Enhanced norepinephrine output during long-term desipramine treatment

A possible role for the extraneuronal monoamine transporter (SLC22A3)

John J. Mooney, Jacqueline A. Samson, John Hennen, Kathleen Pappalardo, Nancy McHale, Jonathan E. Alpert, Martha Koutsos, Joseph J. Schildkraut

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

To study the delay (2-6 weeks) between initial administration of norepinephrine reuptake inhibitor antidepressants and onset of clinical antidepressant action, we examined the effects of desipramine treatment on urinary and plasma catecholamines and their metabolites during the initial 6 weeks of treatment in depressed patients. Catecholamines and metabolites in 24-h urine collections and 8:00 a.m. plasma samples were measured at baseline and after 1, 4, and 6 weeks of desipramine treatment. Desipramine treatment produced significant increases in urinary norepinephrine (NE) and normetanephrine (NMN) and plasma NE at Weeks 4 and 6, but not at Week 1. The ratio of urinary NE/NMN was increased at Weeks 4 and 6, suggesting a reduction in the metabolism of NE to NMN at extraneuronal sites by Weeks 4 and 6. The increases in urinary NE and NMN and plasma NE at Weeks 4 and 6 of desipramine treatment were associated with a reduction in the conversion of NE to NMN. This would be compatible with a blockade of the extraneuronal monoamine transporter (organic cation transporter 3; SLC22A3) by NMN. Inhibition of the extraneuronal monoamine transporter may be an important component in the clinical pharmacology of the norepinephrine reuptake inhibitor antidepressant drugs, such as desipramine. The ClinicalTrials.gov Identifier for this study is NCT00320632.

Original languageEnglish (US)
Pages (from-to)605-611
Number of pages7
JournalJournal of Psychiatric Research
Volume42
Issue number8
DOIs
StatePublished - Jul 2008
Externally publishedYes

Fingerprint

Desipramine
Normetanephrine
Norepinephrine
Antidepressive Agents
Therapeutics
Catecholamines
Urine Specimen Collection
Clinical Pharmacology
Cations

Keywords

  • Depression
  • Desipramine
  • Extraneuronal monoamine transporter
  • Norepinephrine
  • SLC22A3

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry
  • Psychology(all)

Cite this

Enhanced norepinephrine output during long-term desipramine treatment : A possible role for the extraneuronal monoamine transporter (SLC22A3). / Mooney, John J.; Samson, Jacqueline A.; Hennen, John; Pappalardo, Kathleen; McHale, Nancy; Alpert, Jonathan E.; Koutsos, Martha; Schildkraut, Joseph J.

In: Journal of Psychiatric Research, Vol. 42, No. 8, 07.2008, p. 605-611.

Research output: Contribution to journalArticle

Mooney, John J. ; Samson, Jacqueline A. ; Hennen, John ; Pappalardo, Kathleen ; McHale, Nancy ; Alpert, Jonathan E. ; Koutsos, Martha ; Schildkraut, Joseph J. / Enhanced norepinephrine output during long-term desipramine treatment : A possible role for the extraneuronal monoamine transporter (SLC22A3). In: Journal of Psychiatric Research. 2008 ; Vol. 42, No. 8. pp. 605-611.
@article{da8eb7063b8e495ca18db7f3f9609588,
title = "Enhanced norepinephrine output during long-term desipramine treatment: A possible role for the extraneuronal monoamine transporter (SLC22A3)",
abstract = "To study the delay (2-6 weeks) between initial administration of norepinephrine reuptake inhibitor antidepressants and onset of clinical antidepressant action, we examined the effects of desipramine treatment on urinary and plasma catecholamines and their metabolites during the initial 6 weeks of treatment in depressed patients. Catecholamines and metabolites in 24-h urine collections and 8:00 a.m. plasma samples were measured at baseline and after 1, 4, and 6 weeks of desipramine treatment. Desipramine treatment produced significant increases in urinary norepinephrine (NE) and normetanephrine (NMN) and plasma NE at Weeks 4 and 6, but not at Week 1. The ratio of urinary NE/NMN was increased at Weeks 4 and 6, suggesting a reduction in the metabolism of NE to NMN at extraneuronal sites by Weeks 4 and 6. The increases in urinary NE and NMN and plasma NE at Weeks 4 and 6 of desipramine treatment were associated with a reduction in the conversion of NE to NMN. This would be compatible with a blockade of the extraneuronal monoamine transporter (organic cation transporter 3; SLC22A3) by NMN. Inhibition of the extraneuronal monoamine transporter may be an important component in the clinical pharmacology of the norepinephrine reuptake inhibitor antidepressant drugs, such as desipramine. The ClinicalTrials.gov Identifier for this study is NCT00320632.",
keywords = "Depression, Desipramine, Extraneuronal monoamine transporter, Norepinephrine, SLC22A3",
author = "Mooney, {John J.} and Samson, {Jacqueline A.} and John Hennen and Kathleen Pappalardo and Nancy McHale and Alpert, {Jonathan E.} and Martha Koutsos and Schildkraut, {Joseph J.}",
year = "2008",
month = "7",
doi = "10.1016/j.jpsychires.2007.07.009",
language = "English (US)",
volume = "42",
pages = "605--611",
journal = "Journal of Psychiatric Research",
issn = "0022-3956",
publisher = "Elsevier Limited",
number = "8",

}

TY - JOUR

T1 - Enhanced norepinephrine output during long-term desipramine treatment

T2 - A possible role for the extraneuronal monoamine transporter (SLC22A3)

AU - Mooney, John J.

AU - Samson, Jacqueline A.

AU - Hennen, John

AU - Pappalardo, Kathleen

AU - McHale, Nancy

AU - Alpert, Jonathan E.

AU - Koutsos, Martha

AU - Schildkraut, Joseph J.

PY - 2008/7

Y1 - 2008/7

N2 - To study the delay (2-6 weeks) between initial administration of norepinephrine reuptake inhibitor antidepressants and onset of clinical antidepressant action, we examined the effects of desipramine treatment on urinary and plasma catecholamines and their metabolites during the initial 6 weeks of treatment in depressed patients. Catecholamines and metabolites in 24-h urine collections and 8:00 a.m. plasma samples were measured at baseline and after 1, 4, and 6 weeks of desipramine treatment. Desipramine treatment produced significant increases in urinary norepinephrine (NE) and normetanephrine (NMN) and plasma NE at Weeks 4 and 6, but not at Week 1. The ratio of urinary NE/NMN was increased at Weeks 4 and 6, suggesting a reduction in the metabolism of NE to NMN at extraneuronal sites by Weeks 4 and 6. The increases in urinary NE and NMN and plasma NE at Weeks 4 and 6 of desipramine treatment were associated with a reduction in the conversion of NE to NMN. This would be compatible with a blockade of the extraneuronal monoamine transporter (organic cation transporter 3; SLC22A3) by NMN. Inhibition of the extraneuronal monoamine transporter may be an important component in the clinical pharmacology of the norepinephrine reuptake inhibitor antidepressant drugs, such as desipramine. The ClinicalTrials.gov Identifier for this study is NCT00320632.

AB - To study the delay (2-6 weeks) between initial administration of norepinephrine reuptake inhibitor antidepressants and onset of clinical antidepressant action, we examined the effects of desipramine treatment on urinary and plasma catecholamines and their metabolites during the initial 6 weeks of treatment in depressed patients. Catecholamines and metabolites in 24-h urine collections and 8:00 a.m. plasma samples were measured at baseline and after 1, 4, and 6 weeks of desipramine treatment. Desipramine treatment produced significant increases in urinary norepinephrine (NE) and normetanephrine (NMN) and plasma NE at Weeks 4 and 6, but not at Week 1. The ratio of urinary NE/NMN was increased at Weeks 4 and 6, suggesting a reduction in the metabolism of NE to NMN at extraneuronal sites by Weeks 4 and 6. The increases in urinary NE and NMN and plasma NE at Weeks 4 and 6 of desipramine treatment were associated with a reduction in the conversion of NE to NMN. This would be compatible with a blockade of the extraneuronal monoamine transporter (organic cation transporter 3; SLC22A3) by NMN. Inhibition of the extraneuronal monoamine transporter may be an important component in the clinical pharmacology of the norepinephrine reuptake inhibitor antidepressant drugs, such as desipramine. The ClinicalTrials.gov Identifier for this study is NCT00320632.

KW - Depression

KW - Desipramine

KW - Extraneuronal monoamine transporter

KW - Norepinephrine

KW - SLC22A3

UR - http://www.scopus.com/inward/record.url?scp=43049145040&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=43049145040&partnerID=8YFLogxK

U2 - 10.1016/j.jpsychires.2007.07.009

DO - 10.1016/j.jpsychires.2007.07.009

M3 - Article

VL - 42

SP - 605

EP - 611

JO - Journal of Psychiatric Research

JF - Journal of Psychiatric Research

SN - 0022-3956

IS - 8

ER -