Clinical Implications of the Tricyclic Antidepressant Hydroxy-Metabolites

  • J. Craig Nelson
Chapter

Abstract

Metabolism of the tricyclic antidepressants results in the production of hydroxylated compounds (OH-TCAs) that are then conjugated and excreted. Although concentrations of hydroxyimipramine and hydroxyamitriptyline are low in human subjects relative to their parent compounds, levels of 2-hydroxydesipramine (OH-DMI) are commonly half that of DMI and levels of 10-hydroxynortriptyline (OH-NOR) are comparable to that of the parent compound. In some individuals plasma concentrations of OH-NOR and OH-DMI exceed those of the parent drug. OH-TCAs appear to be less protein-bound in plasma than their parent compounds, and the OH-DMI/DMI and OH-NOR/NOR ratios are higher in cerebrospinal fluid (CSF) than in plasma. Thus OH-DMI and OH-NOR are present in appreciable levels in plasma and CSF and, if active, could contribute to the clinical effects of the TCAs. During the late 1970s it was demonstrated that the OH-TCAs block reuptake of norepinephrine and serotonin and that they have behavioral effects in animals similar to those of the TCAs, but it was not clear that they have antidepressant effects.

Keywords

Depression Serotonin Norepinephrine Acetylcholine Tricyclic 

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© Springer-Verlag New York Inc. 1989

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  • J. Craig Nelson

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