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
AU - Koutsos, Martha
AU - Schildkraut, Joseph J.
N1 - Funding Information:
Funding for this study was provided by NIMH Grant Number MH-15413. The NIMH had no further role in study design, in the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the paper for publication.
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
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U2 - 10.1016/j.jpsychires.2007.07.009
DO - 10.1016/j.jpsychires.2007.07.009
M3 - Article
C2 - 17727882
AN - SCOPUS:43049145040
SN - 0022-3956
VL - 42
SP - 605
EP - 611
JO - Journal of Psychiatric Research
JF - Journal of Psychiatric Research
IS - 8
ER -
