kimura, Fumitoshi Kodaka, Keisuke Takahata, Hitoshi Shimada, Yoshitaka Murakami, Amane Tateno, Makiko Yamada, Hiroshi Ito, Kazunori Kawamura, Ming Rong Zhang, Hidehiko Takahashi, Motoichiro Kato, Yoshiro Okubo, Tetsuya Suhara

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Norepinephrine transporter (NET) plays important roles in the treatment of various neuropsychiatric disorders, such as depression and attention deficit hyperactivity disorder (ADHD). Nortriptyline is a NET-selective tricyclic antidepressant (TCAs) that has been widely used for the treatment of depression. Previous positron emission tomography (PET) studies have reported over 80% serotonin transporter occupancy with clinical doses of selective serotonin reuptake inhibitors (SSRIs), but there has been no report of NET occupancy in patients treated with relatively NET-selective antidepressants. In the present study, we used PET and (S,S)-[18F]FMeNER-D2 to investigate NET occupancies in the thalamus in 10 patients with major depressive disorder taking various doses of nortriptyline, who were considered to be responders to the treatment. Reference data for the calculation of occupancy were derived from age-matched healthy controls. The result showed approximately 50-70% NET occupancies in the brain as a result of the administration of 75-200 mg/d of nortriptyline. The estimated effective dose (ED50) and concentration (EC50) required to induce 50% occupancy was 65.9 mg/d and 79.8 ng/ml, respectively. Furthermore, as the minimum therapeutic level of plasma nortriptyline for the treatment of depression has been reported to be 70 ng/ml, our data indicate that this plasma nortriptyline concentration corresponds to approximately 50% NET occupancy measured with PET, suggesting that more than 50% of central NET occupancy would be appropriate for the nortriptyline treatment of patients with depression.

Original languageEnglish
Pages (from-to)553-560
Number of pages8
JournalInternational Journal of Neuropsychopharmacology
Volume17
Issue number4
DOIs
Publication statusPublished - 2014

Fingerprint

Norepinephrine Plasma Membrane Transport Proteins
Nortriptyline
Positron-Emission Tomography
Depression
Therapeutics
Serotonin Plasma Membrane Transport Proteins
2-(alpha-(2-fluoromethoxyphenoxy)benzyl)morpholine
Tricyclic Antidepressive Agents
Major Depressive Disorder
Serotonin Uptake Inhibitors
Attention Deficit Disorder with Hyperactivity
Thalamus
Antidepressive Agents

Keywords

  • Depression
  • norepinephrine transporter
  • nortriptyline
  • occupancy
  • positron emission tomography

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Psychiatry and Mental health
  • Medicine(all)

Cite this

Norepinephrine transporter occupancy by nortriptyline in patients with depression : A positron emission tomography study with (S,S)-[ 18F]FMeNER-D2. / Takano, Harumasa; Arakawa, Ryosuke; Nogami, Tsuyoshi; Suzuki, Masayuki; Nagashima, Tomohisa; Fujiwara, Hironobu; Kimura, Yasuyuki; Kodaka, Fumitoshi; Takahata, Keisuke; Shimada, Hitoshi; Murakami, Yoshitaka; Tateno, Amane; Yamada, Makiko; Ito, Hiroshi; Kawamura, Kazunori; Zhang, Ming Rong; Takahashi, Hidehiko; Kato, Motoichiro; Okubo, Yoshiro; Suhara, Tetsuya.

In: International Journal of Neuropsychopharmacology, Vol. 17, No. 4, 2014, p. 553-560.

Research output: Contribution to journalArticle

Takano, H, Arakawa, R, Nogami, T, Suzuki, M, Nagashima, T, Fujiwara, H, Kimura, Y, Kodaka, F, Takahata, K, Shimada, H, Murakami, Y, Tateno, A, Yamada, M, Ito, H, Kawamura, K, Zhang, MR, Takahashi, H, Kato, M, Okubo, Y & Suhara, T 2014, 'Norepinephrine transporter occupancy by nortriptyline in patients with depression: A positron emission tomography study with (S,S)-[ 18F]FMeNER-D2', International Journal of Neuropsychopharmacology, vol. 17, no. 4, pp. 553-560. https://doi.org/10.1017/S1461145713001521
Takano, Harumasa ; Arakawa, Ryosuke ; Nogami, Tsuyoshi ; Suzuki, Masayuki ; Nagashima, Tomohisa ; Fujiwara, Hironobu ; Kimura, Yasuyuki ; Kodaka, Fumitoshi ; Takahata, Keisuke ; Shimada, Hitoshi ; Murakami, Yoshitaka ; Tateno, Amane ; Yamada, Makiko ; Ito, Hiroshi ; Kawamura, Kazunori ; Zhang, Ming Rong ; Takahashi, Hidehiko ; Kato, Motoichiro ; Okubo, Yoshiro ; Suhara, Tetsuya. / Norepinephrine transporter occupancy by nortriptyline in patients with depression : A positron emission tomography study with (S,S)-[ 18F]FMeNER-D2. In: International Journal of Neuropsychopharmacology. 2014 ; Vol. 17, No. 4. pp. 553-560.
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T2 - A positron emission tomography study with (S,S)-[ 18F]FMeNER-D2

AU - Takano, Harumasa

AU - Arakawa, Ryosuke

AU - Nogami, Tsuyoshi

AU - Suzuki, Masayuki

AU - Nagashima, Tomohisa

AU - Fujiwara, Hironobu

AU - Kimura, Yasuyuki

AU - Kodaka, Fumitoshi

AU - Takahata, Keisuke

AU - Shimada, Hitoshi

AU - Murakami, Yoshitaka

AU - Tateno, Amane

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AU - Ito, Hiroshi

AU - Kawamura, Kazunori

AU - Zhang, Ming Rong

AU - Takahashi, Hidehiko

AU - Kato, Motoichiro

AU - Okubo, Yoshiro

AU - Suhara, Tetsuya

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