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Effects of Tricyclic Antidepressants on Norepinephrine Metabolism: Basic and Clinical Studies

  • Joseph J. Schildkraut
  • Paul R. Draskoczy
  • Elliot S. Gershon
  • Peter Reich
  • Edwin L. Grab
Part of the Advances in Behavioral Biology book series (ABBI, volume 1)

Abstract

The tricyclic antidepressants have been well established as clinically effective treatments for certain types of depressions, and these drugs have provided important tools for investigating those neurochemical changes that may be associated with alterations in affective state in man (Schildkraut 1970). Some years ago, in clinical studies of depressed patients, we observed a decrease in the urinary excretion of 3-methoxy-4-hydroxymandelic acid (VMA), the major deaminated O-methylated metabolite of norepinephrine during treatment with imipramine (a tricyclic antidepressant) as well as with phenelzine (a monoamine oxidase inhibitor) (Table 1) (Schildkraut et al. 1964; Schildkraut, Gordon, and Durell 1965). In these studies with imipramine, we showed that the decrease in VMA excretion was a pharmacological effect of the drug per se and not a secondary concomitant of the alteration in clinical state (Table 2) (Schildkraut, Gordon, and Durell 1965). On the basis of these findings, which have been confirmed by other investigators (Haskovec and Rysanek 1967; Maas, Fawcett, and Dekirmenjian 1968b and personal communication), we suggested that tricyclic antidepressants like monoamine oxidase inhibitors may decrease the deamination of norepinephrine. Subsequently, Glowinski, Axelrod, and Iversen (1966) showed that desmethylimipramine decreased the deamination of intraventricularly administered tritiated norepinephrine in rat brain, and we found a similar decrease in the deamination of intracisternally administered tritiated norepinephrine and a concurrent increase in levels of tritiated normetanephrine in rat brain after administration of various other tricyclic antidepressants (Table 3) (Schildkraut et al. 1967; Schildkraut, Dodge, and Logue 1969).

Keywords

Depressed Patient Biogenic Amine Intracisternal Injection Norepinephrine Synthesis MHPG Level 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1971

Authors and Affiliations

  • Joseph J. Schildkraut
    • 1
    • 2
  • Paul R. Draskoczy
    • 1
    • 2
  • Elliot S. Gershon
    • 1
    • 2
  • Peter Reich
    • 1
    • 2
  • Edwin L. Grab
    • 1
    • 2
  1. 1.Massachusetts Mental Health CenterBostonUSA
  2. 2.Harvard Medical SchoolBostonUSA

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