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)

Although a putative role has been attributed to inflammation in the pathogenesis of depressive disorders, the relationship of prostaglandins, known mediators of inflammation, and depression has not been elucidated. Clomipramine is an antidepressive drug with a pro-depressive paradoxical effect in adult rats when administrated neonatally. Using this effect as a model of depression, we investigated the differential expression of the cyclooxygenase (COX-2) gene in rat brains. Rats injected neonatally with clomipramine showed depressive-like symptoms in adulthood, as well as decreased levels of the brain-derived neurotrophic factor (BDNF) and a quantitative differential expression of the COX-2 gene (Real Time PCR) and protein (immunohistochemistry) in the hippocampus. As evidenced, the relationship between a key enzyme in the prostaglandin synthesis and biological and behavioral depression-like changes opens an interesting line of investigation regarding the molecular bases of depression and its potential treatment through immunomodulatory drugs.
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PMID:Hippocampal upregulation of the cyclooxygenase-2 gene following neonatal clomipramine treatment (a model of depression). 1656 49

Recent studies suggest several problems associated with selective serotonin reuptake inhibitors (SSRIs) when administered during pregnancy. During organogenesis, paroxetine (Deroxat, Paxil, or generics) was associated with a significantly increased risk of major congenital malformations. Such an increase had already been reported with clomipramine (Anafranil), a tricyclic antidepressant. After the time of organogenesis, SSRIs have also been associated to risks. Of these, the more frequent is neonatal toxicity, while pulmonary hypertension in the newborn is likely to be the more severe. These newly discovered side effects arouse questions about the treatment of depression during pregnancy.
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PMID:[Selective serotonin reuptake inhibitors (SSRIs) in pregnancy]. 1668 31

Clomipramine ushered in a new age of pharmacotherapy for obsessive-compulsive disorders, and it also facilitated our understanding of the biological aspects of obsessive-compulsive disorder, focusing on the serotonergic systems. The introduction of selective serotonin reuptake inhibitors has led to great progress in the pharmacological study of obsessive-compulsive disorder based on the serotonin hypothesis. Currently, selective serotonin reuptake inhibitors are positioned as a first-line drug of obsessive-compulsive disorder pharmacotherapy in the various guidelines and algorithms. Among six different selective serotonin reuptake inhibitors (paroxetine, sertraline, fluoxetine, fluvoxamine, citalopram, escitalopram) that are available worldwide, paroxetine has the broadest treatment spectrum and promises great benefits not only for obsessive-compulsive disorder patients, but also for those with comorbid depression and/or various kinds of anxiety disorders. This paper presents several clinical trials of paroxetine carried out, and discusses and reviews the therapeutic strategies for obsessive-compulsive disorder.
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PMID:Effectiveness of paroxetine in the treatment of obsessive-compulsive disorders. 1683 Nov 10

The authors report an improvement in delusions and hallucinations after antidepressant treatment (Clomipramine) in a parkinsonian patient with psychosis and comorbid depression. Their findings, which support a previous case treated with Citalopram, highlight the possible effectiveness of antidepressant therapy on psychotic symptoms in parkinsonian patients.
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PMID:Antidepressant use in treatment of psychosis with comorbid depression in Parkinson's disease. 1691 77

Treatment of obsessive compulsive disorder has not changed a lot since 2000. Following a cautious assessment of the patient, using adequate scales, OCD patients require a step by step hierarchical treatment. A syndrome of low intensity (Yale-Brown Obsessive Compulsive Score [Y-BOCS] around 15) will be mainly treated by behavioural and cognitive therapy (BCT) especially exposition with prevention of response technique; for a more severe disorder, a drug treatment is required. Selective serotonin reuptake inhibitors (SSRI) are firstly recommended. They should be used in monotherapy with daily doses higher than those used for depression. Response is slow and usually delayed comparing to the alleviation of the depressive syndrome. A full response with disappearance of the symptoms is an exception. A good response to an antiobsessive treatment affords a 50% reduction of the intensity of OCD. Clomipramine may be slightly more effective than SSRI. Once, an improvement has been obtained, the drug titration should be kept for at least 18 to 24 months before attempting to discontinue medication. In case of non response, switching SSRI drug, combination with BCT may contribute to resolve the problem. In treatment refractory OCD, combination with either risperidone or olanzapine has shown some effective results in controlled trials. Finally, for several infrequent patients with a "malignant syndrome", functional neuro-surgery using deep brain stimulation might be a safe and hopeful therapeutic technique.
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PMID:[Treatment of obsessive-compulsive disorder]. 1743 2

Evidence exists for a dopaminergic system dysregulation in mood disorders. In particular, depression may be accompanied by a relative fall of brain dopamine (DA) availability, while the increase of dopamine D2/D3 receptors (D2R/D3R) binding may reflect a compensatory change following primary reduction of mesolimbic DA levels. It is well established that D3Rs, acting as autoreceptors, inhibit DA synthesis and release, although lack of selective compounds have limited the progress in understanding D3Rs role in mood disorders. Aim of this study was to assess the behavioral responses of D3R-deficient (D3(-/-)) mice tested in the forced swim test (FST) and to evaluate their sensitivity to the treatment with different antidepressant drugs. Different groups of mice received one injection of the tricyclic compound, clomipramine (1, 5 and 10 mg/kg) or of one the selective serotonin reuptake inhibitors (SSRIs), paroxetine, sertraline or citalopram (1, 4 and 16 mg/kg), 30 min prior the behavioral test. Vehicle-injected wild type (WT) mice and D3(-/-) animals were used as controls and submitted to the same experimental procedure. In a preliminary experiment, vehicle-injected D3(-/-) mice, but not their littermates, failed to show an increased immobility time in FST as compared to intact controls, suggesting an increased resistance to injection-induced stress in the former. Clomipramine 1 mg/kg failed to affect behavioral responses of both D3(-/-) mice and WT animals. After the 5 mg/kg dose, D3(-/-) and WT mice showed a better performance in FST than vehicle-injected controls, with a lower immobility time exhibited by D3(-/-) mice than that shown by WT animals. No difference was found between WT mice treated with the highest dose of clomipramine (10 mg/kg) and the respective controls, although D3(-/-) mice exhibited a decreased immobility time as compared to vehicle-injected controls. In contrast to WT animals, when treated with 1 mg/kg sertraline and the 4 mg/kg dose of every SSRI D3(-/-) mice exhibited a decreased immobility time in FST in comparison to vehicle-injected controls. Furthermore, 16 mg/kg doses of citalopram, paroxetine or sertraline induced a greater reduction of immobility time in D3(-/-) mice than in WT-treated animals as compared to their respective controls. These data suggest that D3(-/-) mice, as being more resistant to stressful procedure than WT littermates, are more sensitive to antidepressants in FST paradigm than the former. Although the present data do not allow any conclusion on the neurochemical base of this difference, it might be possible that the greater sensitivity to antidepressants depends on a higher DA levels in mesolimbic pathways following the lack of D3Rs.
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PMID:Increased sensitivity to antidepressants of D3 dopamine receptor-deficient mice in the forced swim test (FST). 1780 7

Substance P (SP) is possibly involved in the pathophysiology of depression and anxiety. We investigated interactions between antidepressants on SP-induced effects and their potential calcium-blocking activity in the isolated guinea pig ileum. All the antidepressants tested, except pargyline, moclobemide, mianserin, and reboxetine, were able to inhibit in a concentration-dependent manner the contraction induced by 100 nmol/L SP. Clomipramine, fluoxetine, maprotiline, and amitriptyline (all at 3 mumol/L) flattened the concentration-response curves to SP, resulting in a reduction of up to 59%, 63%, 32%, and 23%, respectively, of the maximum contractile effect. All the antidepressants tested (3 mumol/L), except pargyline, moclobemide, and mianserin, produced a rightward parallel shift of the concentration-response curve to CaCl2. The L-type selective calcium blocker nifedipine and the T-type selective mibefradil showed similar behaviour against both agonists used, SP and CaCl2. The relative order of potency was nifedipine (pA2, 7.6 +/- 0.1) > clomipramine (pA2, 7.0 +/- 0.1) > fluoxetine (pKB, 6.5 +/- 0.1) = mibefradil (pKB, 6.6 +/- 0.1) > amitriptyline (pKB, 6.3 +/- 0.1) = maprotiline (pKB, 6.2 +/- 0.1) > fluvoxamine (pKB, 5.9 +/- 0.1). The data reported in the present study suggest that the antidepressants tested did not behave as competitive antagonists versus NK1-receptor subtypes, but their inhibitory action seems to be related to their calcium-blocking properties.
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PMID:Older versus newer antidepressants: substance P or calcium antagonism? 1806 1

The open comparative study of three antidepressants with different mechanisms of action - clomipramine, pirlindole and escitalopram - in the treatment of neurotic level depression (ICD-10 items F32-F34, F43) has been carried out. Ninety-one patients have been stratified into three groups included 31, 31 and 29 patients, respectively.. Duration of the study has been 12 weeks. Clomipramine, pirlindole and escitalopram have similar effect decreasing the total HAMD score by more than 50% (in average 72%). Clomipramine appears to be more effective in the achievement of remission (63%) as compared to pirlindole (40%) and escitalopram (42%). The tolerability of pirlindole and escitalopram is higher than that of clomipramine and the authors recommend prescription of these drugs to patients with neurotic depression.
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PMID:[Efficacy and tolerability of clomipramine, pirlindole and escitalopram in the treatment of neurotic level depression]. 1842 38

Growing evidence suggests the involvement of glutamate in mood disorders and in the response to antidepressants. However, there is no information regarding a hypothesized sex-dependent glutamatergic modulation following treatment in animal models of depression. We comparatively assayed in male and female Flinders and control Sprague-Dawley rats glutamate and aspartate tissue levels in the prefrontal cortex, hippocampus and nucleus accumbens following 14-day treatment with either 10mg/kg clomipramine or mirtazapine, intraperitoneally. Clomipramine increased cortical glutamate in both sexes and hippocampal glutamate only in female Flinders rodents. Mirtazapine had no effect on cortical glutamate content but increased hippocampal glutamate in both Flinders sexes. Neither mirtazapine nor clomipramine altered glutamate levels in the nucleus accumbens. There were no any significant differences in aspartate levels. However, in control male SD rats clomipramine and mirtazapine significantly decreased cortical aspartate levels. Our results indicate that two different types of established antidepressants induce a brain region-specific effect on glutamate content. This effect is also characterized by sex-dependent differences mainly in the hippocampus, highlighting a differentiated response of glutamate to distinct antidepressants.
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PMID:Antidepressants induce regionally discrete, sex-dependent changes in brain's glutamate content. 1966 87

The character of changes of open field behavior was not studied extensively in animal model of depression with deficiency of brain monoamine/serotonin content and obtained results are controversial. Both, enhancement and invariability of locomotor activity has been obtained. Additional investigation of this question is motivated also by insufficient study of exploratory and emotional behaviors in animal model of depression of this type. Animal model of depression was developed by chronic administration of Clomipramine and/or Melipramine in rat pups from postnatal day 7 (P7) and/or 14 (P14) to P21 and/or P28, respectively. Studies of open field behavior were started in adult age rats i.e. 8-12 weeks after the end of treatment. Control animals were the same age old. Two-week period of postnatal development starting at the P7 and/or P14 appeared equally sensitive to early antidepressant treatment. Modeled animals exhibited significant increase of horizontal locomotor activity. Frequency of center entrance and the time of staying in the center of open field were increased significantly indicating that animal models of depression can not percept really the level of stressfulness of novel surroundings. All of these changes indicate also to the significant level of exploratory behavior in modeled animals. Postnatal exposure of rat pups to Clomipramine or Melipramine produces significant increase of locomotor activity but dos not induces behavioral 'despair' or "refractory loss of interest" at mature age.
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PMID:Changes of locomotor, exploratory and emotional behavior in animal model of depression induced by deficiency of brain monoamine content. 2215 82


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