Search results for "Monoamine oxidase"
showing 10 items of 47 documents
Inhibition of human monoamine oxidase A and B by flavonoids isolated from two Algerian medicinal plants
2017
Abstract Background Monoamine oxidases (MAOs) are outer mitochondrial membrane flavoenzymes. They catalyze the oxidative deamination of a variety of neurotransmitters. MAO-A and MAO-B may be considered as targets for inhibitors to treat neurodegenerative diseases and depression and for managing symptoms associated with Parkinson's and Alzheimer's diseases. Purpose The objective was to evaluate the inhibitory effect of Hypericum afrum and Cytisus villosus against MAO-A and B and to isolate the compounds responsible for the MAO-inhibitory activity. Methods The inhibitory effect of extracts and purified constituents of H. afrum and C. villosus were investigated in vitro using recombinant human…
Structure-Activity Relationship Analysis of 3-Phenylcoumarin-Based Monoamine Oxidase B Inhibitors
2018
Monoamine oxidase B (MAO-B) catalyzes deamination of monoamines such as neurotransmitters dopamine and norepinephrine. Accordingly, small-molecule MAO-B inhibitors potentially alleviate the symptoms of dopamine-linked neuropathologies such as depression or Parkinson's disease. Coumarin with a functionalized 3-phenyl ring system is a promising scaffold for building potent MAO-B inhibitors. Here, a vast set of 3-phenylcoumarin derivatives was designed using virtual combinatorial chemistry or rationally de novo and synthesized using microwave chemistry. The derivatives inhibited the MAO-B at 100 nM−1 μM. The IC50 value of the most potent derivative 1 was 56 nM. A docking-based structure-activi…
A Stage-Based Approach to Therapy in Parkinson’s Disease
2019
Parkinson’s disease (PD) is a neurodegenerative disorder that features progressive, disabling motor symptoms, such as bradykinesia, rigidity, and resting tremor. Nevertheless, some non-motor symptoms, including depression, REM sleep behavior disorder, and olfactive impairment, are even earlier features of PD. At later stages, apathy, impulse control disorder, neuropsychiatric disturbances, and cognitive impairment can present, and they often become a heavy burden for both patients and caregivers. Indeed, PD increasingly compromises activities of daily life, even though a high variability in clinical presentation can be observed among people affected. Nowadays, symptomatic drugs and non-phar…
Results of an Open Clinical Trial of Brofaromine (CGP 11 305 A), a Competitive, Selective, and Short-Acting Inhibitor of MAO-A in Major Endogenous De…
1987
In an open clinical trial the authors treated 18 hospitalized patients suffering from endogenous depression with brofaromine (CGP 11305A), a competitive, selective, and short-acting inhibitor of type A monoamine oxidase (MAO). Four patients were defined as good responders, as they had a final HAMD score of between 0 and 7 points. Four patients were judged as improved, with final HAMD scores of between 8 and 15 points, while the remaining eight patients failed to respond (final HAMD score greater than or equal to 16 points). The major observations were a beneficial influence on drive in most patients, while paranoid symptoms worsened markedly, rendering the substance contraindicated in psych…
Inhibition of dextromethorphan metabolism by moclobemide.
1998
This pilot study was conducted to evaluate the potential of the new antidepressant moclobemide to inhibit the cytochrome enzyme P4502D6 (CYP2D6) using the cough suppressant dextromethorphan as a substrate in four extensive metabolizers (EM) of debrisoquine. The subjects received seven oral doses of 20 mg dextromethorphan at 4-h intervals over 2 days (1 and 2) and subsequently moclobemide (300 mg b.i.d.) for 9 days. On days 10 and 11, they received seven doses of 20 mg dextromethorphan in addition to moclobemide. During monotreatment and combined treatment, blood was collected on days 2 and 11, respectively, for determination of dextromethorphan and its demethylated metabolites using automat…
The role of cytochrome P450 2D6 in the metabolism of moclobemide.
1996
The metabolic fate of moclobemide (Ro 11-1163), a new reversible and selective inhibitor of monoamine oxidase type A (MAO-A), has been assessed in a pilot study in 2 debrisoquine poor metabolizers (PM) and 4 extensive metabolizers (EM) after multiple oral dosings of moclobemide with and without co-medication of dextromethorphan. Absorption and disposition parameters were not different between PM and EM. Concurrent application of dextromethorphan, a selective substrate of CYP2D6, did not affect the pharmacokinetics of moclobemide. These results indicate that the cytochromal isoenzyme CYP2D6 does not play a major role in the metabolic degradation of moclobemide. Limited CYP2D6 activities beca…
TheMAOA T941G polymorphism and short-term treatment response to mirtazapine and paroxetine in major depression
2006
This study investigated the possible association of the MAOA T941G gene variant with differential antidepressant response to mirtazapine and/or paroxetine in 102 patients with major depression (DSM-IV criteria) participating in a randomized double-blind controlled clinical trial. Female mirtazapine-treated patients homozygous for the T-allele had a significantly faster and better treatment response than TG/GG-patients. In males, we failed to show an association between MAOA T941G gene variant and mirtazapine response. In the paroxetine-treated group, there were no significant differences in treatment response between MAOA T941G genotype groups. Time course of response and antidepressant eff…
Age-dependent decline of steady state dopamine storage capacity of human brain: an FDOPA PET study.
2010
Conventional indices of the utilization of FDOPA in living human brain have not consistently revealed important declines in dopamine function with normal aging. However, most methods of kinetic analysis have assumed irreversible trapping of decarboxylated FDOPA metabolites in brain, an assumption that is violated even in PET recordings of short duration. Therefore, we have developed methods for the calculation of steady-state storage of FDOPA together with its decarboxylated metabolites (V(d), mlg(-1)), based upon improved kinetic analysis of 120-min emission recordings. In a group of 28 normal male subjects, of age ranging from 23 to 73 years, the magnitude of V(d) in the striatum and in e…
Clinical responses to antidepressants among 1036 acutely depressed patients with bipolar or unipolar major affective disorders.
2012
Whether responses to antidepressants differ in bipolar and unipolar depression remains unresolved.We analyzed patient characteristics and outcomes of antidepressant treatment of 1036 depressed patients with bipolar-I or bipolar-II disorder, or unipolar major depression, using bivariate and multivariate methods and survival analysis, testing the hypothesis that responses would be superior in unipolar depression.Antidepressants were given to 84.8% (878/1036) of depressed patients: 58.9% of 93 bipolar-I, 80.1% of 117 bipolar-II, and 91.3% of 668 unipolar disorder cases. The 158 not given antidepressants had more manias/year, spent more months in mania and depression, and were far more likely t…
Effects of moclobemide on sexual performance and nocturnal erections in psychogenic erectile dysfunction
2001
Rationale and objectives: We tested the hypothesis that the selective reversible MAO-A inhibitor moclobemide has a specific therapeutic effect on erectile dysfunction independent of its antidepressive properties. Methods: In a double-blind placebo controlled study, 12 male outpatients suffering from psychogenic erectile dysfunction without any other psychiatric disorder were investigated. Based on comprehensive diagnosis before the beginning of the study, organic factors relevant for sexual function were excluded. The treatment period was 8 weeks. Half the patients received 450 mg moclobemide during the first week, and 600 mg afterwards; the others received placebo. Apart from assessment of…