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)

The symptom of carbohydrate craving and increased appetite (CHH) was studied in 180 outpatients receiving antidepressant treatment. One hundred and fifty-eight of these patients had a DSM-III diagnosis of panic disorder and 17, major depression. The incidence of CHH was similar in both diagnostic groups. Thus, antidepressant treatment is associated with CHH in patients with diagnoses, other than depression. Desipramine was least likely to induce CHH compared to imipramine, amitriptyline and doxepin. Most patients who developed CHH on imipramine no longer experienced this side effect when switched to desipramine. CHH was not more frequent among women and not associated with antidepressant dosage or treatment response. Histamine H-1 receptor blockade may be an important factor in the etiology of CHH.
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PMID:Carbohydrate craving and increased appetite associated with antidepressant therapy. 319 15

Recently detoxified men with alcohol dependence (n = 15) and healthy volunteers (n = 14) were administered oral and intravenous imipramine and desipramine. Alcoholics had significantly greater total body clearance of imipramine (0.93 vs. 0.48 L/hr/kg; P less than 0.05) and desipramine (1.00 vs. 0.62 L/hr/kg; P less than 0.05) than did control subjects. Intrinsic clearance of unbound imipramine was greater in the alcoholic group (19.80 vs. 6.56 L/hr/kg; P less than 0.05), as was the intrinsic clearance of unbound desipramine (14.52 vs. 9.05 L/hr/kg; P less than 0.05). The mean elimination half-life for imipramine was significantly decreased in alcoholics (8.7 vs. 19.9 hours after intravenous infusion and 10.9 vs. 19.6 hours after oral administration; P less than 0.05). The mean elimination half-life for desipramine was decreased in alcoholics after intravenous infusion (16.5 vs. 22.4 hours; P less than 0.05). Unbound fractions of drug in plasma were decreased in the alcoholic group for both imipramine and desipramine after both routes of administration. alpha 1-Acid glycoprotein levels were elevated in the alcoholic group whereas total protein and albumin levels did not differ between groups. These findings suggest that recently detoxified alcoholics may require higher doses of imipramine than do nonalcoholic subjects. Desipramine clearance was affected to a lesser degree than imipramine, suggesting that from a pharmacokinetic standpoint it may be the preferred drug for the treatment of alcoholics with depression. Periodic monitoring of plasma levels may be required for recently abstinent alcoholics treated with antidepressants.
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PMID:Clinical pharmacokinetics of imipramine and desipramine in alcoholics and normal volunteers. 336 15

A theory of excessive transmission of serotonin (5-HT) in depression has been previously proposed. The purpose of the present study was to test this theory further by using the model of depression in rats induced by L-5-hydroxytryptophan (5-HTP), the precursor of 5-HT. The drug effects on 5-HTP (25 mg/kg) induced behavioral depression were tested by chronic administration using methysergide which is a postsynaptic blocker of 5-HT, or by comparable clinical doses of antidepressant drugs. Methysergide (2 mg/kg) blocked 5-HTP induced depression on days 8 and 22 after initiation of medication by 70% and 83%, respectively. Among antidepressants, mianserin (2 mg/kg) was the first to produce an effect, displaying a 38% effect as early as 1 day after the start of medication and having blocking effects of 52% and 72% on days 8 and 22. Desipramine (5 mg/kg), doxepine (5 mg/kg), imipramine (5 mg/kg) and trazodone (10 mg/kg) showed no significant effect on days 1 and 8, and on day 22, 64, 36, 33 and 32% blocking, respectively. Amitriptyline had an initial effect of 41% at a dose of 10 mg/kg. Clomipramine (5 mg/kg), zimelidine (6 mg/kg) and chlorpromazine (2.5 mg/kg), which is a neuroleptic, showed no effect. Considering these results in light of recent data reported on the 5-HT synapse, it was suggested that 5-HTP induced depression may be induced by excessive transmission of 5-HT and that some antidepressant drugs may produce their effect by blocking this postsynaptic transmission. Based on these results, the mechanisms of human depression were discussed.
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PMID:Action of chronically administered antidepressants on the serotonergic postsynapse in a model of depression. 349 69

Desipramine, a tricyclic antidepressant, inhibits the neuronal uptake of adrenaline and noradrenaline and, as a radioligand, labels the noradrenaline transporter in central and peripheral tissues of the rat. To study whether [3H]desipramine also labels the neuronal adrenaline transporter in vitro, its binding was evaluated in the frog heart, a tissue with a rich adrenergic innervation but virtually devoid of noradrenergic innervation. [3H]Desipramine binding to membranes from the frog heart was of high affinity (Kd = 1.94 nM) and was potently inhibited by nisoxetine and (+)oxaprotiline. Unexpectedly, [3H]desipramine binding to the transporter for adrenaline in the frog heart was also sensitive to inhibition by imipramine and the atypical antidepressants mianserin and iprindol. This is the first study to demonstrate radioligand binding to the neuronal transporter for adrenaline. The results indicate that the pharmacological profile of the transporter for adrenaline may be different from that of the noradrenergic transporter, if species differences can be excluded. It remains to be established if the affinity of imipramine, mianserin and iprindol for the adrenaline transporter contributes to their therapeutic efficacy in depression.
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PMID:[3H]desipramine labels with high affinity the neuronal transporter for adrenaline in the frog heart. 349 46

Antidepressant treatment trials of irritable bowel syndrome (IBS) have suggested beneficial effects. Twenty-eight patients with the disorder (9 constipation-predominant, 19 diarrhea-predominant) completed a double-blind crossover study using desipramine, atropine, and placebo in random sequence. A four-week observation period preceded three six-week test periods. Bowel habits, abdominal distress, and affect were reported daily and in biweekly evaluations. Psychological assessments and rectosigmoid contractile studies were done in each period. Stool frequency, diarrhea, abdominal pain, depression, and slow contractions decreased significantly more in diarrhea-predominant patients during desipramine compared with placebo and atropine treatments. Diarrhea-prone patients' depression scores fell more in all periods than constipation-prone patients. Fifteen patients (13 diarrhea-predominant) improved globally during desipramine, five during placebo and six during atropine treatments. Desipramine may be helpful in treating IBS, perhaps through antidepressant and antimuscarinic effects.
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PMID:Effects of desipramine on irritable bowel syndrome compared with atropine and placebo. 354 19

Decreased ventilatory responses to carbon dioxide (CO2) correlate with elevated scores on tests for depression in normal subjects and with episodes of endogenous depression in psychiatric patients. Patients with severe chronic obstructive pulmonary disease (COPD) frequently develop resting hypercapnia due to impaired ventilatory mechanics or drive, and may also have elevated scores on tests for depression. Tricyclic antidepressant drugs can improve ventilatory mechanics and possibly drive. We hypothesized that antidepressant drugs might enhance ventilatory drive and improve arterial blood gases in patients with severe COPD and that these improvements might correlate with improvement in depression scores. Therefore, we studied the effects of desipramine versus placebo on spirometry, resting arterial blood gases, hypercapnic ventilatory and mouth occlusion pressure responses, and scores on the Beck and Zung self-rated depression scales. In our patients the resting arterial CO2 (PaCO2) was found to depend almost equally on ventilatory mechanics and drive. In addition, patients with higher depression scores tended to have a lower PaCO2 when the severity of airways obstruction was taken into consideration. In a 16-week, double-blind, crossover comparison of desipramine with placebo, both treatments led to significant improvement in depression scores. Desipramine had no effects on resting PaCO2, spirometry, or ventilatory control.
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PMID:Effect of desipramine on control of ventilation and depression scores in patients with severe chronic obstructive pulmonary disease. 392 77

The atypical neuroleptic sulpiride is also prescribed for depression because of its activating effect. However, such an effect does not necessarily imply an action identical to that of classical antidepressants, and a laboratory comparison of the neuroleptic and antidepressant activities of sulpiride may contribute to a better definition of its psychotherapeutic profile. Sulpiride isomers were studied in the rat in four behavioural models of depression which are thought to be influenced by neuroleptics in different ways. Desipramine (imipramine) and haloperidol were employed in each test as a standard antidepressant and neuroleptic, respectively. The four tests were: 1) prevention of apomorphine-induced sedation: 2) antagonism of apomorphine-induced hypothermia; 3) behavioural despair (swim test); 4) learned helplessness ( FR2 lever pressing escape). Desipramine ameliorated behaviour in all tests; haloperidol ameliorated the response to test 1, influenced that to test 2 in a neuroleptic-like way and worsened the responses to tests 3 and 4. (-)-Sulpiride worked in a similar way to haloperidol in all tests. (+)-Sulpiride significantly and dose-dependently ameliorated the responses to test 3 and was inactive in the others. No conclusion was drawn from test 1 owing to its lack of specificity; the results of the remaining tests indicated a neuroleptic profile of (-)-sulpiride and suggested a potential "antidepressant" activity of (+)-sulpiride which merits further investigation.
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PMID:Antidepressant versus neuroleptic activities of sulpiride isomers on four animal models of depression. 614 54

Several weeks of tricyclic antidepressant administration are required to effectively reverse depression. To determine whether there are adaptive changes in andrenergic nerve function which correspond to the clinical onset of antidepressant action, the endogenous norepinephrine content, [3H]norepinephrine uptake and retention, responses to exogenous norepinephrine and the release of norepinephrine during field stimulation were studied using left atrial strips isolated from rats treated with either acutely or chronically with tricyclic antidepressants. Desipramine, nortriptyline, chlorimipramine and iprindole were administered to rats, 10 mg/kg i.p., twice daily. After 14 days of drug administration, the responses to field stimulation were potentiated markedly by all four tricyclics. In contrast, 1 day of tricyclic treatment had only slight potentiating effects. When phenoxybenzamine, 10(-7) M, was added to the organ bath in order to block the inhibitory presynaptic alpha receptor, the responses of control atria and atria from rats treated for 1 day with desipramine were potentiated but those of atria treated for 21 days with desipramine were not potentiated. The development of presynaptic alpha receptor subsensitivity during chronic tricyclic administration would explain these findings. Other possible explanations were also investigated. The uptake and retention of [3H]norepinephrine was markedly inhibited to a similar degree of either 1 or 14 days of desipramine or nortriptyline administration. One day of chlorimipramine treatment decreased the amount of [3H]norepinephrine taken up and retained by left atrial strips, and after 14 days of treatment decreased the amount further. In contrast, neither 1 nor 14 days of iprindole administration had any effect on the uptake and retention of [3H]norepinephrine. These data indicate that the potentiation of the responses to field stimulation cannot be explained by the inhibition of norepinephrine uptake. The inotropic response to exogenous norepinephrine was not altered by any duration of administration of any of the four tricyclics studied. Furthermore, the endogenous norepinephrine content of atria did not change after as many as 21 days of desipramine administration. The present results indicate that the potentiation of the effects of adrenergic nerve transmission during chronic tricyclic administration is the result of an increase in norepinephrine release which occurs due to the development of presynaptic alpha receptor subsensitivity. The time course of development of presynaptic receptor subsensitivity corresponds well with the onset of clinical activity of these drugs.
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PMID:Potentiation of responses to adrenergic nerve stimulation in isolated rat atria during chronic tricyclic antidepressant administration. 625 16

(3H)Imipramine binding sites in the brain are localized mainly on serotonergic nerve terminals. In the hippocampus of rats with a lesion of serotonergic nerve terminals produced by neonatal administration of 5,7-DHT, the depletion of serotonin was paralleled by a decrease in (3H)imipramine recognition sites. (3H)Imipramine recognition sites in brain tissue or platelets are associated with serotonin uptake sites. A significant correlation exists between the potency of a series of antidepressants and other compounds to displace high affinity (3H)imipramine binding and to inhibit the neuronal uptake of serotonin but not of norepinephrine. There is a significant correlation between the ability of drugs to displace (3H)desipramine binding and to inhibit norepinephrine but not serotonin reuptake. (3H)Desipramine recognition sites are located, at least in part, at noradrenergic nerve terminals since destruction of these terminals by 6-OH-DA results in parallel decrease in (3H)desipramine, but not in (3H)imipramine binding. The high affinity recognition sites of (3H)imipramine and (3H)desipramine in the brain could be physiologically and pharmacologically relevant regulatory sites associated with neuronal uptake of serotonin and norepinephrine, respectively. Treatments which clinically lead to improvement of depression (eg. antidepressants, ECT, REM sleep deprivation) were shown to "down-regulate" (3H)imipramine binding sites in brain of experimental animals. The density of (3H)imipramine binding sites was shown to be lower in platelets from depressive patients and in brains of suicide victims. It appears that decreased binding of (3H)imipramine to platelets of depressed patients is a promising biological marker of depression, although there is no conclusive evidence to indicate whether it is a state- or trait-dependent phenomenon.
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PMID:Antidepressant binding: implications for the mode of action and the biology of depression. 632 Feb 97

Marginal differences in adverse effects become the basis of selection among equally effective drugs, especially in outpatient treatment. Desipramine's side effect profile makes it a particularly acceptable drug for the outpatient treatment of depression or depression with panic attacks. Relevant aspects of desipramine's pharmacologic properties and of prescribing practices are reviewed.
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PMID:Treatment of outpatients with desipramine. 638 6


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