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)

The purpose of the work was to specify the possibilities of the use of the enzymes of mediator metabolism: monoamine oxidase (MAO) of platelets, amine oxidase (AO) of serum and acetyl cholinesterase (ACE) of red blood cells to estimate the structure of depressions and to predict their therapeutic dynamics. 32 patients in the depressive phase of MDP were examined. There were 28 women and 4 men aged 22 to 50 years. The monopolar type was recorded in 28 patients, the bipolar one in 4 (all women). The total disease duration amounts to 0.5-17 years; depression may last from 2 months to 4 years. Depending on the type of the dominant affect the patients were distributed into 2 groups (10 persons had melancholic and 22 anxious depression). It has been shown that activity of platelet MAO and serum AO was significantly higher in anxious than in melancholic depression. An interrelationship was established between activity of these enzymes before treatment and prognosis of the treatment with tricyclic antidepressants. Activation of the enzymes during therapy was parallelled by positive clinical changes. Activity of platelet MAO turned out most significant in terms of prognosis. The data obtained are analyzed from the standpoint of regarding depression as a stressful condition, with the participation of the neurohormonal axis: the hypothalamus, pituitary, and adrenal cortex.
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PMID:[Significance of various enzymes of mediator metabolism for evaluation of depression and therapeutic prognosis]. 131 64

Whilst tricyclic antidepressants are efficacious in all depressive syndromes, classical MAO-inhibitors differ substantially from them in their action. They are considered less effective in general and not very effective in endogenous depression, but recommended for the treatment of 'atypical' depression. A new class of RIMA (Reversible Inhibitors of MAO-A) represented by moclobemide requires a change in clinical thinking on antidepressants. Moclobemide shows the same efficacy in depression as tricyclics: its effects are similar in unipolar and bipolar affective disorders, and in patients with major depressive episode superimposed on dysthymia (double depression). As with classical antidepressants, the response rate tends to be lower, but is still present in psychotic depression. Agitated depressives do not respond less well than non-agitated patients to moclobemide. Patients meeting DSM-III-R criteria for major depression with melancholia tend to respond better than non-melancholics, but this may be associated with the significantly higher baseline severity observed in melancholics. A slightly higher response rate in patients without concomitant benzodiazepine treatment, compared to those with benzodiazepine comedication, may also be related to baseline differences in the severity of depression. Elderly depressives respond less well than younger patients to classical antidepressants, but with moclobemide, elderly patients do as well as younger ones.
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PMID:Efficacy of moclobemide in different patient groups: a meta-analysis of studies. 134 58

The peculiar tyramine uptake inhibitory effect of (-)deprenyl prompted structure-activity relationship studies aiming to develop new spectrum central nervous system stimulants which are devoid of MAO inhibitory potency and operate de facto as indirectly acting, nonreleasing sympathomimetics. Of the derivatives synthesized for this purpose, 1-phenyl-2-propylaminopentane (PPAP) was selected as the reference substance and its pharmacological spectrum is presented. PPAP is taken up by the catecholamine axon terminal membrane and the vesicular membrane but it is devoid of catecholamine-releasing property. As a result, PPAP is, by interference, a potent inhibitor of the uptake of indirectly acting sympathomimetic releasers and of the catecholamine transmitters. This was proved, on the one hand, by measuring the uptake of [14C]PPAP into the catecholaminergic axon terminals and the inhibition of the uptake of [3H]noradrenaline and [3H]dopamine by PPAP in the rat brain, and, on the other hand, on the pulmonary artery strip of the rabbit and, in vivo, using the rat nictitating membrane as a detector. PPAP increases motility at 2 mg/kg and, in contrast to amphetamine, inhibits it at very high doses (50 mg/kg) only. A two-sided antagonism in the motility-increasing effect between PPAP and amphetamine and, more pronounced, between PPAP and mazindol was detected. PPAP is substantially less effective in inducing stereotyped behavior than either amphetamine or methamphetamine. PPAP facilitates learning and retention, is highly potent in antagonizing the tetrabenazine-induced depression in behavioral tests and is very effective in the forced swimming test. Whereas amphetamines facilitate performance in a very narrow range of low doses, which turns, at a modest elevation of the dose, into the opposite effect, PPAP improves performance within a reasonably broad dose range. Based on the peculiar pharmacological profile of PPAP, its potential usefulness in depression, in Alzheimer's disease and in attention-deficit-hyperkinetic disorder seems to be plausible.
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PMID:The pharmacology of 1-phenyl-2-propylamino-pentane (PPAP), a deprenyl-derived new spectrum psychostimulant. 135 24

Optimal treatment of mood disorders and prevention of suicide requires biological and psychosocial methods, therapeutic alliance and psycho-education. In moderate unipolar depression an antidepressant may be sufficient, if necessary potentiated by another antidepressant or triiodothyronine. In moderate bipolar depression lithium or carbamazepine are preferred. In severe unipolar and bipolar depression the combination of an antidepressant and lithium (or carbamazepine) or electroconvulsive therapy (ECT) is indicated, in psychotic depression neuroleptics, too. Non-selective monoamine oxidase inhibitors (MAOIs) are the most potent antidepressants. Moderate acute mania and mixed state may respond to lithium, carbamazepine or valproate only. In severe cases a neuroleptic and lithium are combined, or these drugs may be combined with carbamazepine or valproate. Electroconvulsive therapy is preferable in acute mixed states with marked confusion or depression. In chronic mixed state and rapid cycling, withdrawal of antidepressants and neuroleptics should be tried. Most patients will need a combination of lithium and carbamazepine or valproate. Added to these drugs, antidepressants are less risky. Adding thyroxin may stabilize rapid cycling. The combination of lithium and an antidepressant is the most potent prophylaxis in unipolar disorder and bipolar disorder dominated by depression.
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PMID:[Affective disorders. Drug treatment and electroconvulsive therapy]. 135 73

Moclobemide is a reversible and selective inhibitor of the enzyme monoamine oxidase (MAO) subtype A with a broad spectrum of antidepressant activity. Controlled clinical studies suggest that the short term clinical efficacy of moclobemide is significantly superior to that of placebo, and comparable to that of the tricyclic antidepressants clomipramine, amitriptyline, imipramine and desipramine, the irreversible MAO inhibitor tranylcypromine and the second-generation antidepressants maprotiline, mianserin and fluvoxamine in the treatment of major depressive illness. Moclobemide appears to be equally effective in endogenous and nonendogenous depression, producing marked amelioration of clinical features of psychomotor retardation and depressed mood. Moclobemide is well tolerated, being largely devoid of the anticholinergic adverse effects, symptomatic postural hypotension and weight gain variously associated with the tricyclic antidepressants and irreversible MAO inhibitors, and appears considerably safer on overdosage than the tricyclic and second generation antidepressants. Moreover, moclobemide offers the advantage over the older, irreversible MAO inhibitors of causing only minimal potentiation of the pressor response to dietary tyramine (the so-called 'cheese effect'). Consequently, the risk of potentially fatal hypertensive crisis, a major deterrent to the wider acceptance of these earlier compounds, is substantially reduced with moclobemide, and the need for dietary precautions is minimised. With its efficacy against endogenous and nonendogenous depression, relatively rapid onset of antidepressant activity, and absence of carry-over effects on treatment withdrawal, moclobemide is likely to make an important contribution to the treatment of major depressive illness. Its favourable tolerability profile, safety on overdosage and beneficial effect on age-related cognitive impairment may be of particular value in the elderly and those with concurrent physical illness.
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PMID:Moclobemide. A review of its pharmacological properties and therapeutic use in depressive illness. 137 19

Selective serotonin reuptake inhibitors (SSRIs) are a recently developed class of drugs with significantly greater antidepressant efficacy than placebo. Generally, in double-blind comparative trials, all SSRIs demonstrated antidepressant efficacy similar to that of the 'standard' tricyclic antidepressants amitriptyline and imipramine; a meta-analysis of controlled trials found the efficacy of the SSRIs to be equivalent to that of the 2 tricyclics. Nevertheless, because of small patient numbers included in most studies that compare SSRIs with other antidepressants, no definitive statements about relative efficacy can be made. In these studies it is simply possible to state that no statistically significant differences were identified between SSRIs and the comparative antidepressants. Importantly, differences in clinical characteristics exist between the SSRIs-differences in elimination half-life (t1/2 beta) between fluoxetine and/or its metabolite (total t1/2 beta = 330 hours) and other SSRIs (t1/2 beta range = 15 to 30 hours), for example. This has implications in terms of potential drug interactions and must be considered when patients have to be switched to treatment with monoamine oxidase inhibitors. Studies with fluvoxamine have been conducted in both in- and outpatients, whereas trials with other SSRIs have been confined largely to outpatient populations. Fluvoxamine has been associated with a high incidence of nausea (37%), although this may have resulted from high initial dosages (rather than upward dose titration protocols) used in early trials. Of further interest, fluoxetine doses of 20mg may be sufficient to produce a satisfactory antidepressant response, and this SSRI may be particularly useful in patients with chronic retarded depression. More clinical data are required before the efficacy of sertraline and citalopram relative to standard antidepressants can be clearly defined. Preliminary data indicate that SSRIs are effective in the treatment of panic disorder, obsessive-compulsive disorder (OCD), eating (e.g. anorexia and bulimia) and personality disorders (e.g. anger, impulsiveness) and substance abuse (e.g. alcoholism); early results with fluvoxamine in the treatment of panic disorder and OCD, and with fluoxetine in the treatment of bulimia, personality disorders and alcohol abuse, have been encouraging. SSRIs have a more favourable tolerability profile than tricyclic antidepressants and, unlike the tricyclics, are not associated with anticholinergic adverse effects, sedation, cardiotoxicity or weight gain. SSRIs are associated with a relatively high incidence of nausea, particularly if high doses are used at the start of treatment. However, the incidence of nausea appears to decrease as treatment is continued.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Comparative efficacy of antidepressants. 137 69

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

We examined the influence of toloxatone, a new reversible monoamine oxidase-A inhibitor used in the treatment of depression, on tyramine-induced pressor effect in healthy volunteers. The maximum increase in systolic blood pressure produced by four single oral doses of tyramine administered during a meal and ranging from 100 mg to 800 mg was compared during repeated (3 to 5 days) administration of placebo, 200 mg toloxatone three times a day and 400 mg toloxatone three times a day in a single-blind, three-period crossover study. Toloxatone by itself had no significant influence on blood pressure. During administration of toloxatone, no significant increase in tyramine-induced increase in systolic blood pressure was observed for tyramine doses of 200 mg or less that are consistently higher than those associated with normal food intake. However, toloxatone increased the tyramine-induced increase in blood pressure after 400 mg tyramine (400 mg toloxatone three times a day) and 800 mg tyramine (200 mg toloxatone three times a day and 400 mg toloxatone three times a day). This pharmacodynamic interaction could be explained by an increase in tyramine systemic bioavailability in the presence of toloxatone. It is concluded that interaction between tyramine in meals and toloxatone is unlikely to occur in patients after long-term administration of the drug at therapeutic dosages.
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PMID:Pharmacokinetic and pharmacodynamic interaction between toloxatone, a new reversible monoamine oxidase-A inhibitor, and oral tyramine in healthy subjects. 142 10

Because of the limitations in efficacy and safety of the older tricyclic antidepressants (TCA) and monoamine oxidase inhibitors (MAOI) a number of new approaches have been made in recent years to the treatment of depression to obtain more effective, more rapidly acting, better tolerated and safer drugs. One tactic has been to develop compounds with greater neuropharmacological selectivity in inhibiting the neuronal reuptake of 5-HT. Most of these are as effective as TCA but with fewer side-effects and greater safety. Another development has been 'reversible' MAOI which reduce the risk of interaction with tyramine-containing foods. For resistant depression the addition of lithium (and/or tryptophan) may be effective, possibly through promoting 5-HT neurotransmission. Continuous treatment with a selective 5-HT reuptake inhibitor can reduce the relapse rate in patients with recurrent depression. Unfortunately, these new approaches, despite their advantages in terms of side-effects and safety, have thus far not proved to be more effective or faster acting than the standard TCA. That remains a challenge for the future.
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PMID:New aspects in the treatment of depression. 143 Oct 20

Psychostimulants, including ritalin (methylphenidate), were used as antidepressives in the '50s but were then replaced by tricyclics and MAO inhibitors. Treatment of depression with psychostimulants is still controversial. Several anecdotal reports in the past decade approved the use of tricyclic antidepressants (TCA) together with methylphenidate in apathetic and withdrawal states in medically ill and in elderly patients. Ritalin elevates mood by releasing catecholamines and blocking their re-uptake, and also increases serum TCA levels. 5 men and 5 women between the ages of 65 and 79 were diagnosed as suffering from major depressive disorders, either single or recurrent, based on the Revised Diagnostic and Statistical Manual for Mental Disorders (DSM-III-R). They had been treated with TCA for up to several months with no response. Following addition of methylphenidate, 5-15 mg/d for 2 weeks, 4 men and 3 women improved rapidly, 2 of them within 24 hours.
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PMID:[Combined tricyclic antidepressants and ritalin in elderly depressives]. 145 98


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