Disease relevance of moclobemide

• Hypertension with moclobemide [1].
• Intrahepatic cholestasis associated with moclobemide leading to death [2].
• Mirtazapine is unable to precipitate serotonin toxicity in overdose or to cause serotonin toxicity when mixed with monoamine oxidase inhibitors, and moclobemide is unable to precipitate serotonin toxicity in overdose [3].
• It is likely that entacapone and moclobemide will be used concomitantly in the future in patients who have both Parkinson's disease and depression [4].
• Combined treatment with corticosteroids and moclobemide favors normalization of hypothalamo-pituitary-adrenal axis dysregulation in relapsing-remitting multiple sclerosis: a randomized, double blind trial [5].

Psychiatry related information on moclobemide

• OBJECTIVE: To assess the effectiveness of moclobemide on smoking cessation and abstinence in heavy, dependent smokers [6].
• Compared with placebo, all drugs induced significant subjective pain threshold increases (maximal increase: desipramine, +20%; fluvoxamine, +17%; moclobemide, +13%) [7].
• Biological parameters in major depression: effects of paroxetine, viloxazine, moclobemide, and electroconvulsive therapy. Relation to early clinical outcome [8].
• 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 [9].
• Moclobemide in social phobia [10].

High impact information on moclobemide

• Moclobemide treatment leads to a 64% to 79% MAO-A blockade across brain regions, a result that supports the specificity of [(11)C]-harmine binding to MAO-A [11].
• Effect of omeprazole on the pharmacokinetics of moclobemide according to the genetic polymorphism of CYP2C19 [12].
• We conducted a double blind, placebo-controlled trial to evaluate the neuroendocrine effect of cotreatment with the antidepressant moclobemide as an adjunct to oral corticosteroids in MS [5].
• It was therefore considered to be important to investigate the tolerability of combined COMT and MAO-A inhibition with entacapone and moclobemide [4].
• A combined mephenytoin, sparteine, and caffeine test performed before, during, and after multiple dosing of moclobemide showed changes in the metabolic indexes compatible with a reversible inhibition of oxidation by way of the corresponding CYP enzymes--CYP2C19, CYP2D6, and CYP1A2--during moclobemide treatment [13].

Chemical compound and disease context of moclobemide

• Some other controlled studies have found moclobemide and brofaromine, another reversible monoamine oxidase inhibitor, efficacious in social phobia [14].
• Pharmacotherapy of social phobia. A controlled study with moclobemide and phenelzine [15].
• We have given moclobemide, a selective, reversible inhibitor of MAO-A, to nondepressed patients with Parkinson's disease receiving standard levodopa/peripheral decarboxylase inhibitor or levodopa with dopaminergic agonist (bromocriptine, pergolide) [16].
• The most frequent complaints in the moclobemide-treated group were hot flushes, dry mouth, constipation and headache, while an increase in anxiety was associated with toloxatone usage [17].
• CONCLUSIONS: The potentiation of tyramine-evoked mydriasis by moclobemide is likely to reflect the inhibition of MAO-A activity in the iris, consistent with the activity of this enzyme in sympathetic nerve terminals [18].

Biological context of moclobemide

• OBJECTIVE: To assess the tolerability, safety, pharmacokinetics, and pharmacodynamics of combined treatment with fluoxetine and moclobemide in healthy subjects [19].
• The duration of the systolic blood pressure increase was longer with tranylcypromine (126 minutes) than with moclobemide (69 minutes) (p less than 0.01) [20].
• Disposition kinetics of moclobemide, a monoamine oxidase-A enzyme inhibitor: single and multiple dosing in normal subjects [21].
• Moclobemide versus clomipramine in depressed patients in general practice. A randomized, double-blind, parallel, multicenter study [22].
• According to this antimode, control subjects exhibited identical phenotypes and genotypes, whereas patients under paroxetine, moclobemide or metoprolol who had been genotyped as extensive metabolizers were poor metabolizer phenotypes [23].

Anatomical context of moclobemide

• Moclobemide upregulated Bcl-2 expression and induced neural stem cell differentiation into serotoninergic neuron via extracellular-regulated kinase pathway [24].
• In this issue, Chiou et al. have elegantly demonstrated that cells isolated from the rat hippocampus, and treated with the antidepressant moclobemide, may be differentiated in vitro into neural cells exhibiting features to those of serotoninergic neurons [25].
• Brain mapping after moclobemide treatment showed an overall reduction in frontal lobe delta activity [26].
• Enhanced morphine-induced behavioural effects and dopamine release in the nucleus accumbens in a transgenic mouse model of impaired glucocorticoid (type II) receptor function: influence of long-term treatment with the antidepressant moclobemide [27].
• The MAOI activity of SR 95191 was examined in the rat brain, liver and duodenum and compared to that of clorgyline, harmaline, l-deprenyl, moclobemide and cimoxatone [28].

Associations of moclobemide with other chemical compounds

• Cimetidine alters the disposition kinetics of the monoamine oxidase-A inhibitor moclobemide [29].
• In this article, we describe a series of meta-analyses of studies of the two most widely researched RIMAs, moclobemide (MOC; Aurorex) and brofaromine (BRO) [30].
• Almotriptan clearance was reduced, to a modest degree, by moclobemide and verapamil, which was consistent with the contribution of monoamine oxidase-A and CYP3A4 to the metabolic clearance of almotriptan [31].
• The purpose of this report is to evaluate disturbances in sexual drive/desire and arousal/orgasm in 107 patients who met criteria for major depressive disorder and received treatment with either moclobemide, paroxetine, sertraline, or venlafaxine [32].
• Coadministration with a MAO-A inhibitor, moclobemide, leads to a significant increase in sumatriptan plasma concentrations and is contraindicated [33].

Gene context of moclobemide

• Moclobemide, an MAO-A inhibitor, is already in clinical use as an antidepressant [4].
• Moclobemide thus partially undergoes oxidative metabolism by way of the polymorphic CYP2C19 [13].
• The authors describe the use of moclobemide in a 27-year-old patient with comorbid opiate addiction and ADHD (residual type) [34].
• Correlations were observed between moclobemide N-oxidation and specific cytochromre P450 (CYP) activities at both moclobemide concentrations (0.1 mM moclobemide, CYP2C19 0.66, p < 0.05; 4 mM moclobemide, CYP2E1 rs = 0.56, p < 0.05) [35].
• Although it acts as an inhibitor of CYP1A2, CYP2C19, and CYP2D6, relatively few clinically important drug interactions involving moclobemide have been reported [36].

Analytical, diagnostic and therapeutic context of moclobemide

• The dexamethasone suppression test (DST) was conducted in 95 elderly DSM-III-R depressed patients randomized for treatment with moclobemide (MOC; 400 mg daily), nortriptyline (NT; 75 mg daily), or placebo (PBO) in a 7-week double-blind multicenter study [37].
• Positron emission tomography studies were performed in healthy volunteers at placebo conditions and after treatment with clinical doses of moclobemide [11].
• Moclobemide and tricyclic antidepressants in severe depression: meta-analysis and prospective studies [38].
• In clinical trials, moclobemide appeared only slightly less well tolerated than placebo [39].
• Moclobemide is rapidly and completely absorbed following oral administration in a variety of dosages and forms [40].

References