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)

1. Effects of moclobemide (12.5, 25 and 50 mg/kg), harmaline (10 mg/kg) and clorgyline (10 mg/kg) on monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) were examined ex vivo by a fluorometric method with tyramine (T) and phenylethylamine (PEA) as substrates. Six rat brain areas were dissected for this purpose. 2. Moclobemide had decreased MAO-A activity in all areas examined by a dose-dependent manner; the largest decrease was observed in tuberculum olfactorium and striatum. MAO-B activity after moclobemide had presented some dose-dependently inhibition (about 30 percent at a dose of 50 mg/kg). 3. Harmaline was more potent than moclobemide as MAO-A inhibitor but had left MAO-B activity unchanged. 4. Clorgyline was the most potent of the three drug tested for MAO-A inhibition. MAO-B activity was inhibited at the dose used in these experiments. 5. MAO-A inhibitory properties on tuberculum olfactorium and striatum could be of interest according to some animal models of depression.
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PMID:Effect of moclobemide on rat brain monoamine oxidase A and B: comparison with harmaline and clorgyline. 793 67

Data on a twice-daily dosage schedule with moclobemide in the treatment of depression is limited. In this study, moclobemide 150 mg twice daily (b.i.d.) was compared to two different three-times-daily (t.i.d.) regimens with total daily dosages of 300 and 450 mg, respectively, over a 6-week period. The study was randomized, double-blind, and conducted at three university centers. Efficacy was measured on the Hamilton Depression and Anxiety Rating Scales, on the Zung Scale, and on clinical global impression. Tolerability and safety were assessed through adverse events and vital signs and on clinical global impression. One hundred seventy-eight depressed outpatients were included, and 158 completed the study. The treatment groups were comparable at baseline. No clear differences between the treatment groups could be shown with respect to efficacy. There was, however, a slightly larger decrease in the total HAM-A score in the groups receiving 150 mg b.i.d. and t.i.d. than in the third group. There were no marked differences between the groups with respect to tolerability and safety. Tolerability was rated "good" or "excellent" in 94% of patients, and there was no appreciable change in vital signs in any of the treatment groups. Moclobemide 150 mg b.i.d. is the optimal initial schedule for treatment of depression.
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PMID:Moclobemide twice daily in the treatment of major depressive episode: a double-blind, multicenter comparison with different three-times-daily dosage schedules. 795 80

We report the results of a multicenter, double-blind study conducted in a general practice setting, in which the efficacy and tolerability of moclobemide, a new antidepressant drug of the reversible inhibitor of monoamine oxidase type A class, were compared with those of maprotiline, a noradrenaline reuptake inhibitor often prescribed in the general practice setting. Participating general practitioners were required to make differential diagnoses of depressive disorders according to DSM-III criteria and then quantitatively assess the efficacy of treatment using the Hamilton Depression Rating Scale (HDRS) and the Zung self-rating depression scale (Zung SDS). One hundred thirty outpatients (mean age 48 years) with major depression according to DSM-III were randomized to receive either moclobemide 300 mg or maprotiline 75 mg daily for 4 weeks. From day 8, dosages were increased if necessary up to a maximum of 400 mg of moclobemide or 100 mg of maprotiline. The results showed that moclobemide was as effective as maprotiline (HDRS, Zung SDS); moclobemide appeared to have the same antidepressant and anxiolytic activity, but a stronger drive-enhancing effect. Moclobemide was the better-tolerated drug, producing fewer side effects than maprotiline did: in particular, fewer instances of somnolence and dry mouth. The good tolerability of the compound was confirmed by the qualitative assessments of the study physicians.
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PMID:Comparison of the efficacy and tolerability of moclobemide and maprotiline in depressed patients treated by general practitioners. 795 82

Moclobemide, a novel monoamine oxidase-A reversible inhibitor with demonstrated antidepressive efficacy, was administered double-blind versus imipramine to aged depressive subjects. The two drugs were given for 60 days in increasing doses up to 600 mg for moclobemide and 100 mg for imipramine. Fifteen patients received moclobemide and 15 received imipramine. Psychiatric conditions and symptoms were rated at 0, 7, 14, 30, 45, and 60 days after the beginning of the trial by means of the Scale for the Assessment of Psychoorganic Syndromes, Hamilton Rating Scale for Depression, Rome. Depression Inventory, Hamilton Anxiety Rating Scale, State-Trait Anxiety Inventory-X form, and the Clinical Global Impression Scale. Cognition was tested through the Benton visual retention test at days 0, 30, and 60 and the Digit Substitution Test of the Wechsler Adult Intelligence Scale at days 0 and 60. Side effects were assessed through the Dosage Record Emergent Symptoms at days 0, 7, 14, 30, 45, and 60. The dropout rate was significantly greater in the moclobemide group. Both drugs induced an improvement in depressive and anxious symptomatology, with moclobemide showing a faster onset. Furthermore, moclobemide showed an enhancing effect on cognition, which was not shown by imipramine. Such results indicate that moclobemide could prove to be the drug of choice in geriatric depression, given that cognitive effects are prominent in the aged.
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PMID:Effects of moclobemide on depressive symptoms and cognitive performance in a geriatric population: a controlled comparative study versus imipramine. 795 85

Moclobemide is the first of a new generation of reversible inhibitors of monoamine oxidase-A (RIMA) with no clinically relevant potentiation of the hypertensive actions of dietary tyramine. The present study was conducted to compare the efficacy and safety of moclobemide with an established irreversible monoamine oxidase inhibitor, tranylcypromine, in depressed patients. Patients were randomized to receive moclobemide (81 patients) or tranylcypromine (79 patients) at individually titrated doses (100-300 mg/day of moclobemide and 10-30 mg/day of tranylcypromine) under double-blind conditions for at least four weeks, in a multicenter trial. Antidepressant efficacy was assessed using items 1-17 of the Hamilton depression rating scale (HAMD-17), the von Zerssen 'Befindlichkeits' scales, a visual analog scale and the clinicians' global impression. Both treatments resulted in significant amelioration of depression as determined by all rating instruments. HAMD-17 scores were reduced by 63% and 58% with moclobemide and tranylcypromine respectively, although the difference between the groups was not significant. The other rating instruments yielded similar results, apart from the clinician's assessment of efficacy at day 28. In this assessment, efficacy was rated as very good/good in 78% of moclobemide treated patients and in 88% of the tranylcypromine treated patients; however, only patients who had not dropped out of the trial were included in this assessment. The tolerability of both drugs was good, although moclobemide appeared to possess a small advantage in this regard since only one patient in this group was prematurely withdrawn from the trial due to inadequate tolerability/adverse events, compared with nine withdrawals in the tranylcypromine group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Double-blind comparison of moclobemide and tranylcypromine in depression. 812 28

The reversible monoamine oxidase-A (MAO-A) inhibitors were developed by researchers in response to safety concerns about the old irreversible MAO inhibitors. Scientists devised this new class of MAO-A inhibitors with the hope that selectivity for the MAO-A receptor and reversibility of the inhibition would result in efficacy in depression with improved safety. Moclobemide is the first reversible MAO-A inhibitor to be widely marketed and is currently approved for marketing in approximately 50 countries. In determining the safety profile of a drug, the following strategy is generally employed by a manufacturer: (a) comparison of the drug to placebo in clinical trials to identify the more commonly occurring adverse reactions; (b) comparison of the drug to other known drugs in clinical trials to determine relative frequencies of adverse reactions; (c) examination of reports from practitioners, the so-called spontaneously reported adverse event reports to confirm that what is seen under the experimental conditions of clinical trials is also seen in "real life" and to generate hypotheses about rare adverse reactions to the drug; (d) identification of further adverse reactions from overdose reports; and (e) the conduct of postmarketing studies to further determine drug-drug interactions. Such a strategy was employed by the manufacturer for moclobemide, and this article reviews the results of data accumulated concerning moclobemide safety.
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PMID:Safety of moclobemide in clinical use. 831 99

Moclobemide and fluoxetine were tested in a six-week trial involving 122 patients with major depressive illness. Patients initially received moclobemide, 150 mg three times daily, or fluoxetine 20 mg/day, but during weeks 3, 4, 5 and 6 the doses could be altered, giving a range of 300-600 mg/day for moclobemide or 20-40 mg/day for fluoxetine. No dietary restrictions were imposed on the patients. The trial was completed by 49 patients receiving moclobemide, and 43 patients receiving fluoxetine. The efficacies of these two agents, as determined on the Hamilton Depression Rating Scale and from Clinical Global Assessments, were found not to differ significantly. The frequencies of occurrence of adverse reactions were also similar, but sedation, nausea and vomiting were reported more frequently with fluoxetine, and insomnia was experienced with moclobemide. Tolerance of both drugs was judged to be high.
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PMID:A double-blind comparison of moclobemide and fluoxetine in the treatment of depressive disorders. 846 37

There has been a resurgence of interest in the use of monoamine oxidase (MAO) enzyme inhibitors for the treatment of depression. Unlike the first-generation MAO inhibitors, the current drugs are readily reversible in their action, resulting in far less concern about interactions with certain foods and drugs which could lead to serious pressor effects. Furthermore, the current drugs are far more selective in their actions as a result of the ability to affect either the MAO-A or the MAO-B isoenzyme. Moclobemide is an example of a reversible MAO-A inhibitor which has been extensively studied and whose pharmacokinetic, clinical pharmacological and toxicological profiles have been thoroughly defined. Moclobemide has a short disposition half-life and intermediate values for systemic clearance and volume of distribution; half-life increases somewhat with dose. The drug is completely metabolised by the liver. Moclobemide is rapidly and completely absorbed following oral administration in a variety of dosages and forms. The drug has a high intrinsic (apparent oral) clearance which results in a substantial hepatic first-pass effect and, while there is marked interindividual variation, differences within an individual are small. A time- and dose-dependence is observed with multiple oral administration: clearance decreases with administration during the first week and thereafter remains constant. The exact mechanism of this effect is not known, but it may reflect inhibition of elimination by metabolites (the kinetics may always be described as being first-order). Moclobemide disposition is not affected by renal disease, nor is there substantial alteration with advanced age. Liver disease causes a dramatic reduction in clearance; dosage must be adjusted for patients with liver disease. There is minimal transfer of the drug into breast milk, such that breast-feeding neonates are exposed to only a very small dose of the drug. Moclobemide administration results in a minimal interaction with exogenous amines (e.g. tyramine and pressor amine drugs); the so-called 'cheese effect' is therefore of little concern. As a result, the drug has an excellent tolerability profile both within the therapeutic dose range and in overdose (no deaths have been attributed to moclobemide intoxication per se). Cimetidine inhibits the elimination of moclobemide. Moclobemide appears to affect several isoenzymes of the cytochrome P450 (CYP) system (CYP2C19, CYP2D6 and CYP1A2). The adverse events profile of moclobemide indicates only mild and transient effects at a relatively low rate of occurrence.
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PMID:Clinical pharmacokinetics of the monoamine oxidase-A inhibitor moclobemide. 858 17

Unlike older monoamine oxidase inhibitors, which irreversibly and nonselectively bind monoamine oxidase (MAO), moclobemide is a reversible and selective inhibitor of the MAO-A isozyme. Moclobemide only weakly potentiates the pressor response induced by tyramine or other indirectly acting sympathomimetics; therefore, there is no need to avoid dietary tyramine or over-the-counter decongestants with moclobemide as there is with older MAO inhibitors. Recent clinical trials and meta-analyses have confirmed the efficacy of moclobemide in the treatment of depressive disorders. Moclobemide has been shown to have similar efficacy to tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs) and nonselective, irreversible MAO inhibitors. Long term follow-up studies of 6 to 12 months' duration have demonstrated that the antidepressant efficacy of moclobemide is maintained. Moclobemide, given alone or in combination with another antidepressant, has shown some efficacy in patients with refractory depression; however, comparative trials are required to confirm these findings. Data are also available to show clinical efficacy of moclobemide in the management of social phobia. Comparative studies have established that moclobemide is better tolerated at therapeutic dosages and has less toxicity in overdose than TCAs and nonselective, irreversible MAO inhibitors. Moclobemide lacks the anticholinergic, sedative and cardiovascular effects associated with many of the older antidepressants. Compared with SSRIs, moclobemide has a similar overall tolerability, although it tends to cause fewer gastrointestinal effects than the SSRIs and has not been reported to interfere with sexual function. In summary, recent data which confirm and extend its comparative therapeutic efficacy and low potential for adverse effects have established moclobemide as an effective treatment in depressive disorders. The drug is also effective in patients with a primary diagnosis of social phobia. Its lack of adverse anticholinergic, cardiovascular, cognitive and psychomotor effects makes moclobemide a particularly useful option in the elderly or patients with cardiac disease.
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PMID:Moclobemide. An update of its pharmacological properties and therapeutic use. 887 33

The pre-clinical development of moclobemide is an example of broad research combined with serendipity. Moclobemide was first hypothesized as being an antilipaemic or antibiotic, but the screenings were negative. The search for its antidepressant qualities, based on anticholinergic tests, also proved negative and moclobemide was then suspected of being an antipsychotic before its specific and reversible monoamine oxidase (MAO)-A inhibition qualities were detected. After the establishment of its lack of relevant interference with tyramine pressure response, clinical trials were launched in 1977. In the first stage, multiple, small open and double-blind studies were carried out. Two decisive, large, multicentre, double-blind studies were later performed in Latin America and Austria. Further trials have confirmed the broad antidepressant activity of reversible monoamine oxidase inhibitors (RIMA), which is not confined to any one subtype of depression and which show good tolerability and low toxicity. Since moclobemide has been available on the market, extensive meta-analyses of a large data set provided a series of methodological results: factor structure of the Hamilton Depression Scale (HAMD), optimal criteria of efficacy, predictors of response, onset of action for antidepressants and placebo.
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PMID:Moclobemide: a paradigm of research in clinical psychopharmacology. 892 3


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