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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the study was to quantitatively compare the relative affinities of noradrenaline, adrenaline, dopamine and isoprenaline for the, probably neural, receptors mediating feedback control of sympathetic neurotransmitter secretion. The experiments were carried out in isolated superfused field stimulated guinea-pig vas deferens, in which the noradrenaline stores had been labelled by preincubation with tritiated (-)-noradrenaline. Desipramine and normetanephrine were added to prevent rebinding of transmitter. Exogenous noradrenaline was found to cause a dose-dependent and reversible depression of the secretion of tracer noradrenaline evoked by field stimulation. Since the depressing effect was not affected by a ten-fold rise in the desipramine concentration, it seems likely that it was not due to uptake and preferential secretion of unlabelled exogenous noradrenaline, but was truly due to depression of the secretory mechanism. Adrenaline was significantly more potent than noradrenaline, as inhibitor of the secretion of tracer transmitter, while dopamine, at the same molar concentration, was without effect. The beta-agonist isoprenaline did not depress, but rather tended to enhance, the secretion of tracer noradrenaline. It is concluded that the receptors controlling the secretion of noradrenaline from the sympathetic nerves of guinea-pig vas deferens quantitatively-with regard to sensitivity-as well as qualitatively-with regard to order of preference for different catecholamines-resemble the "classical" alpha-receptors of e.g. smooth muscle in the same tissue.
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PMID:Selectivity for catecholamines of presynaptic alpha-receptors involved in feedback control of sympathetic neurotransmitter secretion in guinea-pig vas deferens. 24 Jan 32

1 Stereotaxic lesioning and microiontophoretic techniques were used to study the effects of lesions of the medial forebrain bundle (MFB) on the potentiation by antidepressant drugs of responses to monoamines of cortical neurones.2 Active uptake of noradrenaline (NA) and 5 hydroxytryptamine (5-HT) by synaptosomes from the motor and somatosensory cortex was reduced to approximately 20%, 10 to 14 days following lesion of the MFB in rats.3 Unilateral lesions of the MFB caused changes in responsiveness of neurones to NA and 5-HT, applied by iontophoresis, in the cortex ipsilateral to the lesion. Excitatory responses to both amines were observed less frequently and depression was the predominant response. Excitatory responses on the lesioned side were significantly smaller than on the unlesioned side, but the size of depressant responses was unaltered.4 Viloxazine strongly potentiated responses of cortical neurones to NA and 5-HT on both sides of the brain of MFB-lesioned rats. There were no significant differences in the potentiation of responses to monoamines on the lesioned or unlesioned sides of the brain.5 Desipramine potentiated responses to NA of neurones in the cortex ipsilateral to MFB lesions.6 Chlorimipramine potentiated responses to 5-HT of neurones in the cortex ipsilateral to MFB lesions.7 It is concluded that antidepressants can potentiate responses to monoamines despite a profound reduction in presynaptic terminals. The potentiation is unlikely to be the result of blockade of monoamine uptake into presynaptic terminals, and is probably a postsynaptic effect of the antidepressant drugs.
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PMID:Potentiation of responses to monoamines by antidepressants after destruction of monoamine afferents. 31 65

The results of a double blind trial of Viloxazine and Desipramine in 30 hospitalized depressives are reported. Hamilton's Rating Scale for Depression was the outcome criterion. No statistically significant differences were found between drugs in efficacy and onset of action. Patients on either drug showed a significant reduction in symptoms after one week of treatment and at the end of the trial. Side effects reported with Viloxazine were predominantly nausea and dizziness of a transient nature. Patients on Desipramine reported the usual side effects associated with antidepressant use and two of them had to be withdrawn from the trial because of an allergic rash. Laboratory values and EKG tracings did not show any trend of abnormalities. It is concluded that Viloxazine is an effective and safe antidepressive drug and seems to be particularly indicated in geriatric and cardiovascular patients with a concomitant depression.
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PMID:[Double-blind trial of 2 antidepressive drugs]. 34 50

Only a few of the eight tricyclic antidepressants available today have been studied systematically in the elderly. Tertiary amine tricyclics such as amitriptyline and imipramine have been reported to be effective in depressed geriatric patients, but because of their potential for side effects, it is not advisable to use them in the elderly. Desipramine has a less toxic side effect profile, especially with respect to anticholinergic effects, but its efficacy has not been well studied. This does not mean, however, that it is not an effective drug for the elderly depressed. Nortriptyline is the tricyclic that has been the most studied. The results of those studies show that it should be recommended as an antidepressant for older patients. It is effective in both the acute and continuation treatment of depression in the elderly. As far as its use in maintenance treatment, the results are mixed but at this moment there is nothing with which to compare it. It has a favorable side effect profile: low anticholinergic activity; relatively few cardiac side effects, even in patients with preexisting cardiac disease; and relatively less orthostatic hypotension. Nortriptyline also has the virtue of an established therapeutic range for its steady-state plasma level. The role of its 10-hydroxy metabolite needs to be further explored, but when its contribution to efficacy and toxicity is better understood, it may be possible to use nortriptyline in a more precise and safe way in elderly patients. The bulk of evidence suggests, partly by default, that nortriptyline should probably the tricyclic-of-first-choice in treating an elderly patient with major depression.
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PMID:Using tricyclic antidepressants in the elderly. 160 Apr 82

Platelet adrenergic receptor binding has been studied by several groups of investigators as a possible marker for depression and other psychiatric conditions. Although some of the findings have been discrepant, the results of the majority of studies that have used imidazoline compounds as ligands have confirmed elevated alpha 2-adrenergic receptor binding in depression. We have emphasized the advantages of obtaining platelet-purified plasma membranes and using tritiated para-aminoclonidine as the ligand of choice. By using "site-selective" concentrations of tritiated para-aminoclonidine, we have identified two high-affinity-binding sites of the platelet alpha 2-adrenergic receptor that appear to be upregulated in depression before treatment. Depressed patients were treated with desipramine hydrochloride for 6 to 8 weeks, and platelet binding was reassessed. Desipramine reduced binding to nearly normal levels at both site-selective concentrations of tritiated para-aminoclonidine. The concentrations of plasma catecholamines could play a role in the downregulation of binding at posttreatment. We discuss these findings in the context of platelet imidazoline-binding sites being a possible state-dependent marker for depression.
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PMID:Desipramine lowers tritiated para-aminoclonidine binding in platelets of depressed patients. 168 92

In pontine slices of the rat brain, the frequency of spontaneous action potentials of locus coeruleus (LC) neurones was recorded extracellularly. Noradrenaline 0.1-100 mumol/l, UK 14,304 0.01-100 nmol/l, [Met5]-enkephalin 1-10,000 nmol/l and [D-Ala2,D-Leu5]enkephalin 0.1-1,000 nmol/l, all depressed the firing rate. Rauwolscine 1 mumol/l antagonized the effects of both noradrenaline and UK 14,304, but potentiated the effects of [Met5]enkephalin and [D-Ala2, D-Leu5]enkephalin. Idazoxan 1 mumol/l acted in a similar manner. Prazosin 1 mumol/l did not change the effects of either noradrenaline or [Met5]enkephalin. Naloxone 0.1 mumol/l antagonized both [Met5]enkephalin and [D-Ala2, D-Leu5]enkephalin, but failed to alter the effects of either noradrenaline or UK 14,304. Rauwolscine, idazoxan and prazosin, all 1 mumol/l, as well as naloxone 0.1 mumol/l, did not influence the firing rate when given alone. Desipramine 1 mumol/l inhibited the discharge of action potentials in a rauwolscine-antagonizable manner. Noradrenaline 10 mumol/l produced the same depression of firing, both in the presence of noradrenaline 1 mumol/l and [Met5]enkephalin 0.03 mumol/l. Likewise, the effect of [Met5]enkephalin 0.3 mumol/l was the same, irrespective of whether it was added to a medium containing [Met5]enkephalin 0.03 mumol/l or noradrenaline 1 mumol/l. The spontaneous activity of LC neurones is inhibited by somatic alpha 2-adrenoceptors and opioid mu-receptors. We suggest that the two receptors interact with each other at a site located between themselves and not in the subsequent common signal transduction system.
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PMID:Blockade of alpha 2-adrenoceptors increases opioid mu-receptor-mediated inhibition of the firing rate of rat locus coeruleus neurones. 198 56

Prompted by a recent study suggesting that the combination of desipramine hydrochloride and fluoxetine down-regulates beta-adrenergic receptors more rapidly than either drug alone, we administered both desipramine and fluoxetine to 14 inpatients with major depression in an open, 4-week trial. Desipramine plasma levels drawn 24 hours after an initial standardized dose were used to rapidly adjust desipramine dosage and compensate for the interactive effects of fluoxetine on desipramine levels in the blood. Responses were retrospectively compared with those of 52 inpatients who were descriptively similar and previously treated in the same setting with desipramine alone. Response was significantly more rapid in the group that received both drugs. One week after treatment began, the mean change in Hamilton Depression Rating Scale scores was 42% in the group that received both drugs and 20% in the group that received desipramine alone (Mann-Whitney U test, P = .007). Two weeks after administration of the drugs, the mean change in scores of the group that received both drugs was 60%, while a 30% change was noted in the patients treated with desipramine alone (P = .001). Ten (71%) of the 14 patients in the group that received both drugs completely remitted (change in Hamilton Depression Rating Scale score of greater than 75%, and final score of less than 7) within 4 weeks, while few patients treated with desipramine alone met these criteria within 4 weeks. This preliminary study suggests that treatment with both desipramine and fluoxetine is a rapid and effective strategy for treatment of major depression, and supports recent hypotheses of noradrenergic-serotonergic synergism.
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PMID:A preliminary, open study of the combination of fluoxetine and desipramine for rapid treatment of major depression. 151 82

Seasonal affective disorders (SADs) are disturbances of mood bearing a fixed relationship to season. Wintertime depression is the most widely accepted form of SAD. Full-spectrum, bright artificial light is the standard treatment for this syndrome. Tranylcypromine was effective in the treatment of 14 patients meeting both the National Institute of Mental Health and DSM-III-R criteria for winter depression. The average patient experienced a 91 percent reduction in depressive symptoms within 3 to 4 weeks of the initiation of this treatment. Desipramine initially appeared to be an effective treatment for winter depression. Eight patients started treatment with desipramine in October or November. One patient was unresponsive, and 8 patients appeared to be responsive but relapsed in the following 2 to 4 months. Twenty-five patients were subsequently treated with bupropion. One patient was unresponsive to bupropion, but the others experienced a substantial reduction in symptoms. Chronobiologic properties that might explain or predict the effectiveness of drugs used to treat winter depression are discussed.
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PMID:Pharmacological responsiveness of winter depression. 212 35

Desipramine has the least anticholinergic and sedative effects of the first generation tricyclic antidepressant agents, but its pain-relieving potential has received little study. Other antidepressant agents--notably amitriptyline--are known to ameliorate postherpetic neuralgia, but those agents are often toxic. In a randomized double-blind crossover design, we gave 26 postherpetic neuralgia patients 6 weeks of treatment with desipramine (mean dose, 167 mg/day) and placebo. Nineteen patients completed both treatments; 12 reported at least moderate relief with desipramine and two reported relief with placebo. Pain relief with desipramine was statistically significant from weeks 3 to 6. Psychiatric interview at entry into the study produced a diagnosis of depression for 4 patients; pain relief was similar in depressed and nondepressed patients and was statistically significant in the nondepressed group alone. We conclude that desipramine administration relieves postherpetic neuralgia and that pain relief is not mediated by mood elevation. Blockade of norepinephrine reuptake, an action shared by desipramine, amitriptyline, and other antidepressant agents that have relieved neuropathic pain, may be involved in relief of postherpetic neuralgia.
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PMID:Desipramine relieves postherpetic neuralgia. 217 51

The authors analyzed the relative contributions of improvement in depressive and anxiety symptoms, as measured by the Hamilton Rating Scale for Depression (HRSD) and the Hamilton Rating Scale for Anxiety (HRSA), respectively, after 1 week of treatment to the prediction of improvement in HRSD score after 6 weeks of antidepressant pharmacotherapy. Fifty-six subjects completed 6 weeks of treatment with either desipramine (n = 20), alprazolam (n = 18), or a desipramine-alprazolam combination (n = 18). The results showed that early improvement in the HRSD was a moderately strong predictor of the total 6-week improvement in HRSD score, and a better predictor than early improvement in the HRSA. Partial correlations showed that early HRSD improvement was significantly related to total HRSD improvement within the alprazolam group. This pattern of response differed from those observed for the other treatment groups. Desipramine-treated subjects showed gradual improvement over the course of the study, and the improvement in week 1 was not so strongly predictive of overall improvement. The relationship between early and total HRSD improvement for the combination treatment group was intermediate to the other two groups. These findings are discussed in the context of the relationship between depression and anxiety, and potential implications for the treatment of these overlapping and often mixed syndromes.
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PMID:Antidepressant or antianxiety? A study of the efficacy of antidepressant medication. 219 76


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