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

Depressed outpatients (n = 51) resistant to treatment with maprotiline were treated in a blind, randomized, single-centre study, for 6 weeks with either the reversible and selective monoamine oxidase A-inhibitor (MAO-A-I), brofaromine or lithium addition to maprotiline. The Hamilton Rating Scale for Depression was scored by an independent rater before and after the 6 week treatment period. No significant differences in efficacy were found between the two treatment regimes. In the patients who completed the trial, brofaromine was well tolerated with the exception of insomnia. Anticholinergic effects as well as thyroid dysfunctions (17 out of 20) were more frequent in the maprotiline/lithium group.
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PMID:Brofaromine versus lithium addition to maprotiline. A double-blind study in maprotiline refractory depressed outpatients. 800 48

The first generation of monoamine oxidase (MAO) inhibitors fell into disuse because of poor efficacy in major depression with melancholia and/or endogenous depression, and because of poor tolerability (drug interactions and the 'cheese' effect). New MAO inhibitors, reversible inhibitors of MAO-A (RIMAs), are able to induce a reversible and specific inhibition of MAO-A. Consequently, the inhibition of MAO is quicker and the dose-response relationship improved, such that dosage adjustment is easier. Also, no carry-over effect once treatment is terminated is observed. The frequency and severity of drug interactions with RIMAs is reduced, although coadministration with pethidine (meperidine) or dextromethorphan should still be avoided. No specific subgroup of patients with depression has shown a better or worse response to RIMAs. The presence of melancholia in major depression, or the existence of endogenous depression, are not predictive of reduced efficacy compared with tricyclic antidepressant (TCA) reference compounds. Dysthymic patients have shown a good response to both RIMAs and TCAs independent of the co-existence of a major depressive episode. Older MAO inhibitors are more effective than TCAs in the treatment of atypical depression, and further studies are needed to confirm if this is true for RIMAs. Long term studies to evaluate the effects of RIMAs on disease recurrence are also required. RIMAs are better tolerated than older MAO inhibitors, including use in subgroups particularly at risk of adverse effects such as the elderly. Overall, RIMAs appear to represent therapeutic progress in the treatment of depression in terms of both efficacy and tolerability.
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PMID:Risk-benefit assessment of newer versus older monoamine oxidase (MAO) inhibitors. 801 1

The reversible, selective monoamine oxidase A inhibitor moclobemide (450 mg daily) was compared with imipramine (150 mg daily) and placebo in a multicentre, controlled clinical trial lasting 6 weeks. Two hundred and forty-nine patients participated, with a major depressive episode according to DSM-III criteria, and whose initial Hamilton Depression Scale rating (HDRS) was at least 17. Clinical improvement, as determined by HDRS, was similar in the three treatment groups: 53% of the evaluable patients in the moclobemide group responded (i.e. a 50% reduction in HDRS), compared with 50% on imipramine and 51% on placebo. Tolerability was least on imipramine, largely due to the high frequency of anticholinergic side effects; moclobemide showed no difference from placebo in this respect.
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PMID:A multicentre comparative trial of moclobemide, imipramine and placebo in major depressive disorder. UK Moclobemide Study Group. 805 92

In the course of investigating a large number of non-demented subjects, a 68 year old female dying of coronary artery disease was found to have Pick bodies in her grossly normal brain. Although only mild subcortical gliosis and no neuron loss were observed. Pick bodies were found throughout the brain and occasional balloon cells were noted. Pick bodies and numerous neurons were also ALZ-50 and Tau-1 immunoreactive. Retrospective studies indicated a lack of overt intellectual decline or depression in this individual. Frontal, temporal and occipital poles, amygdala, hypothalamus and nucleus basalis of Meynert (nbM) were analyzed for ChAT, AChE and MAO-A and -B enzymatic activities and for the binding of 5HT and imipramine. Cholinergic decreases were found only in subcortical structures. Serotonin binding decreases were widespread, excluding the nbM. Altered MAO-B activity was regionally variable, and no differences in MAO-A activity or imipramine binding were observed. Few differences in neurochemical alterations were observed in the current non-demented subject with abundant Pick bodies compared to previous studies of demented Pick's patients. This case strongly suggests that chemical dysfunction and neuropathological features of Pick's disease occur in advance of overt clinical manifestations of the disorder.
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PMID:Neurochemical and histopathologic alterations characteristic of Pick's disease in a non-demented individual. 830 18

The clinical efficacy of the monoamine oxidase A inhibitor moclobemide and its effect on the dexamethasone suppression test (DST) and plasma and urine methoxyhydroxyphenylglycol (MHPG) were investigated in 26 depressed patients during a 4-week clinical trial. Fourteen patients (54%) responded favourably to the treatment (50% or more reduction of the Hamilton Rating Scale for Depression score). All (8) patients with an abnormal DST responded to treatment; 11 of 16 patients with a normal DST did not respond. Patients with low pretreatment MHPG excretion, according to the median value, were more frequently treatment responders. Plasma and urine MHPG were significantly decreased by treatment. The results indicate that low excretion of MHPG and cortisol nonsuppression may be considered as predictors of favourable clinical response to moclobemide treatment.
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PMID:Clinical, endocrine and neurochemical effects of moclobemide in depressed patients. 848 51

Antidepressant drugs are among the most commonly encountered causes of self-poisoning. These drugs include tricyclics, tetracyclics, bicyclics and monocyclics, as well as monoamine oxidase (MAO) inhibitors and selective serotonin reuptake inhibitors (SSRIs). Of these, the tricyclic antidepressants (TCAs) are generally more toxic in overdose, with major toxicity usually manifesting within the first 6 hours after overdose. Various studies indicate that patients at risk of toxicity from TCA overdose may be identified by neurological, cardiovascular and electrocardiography status, together with a quantitative estimate of the plasma drug concentration. While there are various methods available for such chemical estimations, the most satisfactory appears to be fluorescence polarisation immunoassay which gives rapid quantitative results for a variety of TCAs. The selective MAO-A inhibitor antidepressants and the SSRIs are relatively nontoxic when taken alone. However, overdoses of combinations of MAO inhibitors and either SSRIs or TCAs with serotonin reuptake blocking activity may result in a serotonin syndrome with a severe or fatal outcome. Features of this syndrome include hyperpyrexia, disseminated intravascular coagulation, convulsions, coma and muscle rigidity, which may not develop until 6 to 12 hours after overdose. While quantitative chemical identification of these drugs following overdose is helpful in confirming the diagnosis, it is not mandatory. The increasing use of MAO-A inhibitors and SSRIs in the treatment of depression suggests that careful clinical observation is required when combination overdoses are suspected.
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PMID:Antidepressant toxicity and the need for identification and concentration monitoring in overdose. 852 78

Psychopharmacotherapy of the elderly must take into account the effects of age-related changes in the structure and function of the brain and various organs. In general, older people are more sensitive than young people to both the therapeutic and toxic effects of psychotropic medications, necessitating lower doses and longer dosage intervals. This holds true for the treatment of 5 major types of psychiatric illness (depression, bipolar disorder, anxiety, psychotic disorders and dementia). The tricyclic antidepressants, although efficacious, inexpensive, and backed by 30 years of experience, are less well tolerated by the elderly than are newer antidepressants such as the selective serotonin uptake inhibitors. Problems with monoamine oxidase (MAO) inhibitors, including orthostatic hypotension and restrictions in diet and other medication use, have been overcome by the advent of reversible selective inhibitors of MAO-A, but the efficacy of these in the elderly has yet to be proven in clinical trials. Lithium remains the mainstay for the treatment of bipolar disorder. However, careful dosing and monitoring of plasma lithium concentrations are required in the elderly due to changes in pharmacokinetics and pharmacodynamics which make older patients very sensitive to the toxic effects of this medication. Similarly, age-related changes in the pharmacokinetics and pharmacodynamics of the benzodiazepines, the most frequently prescribed medications for anxiety in the elderly, result in recommendations for lower doses and preferential use of those agents metabolised by conjugation (e.g. oxazepam). Buspirone, a partial serotonin 5-HT1A-agonist which is better tolerated than benzodiazepines in the elderly, may be used as an alternative. The elderly are extremely sensitive to extrapyramidal adverse effects which the typical antipsychotics (neuroleptics) exhibit to varying extents. The selection of a suitable agent for the treatment of a psychotic disorder should be based upon the adverse effect profile of the drug and the specific symptoms and situation of the patient. The newer atypical antipsychotics, clozapine and risperidone, have yet to be well-studied in the elderly. Dementia, exemplified by Alzheimer's disease, is almost exclusively an illness of the elderly. Only one medication, tacrine, has been approved for its treatment, based on extensive basic research and positive results of several clinical trials. Its long-term benefits have yet to be determined and it has several adverse effects, including a tendency to increase liver enzymes to the extent that the medication has to be discontinued.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Recent advances in geriatric psychopharmacology. 853 49

There is a strong association between depression and smoking. Because monoamine oxidase (MAO) inhibition leads to antidepressant effect and in vitro studies have shown that cigarette smoke inhibits MAO activity, it is conceivable that smoking may have an antidepressant effect, if smokers have reduced MAO activity. Therefore, we assessed platelet MAO-B activity and plasma concentration of catecholamine metabolites reflecting MAO-A activity in heavy dependent smokers and nonsmokers matched for sociodemographic characteristics. Platelet MAO-B activity, plasma 3,4-dihydroxyphenylglycol, plasma 3,4-dihydroxyphenylacetic acid, and plasma 3,4-dihydroxyphenylalanine concentrations were significantly lower in smokers than in nonsmokers, whereas plasma norepinephrine did not differ. Significantly more smokers reported previous history of depression, manic episode, panic attack, agoraphobia, and simple phobia. Smokers had higher scores (p < 0.001) on the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Scales. It is concluded that the activities of both forms of the MAO are reduced in heavy dependent smokers.
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PMID:Monoamine oxidase A and B activities in heavy smokers. 858 Feb 30

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


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