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Markku Linnoila, MD, PhD; Farouk Karoum, PhD; Helena M. Calil, MD, PhD; Irwin J. Kopin, MD; William Z. Potter, MD, PhD

Arch Gen Psychiatry. 1982;39(9):1025-1028.

Abstract
• Twelve patients with a major affective disorder were treated during the depressed phase of their illness with desipramine hydrochloride and/or zimelidine hydrochloride, and urinary excretion rates of norepinephrine and its major metabolites were examined. During treatment with desipramine, daily urinary excretion of norepinephrine, 3-methoxy-4-hydroxyphenylglycol (MHPG), and vanillylmandelic acid was reduced, but urinary normetanephrine excretion was not significantly changed. In all patients, the proportion of urinary norepinephrine metabolites represented by normetanephrine was increased during desipramine treatment. Independent of treatment outcome, desipramine seemed to decrease total formation and metabolism of norepinephrine, which was reflected in decreases in the excretion rate of the catecholamine and its metabolites. These results are consistent with known actions of desipramine on the disposition of norepinephrine and represent alterations in the rate of norepinephrine formation and metabolism, resulting from inhibition of norepinephrine reuptake. Zimelidine, a new antidepressant, which is a relatively specific serotonin-reuptake inhibitor, significantly reduced only urinary MHPG excretion without appearing to alter "whole-body" norepinephrine turnover. This effect of zimelidine on norepinephrine metabolism was unexpected. Current and previous findings concerning clorgyline, a relatively specific monoamine oxidase A inhibitor, suggest that three pharmacologically distinct classes of antidepressants, norepinephrine and serotonin-reuptake and monoamine oxidase type A inhibitors, all reduce central norepinephrine turnover in depressed patients.

Author Affiliations
From the Clinical Psychobiology (Drs Linnoila, Calil, and Potter) and Adult Psychiatry (Dr Karoum) Branches and Laboratory of Clinical Science (Dr Kopin), National Institute of Mental Health, Bethesda, Md.

Footnotes
Accepted for publication March 3, 1982.

Reprint requests to Clinical Psychobiology Branch, National Institute of Mental Health, 9000 Rockville Pike, Bethesda, MD 20205 (Dr Linnoila).

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