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)

A double-blind comparison of zimelidine, a potent and fairly selective 5-hydroxytryptamine (5-HT) uptake inhibitor, and desipramine, a noradrenaline (NA) uptake inhibitor, was carried out in hospitalized patients with endogenous depression. The patients were randomized into parallel groups receiving either zimelidine 100 mg b.i.d. or desipramine 75 mg b.i.d. Forty patients completed the study, twenty in each treatment group. Patients who did not respond adequately to one drug after 4 weeks were treated with the other drug (cross-over design) after a washout period. For evaluation of the therapeutic efficacy Hamilton Rating Scale for Depression, Comprehensive Psychopathological Rating Scale for Depression, Beck's Inventory and Global Rating Scales were used. All ratings indicated greater effectiveness for zimelidine as compared with desipramine, although the differences were not generally statistically significant. Only "somatic anxiety" on the Hamilton scale was significantly (P less than 0.05) in favour of zimelidine. Although both zimelidine and desipramine were well tolerated, the zimelidine patients reported significantly less severe anticholinergic adverse reactions. Of five patients who did not improve on zimelidine, three were then given desipramine but only one recovered completely. Of 10 patients who were switched over to zimelidine, 6 recovered completely and one moderately. Zimelidine produced strong inhibition of the uptake of 5-HT in platelets and a decrease in blood 5-HT after 2 weeks or longer treatment. The uptake of 5-HT in rat hypothalamic synaptosomes was reduced by about 50% and that of NA about 20% when incubated in the patients' plasma. All these effects seem to be mainly due to norzimelidine. Desipramine produced strong inhibition of the uptake of NA in hypothalamic synaptosomes but weak effect on the 5-HT uptake. Urinary MHPG tended to decrease during desipramine treatment but was not affected or tended to increase during zimelidine treatment.
 ...
PMID:Controlled cross-over study of a 5-HT uptake inhibiting and an NA uptake inhibiting antidepressant. 645 94

A 24-year-old woman with a unipolar depression had an augmented thyroid-stimulating hormone response to thyrotropin-releasing hormone (TRH), suggesting subclinical hypothyroidism. Desipramine produced rapid cycling between depression and hypomania. After discontinuation of the desipramine she was successfully treated with lithium and thyroid hormone replacement. We discuss the possible role of hypothyroidism in the etiology of tricyclic-induced rapid mood cycling, and suggest that the TRH test may help identify depressed patients predisposed to rapid mood cycling on tricyclics. The possibility that such patients respond to lithium and/or thyroid hormone replacement needs to be further investigated.
 ...
PMID:Does subclinical hypothyroidism predispose to tricyclic-induced rapid mood cycles? 680 54

The ability of antidepressant drugs, electroconvulsive treatment (ECT), or lithium chloride (LiCl), to modify prolactin secretion in the rat was studied. Chlorimipramine, citalopram, fluoxetine, imipramine and zimelidine potentiated the low dose 5-hydroxytryptophan (5-HTP)-induced increase in prolactin secretion, suggesting inhibition of serotonin (5-HT) uptake by these drugs. Amitriptyline, doxepin, iprindole, mianserin and trazadone inhibited the prolactin stimulating effects of high doses of 5-HTP and quipazine, suggesting that these drugs have 5-HT receptor blocking properties. Tandamine inhibited only 5-HTP-induced increase in prolactin secretion. Chronic administration of imipramine, potentiated the effect of low dose 5-HTP significantly more than an acute dose. Amitriptyline, produced similar inhibition of the 5-HTP-induced increase in prolactin secretion after both acute and chronic administration. The ability of bupropion and mazindol to inhibit alpha-methylparatyrosine-induced prolactin secretion, and of nomifensine to inhibit reserpine-induced prolactin secretion, is consistent with other evidence that these agents are indirect dopamine (DA) agonists. Desipramine, acutely, had no effect on any of the above paradigms but after chronic administration, potentiated the effect of low dose 5-HTP on prolactin secretion. Nortriptyline had no effect on prolactin secretion after acute or chronic treatment. ECT for 10 days did not affect the ability of a 5-HT agonist or d-amphetamine to modify prolactin secretion. However, chronic, but not acute, treatment with LiCl markedly enhanced the prolactin response to 5-HT agonists and reserpine while shifting the dose response curve for d-amphetamine and apomorphine to the right. These results are discussed in light of current theories of the role of 5-HT and DA in depression.
 ...
PMID:Effect of antidepressants, lithium and electroconvulsive treatment on rat serum prolactin levels. 697 60

A double-blind comparison of doxepin versus desipramine was performed in carefully defined patients with research diagnosis of Primary Affective Disorder. While both drugs showed equal efficacy after 4 weeks, doxepin demonstrated a more rapid onset of action and surprisingly few side effects. Desipramine did not prove to be "activating" and did not worsen agitated depression. Although doxepin showed few autonomic side effects, it was nevertheless sedating, indicating that tricyclics with more anticholinergic effects are not necessarily more sedating drugs.
 ...
PMID:Double-blind comparison of doxepin and desipramine in patients with primary affective disorder. 704 45

Desipramine (DMI), a tricyclic antidepressant drug used in the treatment of depression, has been shown to increase steady-state levels of glucocorticoid receptor type II (GRII) mRNA in vitro and in vivo. To determine whether this effect is secondary to norepinephrine (NE) reuptake inhibition i.e., increases in synaptic NE induced by DMI, GRII mRNA levels were assayed in rat hippocampus following neurotoxic lesioning of NE neurons with DSP4. Chronic DMI treatment significantly increased GRII mRNA levels to the same degree in lesioned and non-lesioned animals. In contrast to DMI, the non-tricyclic antidepressant fluoxetine had no effect on GRII mRNA. These results provide evidence which demonstrates that a tricyclic antidepressant can regulate steady-state mRNA levels in vivo by a mechanism which is independent of its effects on synaptic monoamine levels.
 ...
PMID:Norepinephrine-independent regulation of GRII mRNA in vivo by a tricyclic antidepressant. 758 16

1. Twenty-one patients with post-traumatic stress disorder (PTSD) were included in a study utilizing baseline rapid eye movement (REM) latency measurements, the dexamethasone suppression test (DST), and the protirelin (thyroid releasing hormone; TRH) stimulation test. The DST and TRH stimulation test were repeated after double blind treatment with desipramine. 2. A high number of patients (75%) exhibited a REM latency of 60 min or less and blunted thyroid stimulating hormone (TSH) response to TRH (61.9%) on baseline tests while only one patient showed cortisol escape from dexamethasone suppression. 3. After four weeks of desipramine treatment, significant improvements were reported in the Hamilton Rating Scale for depression, but not for anxiety symptoms, PTSD symptoms, or self-rated depressive symptoms. 4. Desipramine treatment did not affect hormonal responses to TRH. 5. The findings of shortened REM latency and altered TRH stimulation test suggest PTSD and depression may share some pathophysiological abnormalities.
 ...
PMID:REM latency, dexamethasone suppression test, and thyroid releasing hormone stimulation test in posttraumatic stress disorder. 762 94

Thirty-seven patients who fulfilled DSM-III-R criteria for Major Depressive Disorder were recruited for a double-blind controlled trial of Desipramine and placebo for 6 weeks. Data about social cognitive variables, including social adversities, investment in roles and goals, general social support and crisis support were collected. Crisis support had a moderating effect on the initial level of depression: the more crisis support the subjects had, the less depressed they were on recruitment. Initial level of depression, the experience of adversity and drugs all contributed significantly to recovery defined as Hamilton Rating for Depression less than 10 at week 6. When recovery was defined as Hamilton score halved or more than halved between week 2 and week 6, subjects' level of ideal emotional support, and whether they had experienced adversity in their most invested domains, contributed significantly to recovery, independent of any drug effects or the initial level of depression. The higher their level of ideal emotional support, the less was the chance of these subjects recovering. The findings of this study pointed to the importance of controlling for psycho-social variables in studies of response to treatment.
 ...
PMID:The impact of social cognitive variables on the initial level of depression and recovery. 782 67

Desipramine (DMI), a tricyclic antidepressant and norepinephrine (NE) reuptake blocker, is reported to induce ACTH and cortisol release acutely in humans, probably by facilitating central NE neurotransmission. Tricyclic antidepressant therapy, including DMI, normalizes the ACTH and cortisol hypersecretion that often accompanies depression. The mechanism of hypothalamic-pituitary-adrenal (HPA) axis inhibition by DMI in humans is unknown. In rats, DMI reduces the activity of the locus ceruleus, a major source of NE innervation of the hypothalamic paraventricular nucleus, the site of CRH neurons. Naloxone induces ACTH and cortisol release in humans through a noradrenergic-mediated mechanism and a probable consequent stimulation of hypothalamic CRH release. To study the interaction of these drugs on NE neurotransmission and, hence, HPA axis activity in humans, we administered DMI alone and with naloxone in a randomized, double blind, placebo-controlled protocol in eight healthy male volunteers. DMI (75 mg, orally) was given 180 min before naloxone (125 micrograms/kg BW, i.v.). Plasma ACTH and cortisol were measured at frequent intervals from 60 min before to 120 min after naloxone treatment. Plasma cortisol levels were 77% higher 180 min after DMI compared to those after placebo treatment (287 +/- 17 vs. 162 +/- 14 nmol/L; P = 0.000005). DMI reduced the naloxone-induced rise in cortisol (P = 0.02), but there was no change in the integrated cortisol response. The increase in basal plasma ACTH levels after DMI treatment did not reach statistical significance. DMI significantly increased systolic blood pressure and heart rate consistent with an effect on the noradrenergic control of the cardiovascular system. In summary, DMI increased basal cortisol levels consistent with facilitation of NE neurotransmission and, hence, hypothalamic CRH release. However, DMI had no enhancing effect on naloxone-induced cortisol release. This contrasts with the synergy observed when non-antidepressant agents that increase NE neurotransmission are given with naloxone to humans. DMI increases glucocorticoid feedback sensitivity in the rat HPA axis after several weeks through up-regulation of central corticosteroid receptors. However, this slowly developing effect is unlikely to occur during these acute studies. The effect of DMI on naloxone-induced cortisol release is consistent with an inhibitory effect on central noradrenergic control of ACTH release, perhaps at the locus ceruleus. This is the first human study to suggest an inhibitory effect of DMI on central noradrenergic control of ACTH release.
 ...
PMID:The effect of desipramine on basal and naloxone-stimulated cortisol secretion in humans: interaction of two drugs acting on noradrenergic control of adrenocorticotropin secretion. 788 33

In the olfactory-bulbectomised rat model of depression, neutrophil phagocytosis was significantly decreased and phagocytosis started later in comparison to sham-operated animals. Both desipramine and lithium chloride treatment significantly reversed the depressed neutrophil phagocytosis and shortened the time to commencement of phagocytosis in drug-treated bulbectomised rats. The catalase and glutathione peroxidase (GSH-PX) activities in bulbectomised rats were decreased, while superoxide dismutase (SOD) was significantly increased. Chronic desipramine and lithium chloride treatment slightly improved catalase activity in the bulbectomised rats. Desipramine significantly reversed the reduction in activity of GSH-PX, but failed to reverse the increased activity of SOD. In contrast, lithium chloride significantly reversed SOD activity to normal values, without affecting GSH-PX activity in the bulbectomised rats.
 ...
PMID:Catalase, superoxide dismutase and glutathione peroxidase activity in neutrophils of sham-operated and olfactory-bulbectomised rats following chronic treatment with desipramine and lithium chloride. 796 55

Wistar Kyoto (WKY) rats, as compared to several other rat strains, are hypoactive in the open field test and in the defensive burying test. WKY rats readily acquire a learned helplessness task as well as a passive avoidance tasks. WKY rats also reveal a greater susceptibility to restraint-induced stress ulcer. The behavioral tests suggest the presence of depressive behavior in WKY rats. When exposed to the Porsolt forced-swim test of 'behavioral despair', WKY rats are judged as exhibiting more depressive behavior. Desipramine not only reduced immobility in the forced-swim test, but also diminished the severity of restraint-induced stress ulcer. These data suggested a heightened activity of the hypothalamic-pituitary axis. Basal plasma ACTH levels did not differ between WKY rats and Wistar rats, but serial plasma ACTH response to restraint stress was significantly greater for WKY rats. These data suggest that depressive behavior is a characteristic of WKY rats and this strain is a valuable model for studying depression which may be induced by an exaggerated stress response.
 ...
PMID:Depressive behavior and stress ulcer in Wistar Kyoto rats. 813 89


<< Previous 1 2 3 4 5 6 7 8 Next >>