zimeldine and Affective-Disorders--Psychotic

Single dose and steady-state pharmacokinetics of zimelidine and desipramine were compared in eight depressed patients who were subjects in a double-blind crossover study. Within the same patient, there was no relationship between the pharmacokinetics of desipramine (pharmacokinetically similar to all other tricyclic antidepressants) and those of zimelidin, a bicyclic antidepressant. The weight-corrected dose of zimelidine gives a reasonable index of the concentration of its active metabolite norzimelidine, which predominates over zimelidine by a ratio of approximately 3 to 1. The variation in steady-state concentration of norzimelidine for a given dose of zimelidine in adults is about twofold and can be reduced by correcting for weight.

Topics: Adolescent; Adult; Affective Disorders, Psychotic; Aged; Antidepressive Agents; Brompheniramine; Desipramine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Pyridines; Zimeldine

NE turnover in depressed patients treated with three drugs which have specifically different primary biochemical effects is compared before and after treatment. Turnover is quantitated as the sum of NE and its major metabolites excreted in the urine using a new mass spectrometric assay. Clorgyline , a MAOI specific for Type A; desipramine, a selective NE uptake inhibitor; and zimelidine, a selective 5HT uptake inhibitor, were used. All three antidepressants, including zimelidine, reduced NE turnover although producing very different effects on the metabolic profile of NE. It remains likely that effects on NE are related to therapeutic effect.

Topics: Adult; Affective Disorders, Psychotic; Antidepressive Agents; Clorgyline; Desipramine; Female; Humans; Male; Methoxyhydroxyphenylglycol; Middle Aged; Norepinephrine; Normetanephrine; Propylamines; Vanilmandelic Acid; Zimeldine

Eight depressed patients with major affective illness were treated with both zimelidine, a selective serotonin-uptake inhibitor, and with desipramine, a selective norepinephrine uptake inhibitor, following a double-blind crossover design. At steady-state the active metabolite of zimelidine, norzimelidine, predominated in the CSF by a factor of 7 to 1 over parent drug. As predicted, even high concentrations of norzimelidine were not associated with decreased 3-methoxy-4-hydroxy-phenylglycol (MHPG) in the CSF. In the same individuals, desipramine concentrations were highly correlated with decreases of MHPG in the CSF. Despite specific effects on monoamine neurotransmitter systems which have been implicated in the control of neuroendocrine secretion, neither drug had consistent effects on plasma cortisol, luteinizing hormone, growth hormone or prolactin. Both drugs had a marked and unexpected common effect on the 24-hour rest-activity cycle. The excess activity during the normal rest period (0--700 hr.) which has been noted in severely depressed individuals was significantly reduced by both the serotonergic zimelidine and the noradrenergic desipramine. These findings suggest that effects on the rest-activity pattern may be a common pathway for antidepressant effect.

Topics: Adolescent; Adult; Affective Disorders, Psychotic; Aged; Behavior; Brompheniramine; Desipramine; Double-Blind Method; Female; Hormones; Humans; Kinetics; Male; Middle Aged; Norepinephrine; Serotonin; Zimeldine

In a double-blind group comparison study of 39 patients with primary depressive illness zimelidine in a dose of 200 mg at night demonstrated the same order of antidepressant efficacy as maprotiline in a dose of 150 mg at night after either two or four weeks treatment measured by the amelioration or final score on the Hamilton Rating Scale (HRS) and on the Montgomery & Asberg Depression Rating Scale (MADRS). Both zimelidine and maprotiline demonstrated significant antidepressant activity at 2 weeks compared with 2 weeks prior treatment with placebo measured by amelioration on HRS (paired t 4.1 P less than 0.001, t 2.7 P less than 0.02) or MADRS (paired t 3.5 P less than 0.005, t 5.1 P less than 0.001). An item analysis of the MADRS showed significantly better sleep and appetite in the maprotiline-treated group compared with the zimelidine-treated group which is in accord with the pharmacology of the two compounds.

Topics: Adult; Affective Disorders, Psychotic; Aged; Anthracenes; Antidepressive Agents; Brompheniramine; Depression; Double-Blind Method; Female; Humans; Male; Maprotiline; Middle Aged; Psychiatric Status Rating Scales; Pyridines; Time Factors; Zimeldine