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Dihydroxy-phenyl-ethylene-glycol (DOPEG or DHPG), a deaminated catabolite of noradrenaline formed after presynaptic re-uptake, is a good marker of metabolic activity in noradrenergic pathways. Plasma levels of free, conjugated and total DOPEG were measured by a radioenzymatic method in 45 patients with major depression selected according to the DSM 3 criteria and in 45 matched controls. A significant decrease in man DOPEG levels was observed in all depressive patients. A dexamethasone suppression test performed in these patients showed no difference in DOPEG levels between responders and non-responders, thus failing to support the hypothesis that subjects with low noradrenergic drive escape suppression. There was no correlation between plasma DOPEG levels and urinary excretion of methoxy-hydroxy-phenylglycol (MOPEG), another marker of noradrenaline metabolic activity. Thirty-one patients were treated with a specific monoaminergic antidepressant: maprotiline or indalpine; contrary to urinary MOPEG levels, plasma DOPEG levels had no predictive value concerning the response to this category of antidepressants. The various possible reasons for the fall in DOPEG observed in depressive patients are discussed.

Cimoxatone is a new monoamine oxidase inhibitor (MAOI) in comparison to the existing non-selective and irreversible MAOIs used in the therapy of depression. A clinical study has been carried out in 10 depressed patients. Cimoxatone was given from 0.32 to 0.78 mg/kg/day for 28 days. The drug was shown to be effective against depression and well tolerated at the given doses. The inhibition of monoamine oxidase and its reversibility were assessed by urinary excretion of 3-methoxy-4-hydroxy- phenylethyleneglycol sulphate. The treatment had no effect on the plasma prolactin levels. The plasma concentrations of cimoxatone reached a plateau after 3 to 4 days of therapy. The study confirmed earlier findings in healthy volunteers that the principal metabolite is also active as a type A MAOI. The plasma elimination of cimoxatone and its metabolite is almost complete 4 days after the last dosing.

Some biochemical assays are available to test the central NA activity in depressed patients. In several laboratories, two metabolites of NA, namely DHPG and MHPG, in either free, conjugated or total form, have been assayed indifferently for this purpose. The present report shows positive correlations between the level of the two glycols, as well as between their different forms in the plasma. In contrast, the level of erythrocyte COMT activity was not correlated with plasma MHPG, and did not show any change during the treatment with respect to the control pretreatment period in depressed patients. The values of MHPG showed a bimodal distribution in the patients before treatment; the plasma level of this metabolite decreased significantly in the first month of treatment, but did not change subsequently. The COMT activity values, as well as MHPG, were significantly correlated between the different time points, that is the control period and after 1 to 3 months of treatment.

The determination of urinary MHPG (3-methoxy-4-hydroxyphenyl glycol) has been extensively performed to confirm the noradrenergic hypothesis of some depressions. However, owing to the double origin, central and peripheral, of this norepinephrine metabolite, the validity of total MHPG assay as an index of central noradrenergic activity may be challenged. MHPG exists in human urine in two conjugated forms, at equal amounts: sulfate and glucuronide. A number of arguments suggest that MHPG sulfate and MHPG glucuronide respectively reflect central and peripheral norepinephrine metabolism. In this work, we have selectively estimated both MHPG conjugates in 24 h-urine samples of 36 severely depressed women in view to assess the extent and frequency of central or/and peripheral norepinephrine dysfunction. On the basis of MHPG sulfate and glucuronide values, we conclude that in the examined population (6 endogenous, 19 neurotic, 11 reactive depressions) about 80% of patients exhibited a central NE functional deficit, and many of them had also a diminished sympathetic activity. Clinical symptoms related to psychic factors (melancholia) or associated to sympathetic activity changes (anxiety, retardation) respectively alter sulfate or glucuronide MHPG excretion. These data altogether validate the concept of the independent origin of the two MHPG conjugated and show that their selective assay is able to provide a more satisfactory reflection of the psychobiological state in depressed patients than total MHPG determination.

The plasmatic levels of free, sulfoconjugated and total dihydroxyphenylethyleneglycol (DOPEG), the main deaminated metabolite of noradrenaline, have been measured in thirty DSM3 major depressive inpatients and in thirty healthy controls matched for sex and age. DOPEG levels have been measured by a radioenzymatic assay. Almost fifty per cent of depressed inpatients were D.S.T. non suppressors, thirteen patients were unipolar and thirteen bipolar. Plasmatic DOPEG levels were significantly lower in depressed patients as compared to healthy controls despite a wide interindividual range of DOPEG values. However, the ratio of free over conjugated DOPEG was not statistically different in the two groups. DOPEG levels were slightly higher in the female population of healthy volunteers but not in the depressed patients. In the healthy volunteers, but not in depressed patients, there was a trend for free DOPEG to increase and for conjugated DOPEG to decrease with age. There was no statistical correlation between the DOPEG levels and Hamilton Depression Scores. Also plasmatic DOPEG values were not different in uni or bipolar patients and in DST suppressor or DST non suppressor inpatients. The significance of the decrease of plasmatic DOPEG levels in depressed patients is discussed: this diminution may reflect a deficiency in noradrenaline metabolism in CNS or else may be attributed to other factors e.g. alteration in circadian rhythms, differences in motor activity, in level of anxiety, in sleep and feeding behaviors; cotreatment with benzodiazepine and opiate compounds; monoamine oxidase activity.