Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phenelzine (PLZ), a nonselective monoamine oxidase inhibitor, is widely used in psychiatry for the treatment of panic disorder and depression. The effects of chronic (28-day) administration of PLZ (0.05 mmol/kg/day) and its N-acetylated analogue, 1-acetyl-2-(2-phenylethyl) hydrazine (N2-acetylphenelzine; N2AcPLZ; 0.10 mmol/kg/day), on alpha 2-adrenoreceptor function were investigated by use of a behavioral test on days 21 and 22. Rats treated with PLZ or N2AcPLZ displayed a significant attenuation of the suppressant effects of clonidine on spontaneous locomotor activity, compared with controls; these results suggest a reduced sensitivity of alpha 2-adrenoreceptors. By day 28, both PLZ and N2AcPLZ had produced greater than 85% inhibition of monoamine oxidases A and B in the brain, heart, and liver. Both drugs induced significant elevations of whole-brain levels of noradrenaline, 5-hydroxytryptamine, and dopamine, compared with those in controls. The levels of acid metabolites of dopamine and 5-hydroxytryptamine (homovanillic acid, 3,4-dihydroxyphenylacetic acid, and 5-hydroxyindole-3-acetic acid) were significantly reduced in both groups of drug-treated animals.
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PMID:Chronic administration of the antidepressant-antipanic drug phenelzine and its N-acetylated analogue: effects on monoamine oxidase, biogenic amines, and alpha 2-adrenoreceptor function. 138 93

Long-term treatment with antidepressant drugs has received little attention until recently. A study is reported comparing the effectiveness of maintenance treatment with phenelzine in responding major depression patients. If they responded initially to nonblind phenelzine treatment and sustained remission for 16 weeks, patients were randomized to 2-year double-blind treatment with phenelzine 60 mg/day, phenelzine 45 mg/day, or placebo. Both doses of phenelzine were significantly better than placebo in preventing relapse of depression. Phenelzine 45 mg/day may be an optimal maintenance dose for many patients.
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PMID:Continuation and maintenance treatment of major depression with the monoamine oxidase inhibitor phenelzine: a double-blind placebo-controlled discontinuation study. 186 4

A trial is described of new therapeutic approaches in treatment-resistant chronic depression. Phenelzine, L-tryptophan and lithium ("5HT-cocktail") was used as the major pharmacological strategy, and a regime aimed at reducing vanadium concentrations was added in the second part of the trial. Patients were randomly assigned to cognitive behaviour therapy in addition. All but 1 of the patients who ultimately entered the trial were unipolar depressives; 2 bipolar patients were withdrawn in the initial drug-free period because of the development of mixed affective states. Eleven of 20 patients showed an improvement to less than 50% of their initial scores on the Hamilton Rating Scale for Depression, and all those who improved did so in the first 6 weeks. Cognitive behaviour therapy did not seem to influence the response, but it is recognized that the short duration of therapy may be inadequate in these circumstances. It is suggested that intensive drug treatment is a necessary preliminary in management and may allow the effective use of rehabilitation aimed at the secondary handicaps of chronic depression.
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PMID:The Newcastle chronic depression study: results of a treatment regime. 312 18

One hundred nineteen patients who met specific criteria for atypical depression completed six weeks of double-blind, randomly assigned treatment with phenelzine sulfate, imipramine hydrochloride, or placebo. The overall response rates were 71% with phenelzine, 50% with imipramine, and 28% with placebo. Phenelzine was widely superior to placebo and also showed superiority to imipramine. Phenelzine superiority appeared even greater after an additional six-week continuation phase. Imipramine was only moderately effective in this atypical depressive sample. Unexpectedly, the superiority of either phenelzine or imipramine to placebo was largely confined to patients in subsets of the study sample who were prospectively judged to also have a history of spontaneous panic attacks and/or show hysteroid dysphoric features. This is consonant with some but not other recent findings and requires replication. Overall, the concept of atypical depression as a subtype that is preferentially responsive to monoamine oxidase inhibitors is supported.
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PMID:Antidepressant specificity in atypical depression. 327 82

Sixty patients with probable atypical depression--defined as meeting Research Diagnostic Criteria for depressive illness, having reactive mood, and having one of four associated symptoms (hyperphagia, hypersomnolence, leaden feeling, and sensitivity to rejection)--took part in a study contrasting phenelzine, imipramine, and placebo. Phenelzine was found to be superior to imipramine and placebo. These results were compared to results from a sample of 120 patients with identical characteristics, except that they had more than one associated atypical symptom (full atypical syndrome). The size of the drug effect was comparable in patients with full atypical and partial atypical syndromes.
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PMID:Phenelzine versus imipramine in the treatment of probable atypical depression: defining syndrome boundaries of selective MAOI responders. 327 31

Phenelzine and imipramine were evaluated in a 5-week double-blind study of outpatients with major depression. Median daily doses of phenelzine 75 mg and imipramine 150 mg were employed. Of 27 patients 26 completed the 5-week study. Both drugs produced an equal overall effect, as measured by the Hamilton Rating Scale for Depression (HAM-D) and the Beck Depression Inventory (BDI). When patients were grouped on the basis of panic attack symptoms, phenelzine was found to be more effective than imipramine (p less than .05 for all patients on the BDI; p less than .05 for women on both rating scales).
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PMID:An outpatient evaluation of phenelzine and imipramine. 354 5

Sixty patients meeting specific criteria for atypical depression completed six weeks of double-blind, randomly assigned treatment with phenelzine sulfate, imipramine hydrochloride, or placebo. The overall response rates were 67% with phenelzine, 43% with imipramine, and 29% with placebo. At week 6, phenelzine was superior to placebo on many measures, while the superiority of imipramine to placebo was confined to several variables. Phenelzine was superior to imipramine on the interpersonal sensitivity and paranoia factors of the 90-item Hopkins Symptom Checklist, with trends toward superiority on several other measures, while imipramine was not differentially superior on any measure. Atypical depressive patients with a history of spontaneous panic attacks and hysteroid dysphoric patients both showed extremely low rates of response to placebo and high rates of response to phenelzine. Conversely, those without panic or hysteroid dysphoric features responded equally to all three treatments. Responders to pheneizine also had greater platelet monoamine oxidase inhibition while receiving drug therapy than did nonresponders. Completion of the 120-patient sample will allow more detailed analyses.
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PMID:Phenelzine v imipramine in atypical depression. A preliminary report. 637 21

Phenelzine and imipramine were compared double-blind, in 43 depressed inpatients. A placebo week preceded drug treatment; this allowed early identification of placebo responders who did not therefore enter the study. After three weeks treatment, the two drugs were equally effective on Hamilton, Beck and SCL-90 measures of depression and anxiety. On the the SCL-90 scales of hostility and paranoia imipramine was more effective; in some patients phenelzine was associated with increased hostility. Measurement of MAO inhibition and plasma tricyclic levels indicated that adequate doses were generally used - (mean 81 mg/day phenelzine and 144 mg/day imipramine).
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PMID:A comparison of phenelzine and imipramine in depressed inpatients. 702 42

The monoamine oxidase inhibitors (MAOIs) have been used increasingly in treating nonendogenous depressions. Patients with psychophysiologic disorders have many characteristics in common with known MAOI responders. The authors present the case of a man who had had diarrhea for 36 years, with an underlying chronic depression. The patient was unresponsive to ECT and tricyclic antidepressants. Phenelzine, 60 mg/day, produced dramatic improvement in the patient's diarrhea and his sense of well-being.
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PMID:Phenelzine treatment of depression with chronic diarrhea. 708 81

1. The binding of [3H]-idazoxan in the presence of 10(-6) M (-)-adrenaline was used to quantitate I2 imidazoline-preferring receptors in the rat brain and liver after chronic treatment with various irreversible and reversible monoamine oxidase (MAO) inhibitors. 2. Chronic treatment (7-14 days) with the irreversible MAO inhibitors, phenelzine (1-20 mg kg-1, i.p.), isocarboxazid (10 mg kg-1, i.p.), clorgyline (3 mg kg-1, i.p.) and tranylcypromine (10 mg kg-1, i.p.) markedly decreased (21-71%) the density of I2 imidazoline-preferring receptors in the rat brain and liver. In contrast, chronic treatment (7 days) with the reversible MAO-A inhibitors, moclobemide (1 and 10 mg kg-1, i.p.) or chlordimeform (10 mg kg-1, i.p.) or with the reversible MAO-B inhibitor Ro 16-6491 (1 and 10 mg kg-1, i.p.) did not alter the density of I2 imidazoline-preferring receptors in the rat brain and liver; except for the higher dose of Ro 16-6491 which only decreased the density of these putative receptors in the liver (38%). 3. In vitro, phenelzine, clorgyline, 3-phenylpropargylamine, tranylcypromine and chlordimeform displaced the binding of [3H]-idazoxan to brain and liver I2 imidazoline-preferring receptors from two distinct binding sites. Phenelzine, 3-phenylpropargylamine and tranylcypromine displayed moderate affinity (KiH = 0.3-6 microM) for brain and liver I2 imidazoline-preferring receptors; whereas chlordimeform displayed high affinity (KiH = 6 nM) for these receptors in the two tissues studied, Clorgyline displayed very high affinity for rat brain (KiH = 40 pM) but not for rat liver I2 imidazoline-preferring receptors (KiH = 169 nM). 4. Preincubation of cortical or liver membranes with phenelzine (10-4 M for 30 min) did not alter the total density of I2 imidazoline-preferring receptors, indicating that this irreversible MAO inhibitor does not irreversibly bind to I2 imidazoline-preferring receptors. In contrast, preincubation with 10-6 Mclorgyline reduced by 40% the Bmax of [3H]-idazoxan to brain and liver I2 imidazoline-preferring receptors.5. Chronic treatment (7 days) with the inducers of cytochrome P-450 enzymes phenobarbitone (40 or 80 mg kg-1, i.p.), 3-methylcholanthrene (20 mg kg-1, i.p.) or 2-methylimidazole (40 mg kg-1, i.p.) did not alter the binding parameters of [3H]-idazoxan to brain and liver 12 imidazoline-preferring receptors.The compound SKF 525A, a potent inhibitor of cytochrome P-450 enzymes which forms a tight but reversible complex with the haemoprotein, completely displaced with moderate affinity (KiH = 2-10 microM)the specific binding of [3H]-idazoxan to brain and liver 12 imidazoline-preferring receptors. Preincubation of total liver homogenates with 3 x 10-4 M phenelzine in the presence of 10-3 M NADH, a treatment that irreversibly inactivates the haeme group of cytochrome P-450, did not reduce the density of liver I2 imidazoline-preferring receptors. These results discounted a possible interaction of [3H]-idazoxan with the haeme group of cytochrome P-450 enzymes.6. Together the results indicate that the down-regulation of I2 imidazoline-preferring receptors is associated with an irreversible inactivation of MAO (at least in the brain) that is not related either to the affinity of the MAO inhibitors for I2 imidazoline-preferring receptors or to an irreversible binding to these putative receptors. These findings indicate a novel effect of irreversible MAO inhibitors in the brain and suggest a new target for these compounds that could be of relevance in the treatment of depression, a disease in which an increased density of brain I2 imidazoline-preferring receptors has been reported.
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PMID:The effects of phenelzine and other monoamine oxidase inhibitor antidepressants on brain and liver I2 imidazoline-preferring receptors. 777 44


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