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)

A series of studies on the pharmacokinetic and pharmacodynamic properties of some tricyclic antidepressants is reviewed. During treatment with the same oral dose of these drugs, patients develop widely differing plasma levels. The importance of this variability for the clinical effects has been studied in detail for the monomethylated compound, nortriptyline. There is an association between side-effects and high plasma levels of this drug. In endogenously depressed patients, the relationship between plasma level and effect appears to be curvilinear. The tricyclic antidepressants differ in their capacity to inhibit transmitter uptake into noradrenaline- and serotonin neurons respectively. Nortriptyline is a preferential noradrenaline uptake inhibitor, while the dimethylated compound, chlorimipramine also has a profound influence on serotonin neurons. These differential effects are also reflected in changes in the levels of the transmitter metabolites in cerebrospinal fluid (CSF). The CSF studies have also supported the hypothesis of a biochemical heterogeneity of the depressive syndrome. The levels of the serotonin metabolite, 5-HIAA were bimodally distributed in CSF. In patients with a low level of 5-HIAA there was a significant correlation between the CSF metabolite level and the severity of the depression, and these patients also appeared to be more suicide-prone than those with higher 5-HIAA levels. These patients seemed to be less amenable to treatment with nortriptyline. The effect of chlorimipramine treatment in this subgroup of depressives is presently being explored.
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PMID:Treatment of depression with tricyclic drugs--pharmacokinetic and pharmacodynamic aspects. 1 May 83

There is a suggestive evidence for a relationship between central 5-HT and the occurrence of certain types of depressions. This evidence is derived from three sources: postmortem studies; measurement of CSF 5-HIAA; accumulation of CSF 5-HIAA after transport blockade by probenecid. Disturbances of central 5-HT metabolism are not typical for any depression but for certain types of vital (endogenous) depression. This implies that the group of vital depression, though tending towards homogeneity in terms of symptomatology, is heterogenous in biochemical terms and comprises patients with and without disorders in central 5-HT metabolism. It is plausible that disorders of the 5-HT metabolism play a role in the pathogenesis of depression, instead of resulting from them. This statement is based on the following findings: (i) 5-HTP can abolish or alleviate the depressive syndrome or some of its elements. (ii) This 5-HTP effect can be potentiated by clomipramine (Anafranil), a relative selective inhibitor of 5-HT reuptake. (iii) There exists a negative correlation between 5-HT turnover in the CNS and the therapeutic effect of clomipramine. The alleged distrurbances in central 5-HT are more likely to be predisposing than of direct causative significance. This assumption is based on two observations: (i) In more that 50% of cases, the 5-HT turnover remains low after clinical recovery, the patient being drug-free. (ii) There is suggestive evidence that abolition of the 5-HT deficit (by means of 5-HTP) exerts a prophylactic effect in uni-and bipolar depression.
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PMID:The Harold E. Himwich Memorial Lecture. Significance of biochemical parameters in the diagnosis, treatment, and prevention of depressive disorders. 30 32

16 patients with organic depression were treated with low doses of trazodone (100 mg/day) by i.v. infusion. This drug was shown to have a marked antidepressant and anxiolytic action and did not produce any significant side-effects. The authors suggest that on the basis of the diminished 24-hour urinary excretion of 5-HIAA, trazodone seems to have an antiserotonin action at low doses.
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PMID:Trazodone by intravenous infusion in depressions secondary to organic disease. 33 Apr 41

In 30 patients suffering from vital depression (the syndrome of endogenous depression) a negative correlation was found between the pre-therapeutic post-probenecid CSF 5-HIAA response and the therapeutic response to clomipramine (Anafranil). Clomipramine is a tricyclic antidepressant with a strong potentiating effect on central 5-HT. The following conclusion was drawn: if the cenral 5-HT turnover is diminished in depressions, then correction of this biochemical disturbance leads to alleviation of depressive symptoms. This finding is considered to support the concept of '5-HT-deficient depression'. Five of the 8 clomipramine-resistant patients showed a favourable response to nortriptyline, a NA-potentiating anti-depressant. The pre-therapeutic CSF MHPG concentration in these patients was not related to the therapeutic efficacy of nortriptyline. So, the assumption that these patients have been NA-deficient was not confirmed. However, renal MHPG excretion was not measured and possibly this variable correlates better with cerebral NA metabilism than MHPG in lumbar CSF which is of mainly spinal origin.
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PMID:New evidence of serotonin-deficient depressions. 89 99

Cerebrospinal fluid 5-hydroxyindoleacetic acid levels were determined in 31 women with unipolar involutional depression using the probenecid technique. Values were found to be lower in depression as compared to controls, but they did not correlate with the severity of the clinical picture. Anxiety, insomnia and drug response however showed significant correlation with pretreatment 5-HIAA level. Some possible interpretations are discussed.
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PMID:Correlation of anxiety and related symptoms with cerebrospinal fluid 5-hydroxyindoleacetic acid in depressed women. 91 3

1. Monoamine neurotransmitters (epinephrine, norepinephrine, dopamine, serotonin and some of their metabolites (DOPEG, MHPG, DOPAC, 5-HIAA) were measured by HPLC in extracts from telencephalon (TEL) and diencephalon-midbrain (DM) before, during at the end of metamorphosis. 2. During metamorphosis MHPG increased and 5-HIAA decreased in TEL and DM while DOPEG decreased only in DM. 3. Monoamine levels were greater in the TEL and a larger increase in MHPG occurred there. 4. Captivity without metamorphosis also caused a significant depression of 5-HIAA in TEL and depression of DOPEG, MHPG and DOPAC in DM.
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PMID:Monoamines and their metabolites in the amphibian (Ambystoma tigrinum) brain: quantitative changes during metamorphosis and captivity. 135 51

5-HT disturbances in depression (as exemplified by lowered CSF 5-HIAA) are not syndrome specific but related to components of the depressive syndrome, specifically to increased anxiety and aggression. These 5-HT disturbances are probably core pathogenetic processes not derivative features. I hypothesized that in this subtype of depression, i.e. in "5-HT related depression", the key psychopathological disturbances are dysregulation of anxiety and aggression, while mood lowering is a "by-product". Based on this hypothesis it was predicted that agents which ameliorate anxiety and/or aggression via harmonization of 5-HT ergic transmission will, in addition, exert overall antidepressant effect in "5-HT related depression". The study of the relative "weight" of the various psychopathological components of depression is a basic exercise in understanding the nature of that condition and could, as such, greatly facilitate the goal-directed search for new and innovative antidepressants.
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PMID:About the centrality of mood lowering in mood disorders. Plenary Lecture ECNP Congress, Monte Carlo, October 1991. 136 59

We describe the production of an experimental model of parkinsonism induced by cinnarizine (CNZ) in three healthy sylvanna monkeys. The drug produced a severe but reversible parkinsonism in all animals. After discontinuation of CNZ, all animals recovered but the oldest one was akinetic for 6 weeks. CNZ produced a persistent reduction in HVA and 5-HIAA levels in the CSF. Our data suggest a predominant presynaptic effect on DA and 5-HT neurons; and could account for the longstanding parkinsonism induced by calcium antagonist in some patients as well as the depression observed in these subjects.
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PMID:Cinnarizine-induced parkinsonism in primates. 137 37

Monoamine metabolites were measured in the cerebrospinal fluid (CSF) of depressed and nondepressed patients with acute stroke lesions and in nondepressed patients without stroke lesions. Depressed stroke patients had a significantly lower concentration of CSF 5-hydroxyindoleacetic acid (5-HIAA; a serotonin metabolite) than the other two groups. These findings suggest that poststroke depression may be mediated by serotonergic mechanisms.
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PMID:Reduction of CSF monoamine metabolites in poststroke depression: a preliminary report. 138 52

Ablation of olfactory bulbs in rats reduced male sexual behavior, and altered the distribution of wheel-running activity between the light and dark phases of a 12:12 LD photoperiod. These effects were partially reversed by the tricyclic antidepressant amitriptyline. Olfactory bulbectomy also altered serotonin metabolism (5-HIAA/5-HT ratio) in the frontal cortex, nucleus accumbens, hippocampus and corpus striatum. These observations support the hypothesis that olfactory bulbectomy in rodents serves as a model of agitated hyposerotonergic depression.
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PMID:Olfactory bulbectomy as a model for agitated hyposerotonergic depression. 152 54


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