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)

In a 4-week double-blind clinical trial we compared the effects of the tricyclic antidepressants trimipramine and imipramine on the sleep EEG and on nocturnal bormone secretion in 20 male inpatients with major depression. Both treatments produced rapid significant clinical improvement in depression without severe adverse effects. However, the two drugs had markedly different neurobiologic profiles. Trimipramine enhanced rapid eye movement (REM) sleep and slow wave sleep, whereas imipramine suppressed REM sleep and showed no effect on slow wave sleep. Total sleep time and the sleep efficiency index increased under trimipramine but not under imipramine. Nocturnal cortisol secretion decreased with trimipramine but remained unchanged with imipramine. In contrast to imipramine, trimipramine induced an increase in prolactin secretion compatible with its known antagonism at dopamine (D2) receptors. Imipramine induced a decrease in growth hormone secretion during the first half of the night. Neither of the drugs induced significant changes in plasma testosterone concentration. We conclude that trimipramine is an antidepressant with sleep-improving qualities that possibly acts through inhibition of hypothalamic-pituitary-adrenocortical system activity by a yet unknown mechanism.
Depression 1996
PMID:Trimipramine and imipramine exert different effects on the sleep EEG and on nocturnal hormone secretion during treatment of major depression. 916 Jun 49

The authors compared the effectiveness of Cognitive Behavioral Therapy (CBT), Interpersonal Psychotherapy (IPT), Imipramine Clinical Management (ICM) to Placebo Clinical Management (PCM) for outpatients with early-onset chronic depression (N = 65) in the National Institute of Mental Health (NIMH) Treatment of Depression Collaborative Research Program (TDRP). The post-treatment depression scores of the CBT. IPT, and ICM groups were not significantly different from the PCM group. We did not find a relationship between the duration of Major Depression and response to a specific treatment. Studies are needed to determine if combining psychotherapy with medication improves social functioning and enhances the quality of life for patients with chronic depression.
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PMID:The efficacy of imipramine and psychotherapy in early-onset chronic depression: a reanalysis of the National Institute of Mental health Treatment of Depression Collaborative Research Program. 918 88

At the Drug Detoxification Program of the Haight Ashbury Free Clinics, we conducted a randomized clinical trial of imipramine in the treatment of methamphetamine dependence. The purposes of the trial were to test the efficacy of imipramine as a treatment for methamphetamine dependence and to establish the feasibility of conducting a controlled clinical trial at the Clinic. Thirty-two subjects were randomly assigned to receive either 10 or 150 mg/day of imiprine for 180 days. Imipramine 10 mg/day was the control. Subjects received intensive counseling. Retention in treatment was significantly longer for subjects who were treated with 150 mg of imipramine compared to control (median days: 33.0 vs. 10.5). There were no consistent differences in percent of urine samples positive for methamphetamine, Beck Depression Inventory scores, or craving. Determination of the full extent of imipramine's utility in the treatment of methamphetamine dependence awaits a larger trial.
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PMID:A controlled trial of imipramine for the treatment of methamphetamine dependence. 921 47

The hypercortisolism of melancholic depression is thought to reflect hypothalamic hypersecretion of CRH and may be related to the hyperarousal associated with this syndrome. Although chronic administration of imipramine to experimental animals significantly decreases CRH messenger RNA levels in the paraventricular nucleus, it is generally thought that resolution of hypercortisolism following recovery from depression is related to the improvement in mood and decrease in anxiety that accompanies recovery rather than an intrinsic effect of imipramine. The present study was designed to explore whether chronic imipramine administration to healthy, nondepressed volunteers is associated with effects on hypothalamic-pituitary-adrenal (HPA) axis function. We studied basal and provocative measures of HPA axis function in 14 healthy volunteers before and after 6 weeks of imipramine treatment at therapeutic doses. Imipramine was associated with decreased responses in peak ACTH and cortisol to ovine CRH and in peak ACTH to arginine vasopressin (P = 0.02, P = 0.003, and P = 0.02, respectively) without changes in indices of basal HPA axis function. These data are consistent with preclinical findings and support the hypothesis that imipramine has an intrinsic effect on central components of HPA axis function, potentially related to its therapeutic effects.
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PMID:Chronic imipramine is associated with diminished hypothalamic-pituitary-adrenal axis responsivity in healthy humans. 925 41

We present the case of a 35-year-old woman who developed serotonin syndrome after receiving a single dose of the cyclic antidepressant imipramine (Tofranil). She was already being treated for depression with paroxetine (Paxil), a selective serotonin reuptake inhibitor. Two hours after receiving imipramine, the patient developed tachycardia, delirium, bizarre movements, and myoclonus, all classic findings of serotonin syndrome. Her antidepressants were discontinued and she was treated with intravenous fluids, sedation, and a short course of cyproheptadine, a serotonin receptor antagonist. All symptoms resolved completely within 24 hours. In this case report, we review the drug interactions that can precipitate serotonin syndrome, and give recommendations for the diagnosis and treatment of this potentially fatal disorder.
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PMID:Serotonin syndrome: case report and review of the literature. 941 60

1. Alterations of 5-hydroxytryptaminergic mechanisms are thought to play a special role in the pathogenesis of depression and antidepressant treatments are assumed to restore these changes. 2. We have used one of the most reliable models of depression, the olfactory bulbectomized rat to study the long term consequences of this manipulation and of subchronic imipramine treatment on two parameters of 5-hydroxytryptaminergic presynapses, 5-hydroxytryptamine (5-HT) transporter density and tryptophan hydroxylase apoenzyme concentration, in the frontal cortex as well as on active avoidance learning several weeks after bulbectomy. 3. The Bmax value of [3H]-paroxetine binding and the concentration of the 5-HT synthesizing enzyme were both significantly elevated in the frontal cortex of bulbectomized rats compared to sham-operated controls. 4. Imipramine treatment, either by daily injections or by subcutaneous implantation of slow release imipramine-containing polymers reduced the elevated tryptophan hydroxylase apoenzyme levels in the frontal cortex of bulbectomized, but not of sham-operated control rats and restored the deficient learning performance of bulbectomized rats. 5. Both effects were more pronounced after continuous drug administration by imipramine-releasing polymers compared to daily i.p. injections. 6. These findings indicate that bulbectomy leads to a compensatory 5-hydroxytryptaminergic hyperinnervation of the frontal cortex. Chronic antidepressant treatment seems to attenuate the increased output of the 5-hydroxytryptaminergic projections in the frontal cortex through the destabilization of the rate limiting enzyme of 5-HT synthesis of the 5-hydroxytryptaminergic nerve endings in this brain region.
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PMID:Influence of olfactory bulbectomy and subsequent imipramine treatment on 5-hydroxytryptaminergic presynapses in the rat frontal cortex: behavioural correlates. 942 20

There is an increasing body of evidence suggesting that GABA plays an important role in the therapeutic effects of antidepressant/antipanic drugs. Phenelzine and imipramine are efficacious in the treatment of depression and panic disorder and phenelzine has been reported to elevate GABA levels while imipramine enhances GABA release in rat brains. In the present study, using a multiprobe quantitative solution hybridization assay, we measured the steady-state levels of mRNAs that encode glutamic acid decarboxylase (GAD67 and GAD65), the GABA transporter GAT-1 and GABA transaminase (GABA-T) in rat cortex after treatment with constant infusion (via osmotic minipumps) of phenelzine or imipramine for a short-term (3 days) or long-term (21 days) period. We found that none of the treatments gave rise to significant changes in the steady-state levels of mRNAs encoding GAD67, GAD65 or GABA-T at any time point. The steady-state levels of GAT-1 mRNA were increased significantly (23%) after long-term, but not by short-term, treatment with phenelzine. Imipramine treatment, short- or long-term, did not alter the steady-state levels of GAT-1 mRNA. These results suggest that the GABA enhancing effects of phenelzine or imipramine in rat cortex do not affect the steady-state levels of mRNAs that encode GAD67, GAD65 and GABA-T. Further, the previously observed increases in GABA levels or GABA release induced by these drugs are probably not a consequence of changes in the expression of these genes.
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PMID:Effects of phenelzine and imipramine on the steady-state levels of mRNAs that encode glutamic acid decarboxylase (GAD67 and GAD65), the GABA transporter GAT-1 and GABA transaminase in rat cortex. 945 70

1. Effects of substances which are able to alter brain histamine levels and two histamine H1 receptor agonists were investigated in mice by means of an animal model of depression, the forced swim test. 2. Imipramine (10 and 30 mg kg(-1), i.p.) and amitriptyline (5 and 15 mg kg(-1), i.p.) were used as positive controls. Their effects were not affected by pretreatment with the histamine H3 receptor agonist, (R)-alpha-methylhistamine, at a dose (10 mg kg(-1), i.p.) which did not modify the cumulative time of immobility. 3. The histamine H3 receptor antagonist, thioperamide (2-20 mg kg(-1), s.c.), showed an antidepressant-like effect, with a maximum at the dose of 5 mg kg(-1), which was completely prevented by (R)-alpha-methylhistamine. 4. The histamine-N-methyltransferase inhibitor, metoprine (2-20 mg kg(-1), s.c.), was effective with an ED50 of 4.02 (2.71-5.96) mg kg(-1); its effect was prevented by (R)-alpha-methylhistamine. 5. The histamine precursor, L-histidine (100-1000 mg kg(-1), i.p.), dose-dependently decreased the time of immobility [ED30 587 (499-712) mg kg(-1)]. The effect of 500 mg kg(-1) L-histidine was completely prevented by the selective histidine decarboxylase inhibitor, (S)-alpha-fluoromethylhistidine (50 mg kg(-1), i.p.), administered 15 h before. 6. The highly selective histamine H1 receptor agonist, 2-(3-trifluoromethylphenyl)histamine (0.3-6.5 microg per mouse, i.c.v.), and the better known H1 agonist, 2-thiazolylethylamine (0.1-1 microg per mouse, i.c.v.), were both dose-dependently effective in decreasing the time of immobility [ED50 3.6 (1.53-8.48) and 1.34 (0.084-21.5) microg per mouse, respectively]. 7. None of the substances tested affected mouse performance in the rota rod test at the doses used in the forced swim test. 8. It was concluded that endogenous histamine reduces the time of immobility in this test, suggesting an antidepressant-like effect, via activation of H1 receptors.
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PMID:Antidepressant-like effects of endogenous histamine and of two histamine H1 receptor agonists in the mouse forced swim test. 957 27

Various studies suggest alpha 2-adrenergic receptor (alpha 2AR) dysregulation in panic disorder (PD). Platelet alpha 2-AR exist in high- and low-conformational states as a function of their coupling to Gi protein. alpha 2AR coupling is important in signal transduction and is modulated by antidepressants. alpha 2AR density in the high- and low-conformational states, agonist affinity, and coupling efficiency were investigated in 21 healthy controls, 21 drug-free PD patients, and eight imipramine-treated patients using norepinephrine displacement of 3H-yohimbine binding. Percentage of receptors in the high-conformational state (%RH) and the ratio of the agonist dissociation constant to the receptor in the low-/high-conformational state (KL/KH), calculated from displacement experiments, were used as coupling indices. Patients had high alpha 2AR density in both conformational states. %RH and KL/KH ratio were significantly different, particularly in patients with Hamilton scale for depression (HAMD) scores > or = 15. Imipramine treatment (29 weeks) had no effect on alpha 2AR density or coupling, despite improvement in anxiety ratings. High pretreatment alpha 2AR density and coupling predicted low severity of anxiety after treatment. Increased alpha 2AR density and abnormal coupling may represent an adaptive mechanism or trait marker in PD.
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PMID:Adrenergic receptor function in panic disorder. I. Platelet alpha 2 receptors: Gi protein coupling, effects of imipramine, and relationship to treatment outcome. 988 96

1. S-adenosyl-L-methionine (SAMe) is the most important methyl donor in the brain and is essential for polyamine synthesis. Methyl group deficiency in the brain has been implicated in depression; on the other hand, polyamines enhance phosphorylation processes, and phosphorylation of functional proteins in neurons in involved in the therapeutic mechanisms of antidepressants. 2. The effect of SAMe in an animal model of 'depression', the chronic mild stress-induced anhedonia, was studied using long-term castrated male and female Lister hooded rats. 3. Chronic daily exposure to an unpredictable sequence of mild stressors produced, within 3 weeks, a significant reduction of the consumption of a sucrose solution. SAMe (100, 200 or 300 mg kg-1 daily i.m.) while having no influence on sucrose intake in non-stressed animals, dose-dependently reinstated sucrose consumption within the first week of treatment, both in male and in female stressed rats. Imipramine (10 mg kg-1 daily i.p.) produced a similar effect after a 3 week treatment. 4. Similarly, a palatable food reward-induced place preference conditioning was developed in SAMe (200 or 300 mg kg-1 daily i.m.)--and in imipramine (10 mg kg-1 daily i.p.)--treated chronically stressed animals (males and females), whilst it could not be obtained in vehicle-treated rats. 5. Moreover, the same doses of SAMe (but not of imipramine) restored the exploratory activity and curiosity for the environment (rearing), in the open-field test. 6. While imipramine caused a blockade of the growth throughout the treatment, SAMe produced only a transient growth arrest during the first week of treatment. 7. These results show that SAMe reverses an experimental condition of 'depression-like' behaviour in rats, the effect being more rapid and complete than that of imipramine, and without apparent side effects.
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PMID:Influence of S-adenosyl-L-methionine on chronic mild stress-induced anhedonia in castrated rats. 1040 54


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