Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Imipramine administration (50 mg kg-1, i.p.) to Sprague-Dawley male rats (240-290 g) 6 or 10 h after CCl4 (1 ml kg-1, i.p.) partially prevents liver necrosis induced by the hepatotoxin. When imipramine is given 30 min before CCl4, it inhibits in part the CCl4-induced lipid peroxidation and the covalent interactions of reactive metabolites with microsomal lipids or proteins and partially prevents CCl4-induced cytochrome P-450 destruction, but not glucose 6 phosphatase activity depression. Imipramine administration prior to CCl4 does not modify levels of the hepatotoxin reaching the liver or the body temperature of CCl4 treated animals. Early preventive effects of imipramine on cytochrome P-450, might be attributed to inhibition of covalent interactions of reactive metabolites. The hypothesis that imipramine exerted late preventive effects by interfering with calcium deleterious effects or by modulation of protein and phospholipid synthesis or degradation is analyzed.
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PMID:Imipramine prevention of carbon tetrachloride-induced liver necrosis at late states of the intoxication process. 302 54

3H-Imipramine (3H-IMI) binding to platelet membranes was measured in 19 patients with agoraphobia with panic attacks, 9 patients with major depression, and 22 healthy subjects. In comparison to healthy subjects, the maximal number of binding sites (Bmax) was significantly decreased in depressed patients but not in panic disorder patients, and the apparent affinity of binding was slightly decreased in depressed patients but not in panic disorder patients. The Bmax and Kd of 3H-IMI platelet binding did not differ between panic disorder patients with and without a history of a major depressive episode. Thus, 3H-IMI platelet binding is clearly different in patients with panic disorder compared to those with an active depression. Because 3H-IMI binding is associated with the serotonin reuptake site in platelet and brain membranes, these findings give further support to abnormalities in serotonergic function in patients with major depression.
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PMID:Differential 3H-imipramine platelet binding in patients with panic disorder and depression. 303 80

[3H]-Imipramine and [3H]-paroxetine label with high affinity a site which is associated with the serotonergic transporter in brain and platelets. The pharmacological profile of inhibition by drugs of [3H]-imipramine and [3H]-paroxetine binding is highly correlated with the potency of the drugs to inhibit the uptake of 5HT. Denervation of serotonergic neurons by electrolytic lesions or with 5,7-dihydroxytryptamine produces marked decreases in the density of [3H]-imipramine as well as [3H]-paroxetine binding. Dissociation kinetic experiments support the view that the substrate recognition site for 5HT is different from the modulatory site which is labelled by [3H]-imipramine or [3H]-paroxetine. The existence of an endogenous ligand acting on the [3H]-imipramine recognition site to modulate the 5HT transporter was proposed by several laboratories. [3H]-Imipramine binding in platelets appears to be a biological marker in depression. Studies carried out in several laboratories report a significant decrease in the Bmax of platelet [3H]-imipramine binding without changes in Kd, when severely depressed untreated patients are compared with healthy volunteers matched for age and sex. The Bmax of platelet [3H]-imipramine binding appears to be a state-dependent biological marker in depression. It is tempting to speculate that the endocoid of the [3H]-imipramine recognition site may play a role in the pathogenesis of depression.
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PMID:Association of [3H]-imipramine and [3H]-paroxetine binding with the 5HT transporter in brain and platelets: relevance to studies in depression. 304 Sep 83

Depression prevails in 12-13% of the elderly, of whom a 5th suffer major depressive illness. First admission-rates to psychiatric beds in England increase with aging until the 80s, when they fall off in women but continue to rise in men. Physical illness is a considerable contributor to depression in old age, and consequently depression is more prevalent in elderly general hospital inpatients than in the community. Better screening instruments are needed to detect this depression, and the place of antidepressant therapy needs to be better established. All antidepressants fall short of the ideal, particularly through acting slowly, having side-effects and being dangerous in overdose. Justifiably popular though dothiepin is in the treatment of depression in the elderly, its fatal toxicity index is high. Lofepramine appears to be as effective, to have fewer side-effects and to be safer, but experience of it is relatively meagre in the elderly and satisfactory double-blind comparisons with suitable control drugs in this age group have yet to be reported. If it lives up to its present promise it may be particularly suitable for the physically ill and depressed elderly.
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PMID:Lofepramine in the elderly. 306 44

Gilles de la Tourette's syndrome (GTS) is a chronic neuropsychiatric disorder characterized by multiple involuntary motor and phonic tics associated with behavioural disturbances including obsessive-compulsive and aggressive behavior, depression and, rarely, psychosis. The relationship of GTS, presumed to be predominantly a dopaminergic disorder, and depression, presumed to be a noradrenergic-serotoninergic deficiency state, is currently poorly understood. The reports published to date on the effects of tricyclic antidepressants in GTS have been contradictory; while Messiha et al. (1976) used imipramine successfully in one GTS patient, Abuzzahab and Anderson (1973) and Fras (1978) on the other hand, found imipramine to exacerbate GTS symptoms and cautioned its usage in this syndrome. A more recent report suggested that imipramine is useful in GTS patients who exhibit symptoms of attention deficit disorder (Dillon et al., 1985). We report a patient with GTS whose depression and behaviour improved considerably when low-dose imipramine (Tofranil) was added to the regimen of anti-GTS medication. This report suggest that tricyclic antidepressants may be useful adjuncts in the management of GTS, and hints at norepinephrinergic and serotoninergic deficiencies as being components of the pathogenesis of the syndrome.
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PMID:Beneficial effects of imipramine on Tourette's syndrome. 316 8

One hundred nineteen patients who met specific criteria for atypical depression completed six weeks of double-blind, randomly assigned treatment with phenelzine sulfate, imipramine hydrochloride, or placebo. The overall response rates were 71% with phenelzine, 50% with imipramine, and 28% with placebo. Phenelzine was widely superior to placebo and also showed superiority to imipramine. Phenelzine superiority appeared even greater after an additional six-week continuation phase. Imipramine was only moderately effective in this atypical depressive sample. Unexpectedly, the superiority of either phenelzine or imipramine to placebo was largely confined to patients in subsets of the study sample who were prospectively judged to also have a history of spontaneous panic attacks and/or show hysteroid dysphoric features. This is consonant with some but not other recent findings and requires replication. Overall, the concept of atypical depression as a subtype that is preferentially responsive to monoamine oxidase inhibitors is supported.
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PMID:Antidepressant specificity in atypical depression. 327 82

Two hundred forty-one outpatients with a DSM-III diagnosis of major depressive disorder participated in a six-week double-blind therapeutic trial of alprazolam, diazepam, imipramine hydrochloride, and placebo. Side effects were given as a major reason for attrition by patients taking the three active compounds and ineffectiveness was the reason given by patients taking placebo. Imipramine-treated patients reported the most and placebo patients the least number of adverse effects. Imipramine and alprazolam, but not diazepam, produced significantly more improvement in depressed symptomatology than did placebo. Mean diazepam scores frequently assumed an intermediate position between those of imipramine or alprazolam and placebo. These treatment differences were found to be independent of initial severity levels of anxiety and depression.
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PMID:Alprazolam, diazepam, imipramine, and placebo in outpatients with major depression. 331 Sep 52

The authors compared the effects of 6 weeks of imipramine treatment with 6 weeks of placebo treatment on social and vocational impairment in chronic depression. Imipramine was associated with significantly greater pre- to posttreatment improvement of social-vocational impairments in chronic depression, suggesting that these impairments may have represented affective symptoms rather than characterologic deficits.
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PMID:Imipramine and social-vocational adjustment in chronic depression. 339 86

There is a need for safe effective alternatives to benzodiazepines in the treatment of panic disorder. Buspirone, a new nonbenzodiazepine anxiolytic, is compared to imipramine and placebo in the treatment of panic disorder in an 8 week double-blind controlled study of 52 randomly assigned patients. Weekly assessments were made using the Hamilton Anxiety Scale, the Sheehan Clinician Rated Anxiety Scale, the Sheehan Patient Rated Anxiety Scale, the Phobia Scale, the Disability Scale, the Hamilton Depression Scale, the Montgomery Asberg Depression Scale, the Investigator Rated Global Improvement Scale and the Patient Rated Global Improvement Scale. Preliminary results of repeated measures Anovas are reported. Imipramine was superior to placebo on many of the outcome measures. Imipramine was superior to buspirone on the Patient Rated Global Improvement Scale and on the Investigator Rated Global Improvement Scale, but not on other measures. Although buspirone appeared to be more effective than placebo, differences were not statistically significant. Some buspirone patients did very well compared to others, suggesting a possible bimodal distribution of response. Patients on buspirone had fewer and less disruptive side effects than those on imipramine.
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PMID:The relative efficacy of buspirone, imipramine and placebo in panic disorder: a preliminary report. 341 3

We randomly assigned 425 outpatients, independently classified as primarily depressed by two trained psychiatrists, to double-blind treatment with Imipramine hydrochloride, chlordiazepoxide hydrochloride, or placebo. Those patients who remained at least moderately depressed (following a two-week placebo washout period) were treated for an additional eight weeks. An endpoint analysis of 387 patients who completed two or more weeks of medication disclosed early therapeutic advantages of chlordiazepoxide. By week 4 of treatment, however, imipramine produced more improvement than did placebo and chlordiazepoxide. By six and eight weeks a general, marked therapeutic advantage was found for imipramine relative to placebo and to chlordiazepoxide on measures of depression, anxiety, anger-hostility, interpersonal sensitivity, and global improvement. Chlordiazepoxide-treated patients generally did significantly better on sleep difficulty but significantly worse on anger-hostility and interpersonal sensitivity than did imipramine- or placebo-treated patients.
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PMID:Imipramine and chlordiazepoxide in depressive and anxiety disorders. I. Efficacy in depressed outpatients. 351 Jun 1


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