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PubMed1993

Seven-day variable-stress regime alters cortical beta-adrenoceptor binding and immunologic responses: reversal by imipramine.

Rats were submitted daily to a variable stressor for 1 week with or without concurrent imipramine (IMI) administration. One day after the last injection or stressful event, binding of cortical beta-adrenoceptors was determined in all experimental groups. Another group of chronically stressed animals with or without concurrent IMI administration were sacrificed 24 h following the last stress or injection treatment, and several immunologic parameters were evaluated. Chronically stressed rats showed an enhanced number of cortical beta-adrenergic sites without changes in their affinity. This effect was not present following concurrent administration with the antidepressant. In addition, a decreased percentage of T lymphocytes and a reduced delayed-type hypersensitivity reaction was also observed in stressed animals. Both responses were no longer evident when stressed rats were previously administered IMI. A possible link between behavioral, neurochemical, and immunologic alterations due to the stress regime is discussed.

Animals↗
PubMed1995

Crucial role of D1 dopamine receptors in mediating the antidepressant effect of imipramine.

Although the neurochemical effects of chronic imipramine (IMI) treatment have been related to an increased adrenergic as well as dopaminergic transmission, no clear-cut evidence exists on whether one of these two neuronal systems mediates the behavioral effects of the tricyclic compound. Because a large body of evidence favors the role of dopamine, the interference of a selective inhibition of D1 or D2/D3 dopamine receptors on IMI effect upon the learned helplessness behavior (LH) in rats was studied. A 2-week treatment with SCH 23390, followed by a 24-h washout, showed almost the same efficacy as chronic IMI in preventing LH induction. Moreover, SCH 23390 given acutely before the pretest completely antagonized the effect of chronic IMI. Furthermore, SKF 38393 administered to drug-naive animals prior to the unavoidable shocks completely neutralized its behavioral sequelae. Finally, the inhibition of D2/D3 dopamine receptors by acute sulpiride did not modify IMI efficacy. These results strongly suggest that D1 dopamine receptor function controls the reactivity of animals exposed to a prolonged unavoidable stress, and mediates IMI antidepressant effect.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1983

Distal colon motility as a predictor of antidepressant response to fenfluramine, imipramine and clomipramine.

The present study gathers results obtained in the treatment of 86 depressed outpatients. The patients were grouped according to their distal colon tone, low-IT and high-IT. All the patients fulfilled the Research Diagnostic Criteria for nonpsychotic unipolar major depressive disorder and were rated on a slightly modified 18-item Hamilton Rating Scale for Depression (HRS). They also completed the 21-item self-rating Beck Depression Inventory (BDI). The 46 subjects from the high-IT group and the 40 subjects from the low-IT group were divided into three subgroups each for double-blind trials performed with clomipramine (CMI), imipramine (IMI), and fenfluramine (FENF). Normalization of HRS and BDI scores and reduction of IT were obtained with IMI and FENF but not CMI in high-IT patients; whereas normalization of both scores and increase in IT were obtained with CMI but not with IMI or FENF in low-IT patients. FENF was not tolerated in this last group. HRS and BDI scores correlated well during in-treatment periods. Our results suggest that distal colon tone is a guide to determining the pharmacotherapy in the depressive disorders. Furthermore, it was shown that FENF is a useful anti-depressant drug in one type of patient.

Adolescent↗
PubMed1985

Cerebrospinal fluid levels of amitriptyline, nortriptyline, imipramine and desmethylimipramine. Relationship to plasma levels and treatment outcome.

Fifty-five (55) depressed patients were treated with amitriptyline (AMI) or imipramine (IMI). Concentrations of AMI, IMI, and their metabolites, nortriptyline (NT) and desmethylimipramine (DMI), were measured in cerebrospinal fluid (CSF) and plasma at steady state by gas chromatography mass spectrometry (GC/MS). Highly significant correlations between CSF and plasma levels of AMI, NT, IMI, and DMI were found (r greater than 0.75; P less than 0.0001 in all cases). There were no significant sex, diagnostic subgroup, or geographic difference in any of the drug parameters measured. An evaluation of the relationship between CSF levels of drug variables and clinical response showed essentially no significant correlations between these various parameters. The results obtained do not support the concept of a 'therapeutic window' for levels of plasma NT in AMI-treated patients. Furthermore, the highly significant correlations between CSF and plasma compartments in terms of drug and metabolite levels would argue against the need to measure CSF levels of these parameters in clinical practice. Plasma level measurements should be equally informative, and simpler to obtain.

Amitriptyline↗
PubMedDate not supplied

Imipramine metabolism in recurrent depressive episodes.

The long-term maintenance of major affective disorders with tricyclic antidepressants is of obvious interest. However, discrete predictors identifying subgroups 'at-risk' for higher recurrence rates have infrequently been cited. The clinical course of 32 major recurrent depressive patients was monitored over 2 years. Analysis of the total tricyclic concentration and the parent: desmethylated ratio revealed that those subjects in a depressive recurrence previously had had a lower imipramine: desipramine ratio (despite matched dosing and nonsignificant total plasma concentrations) than nonrecurrents. Several hypotheses are discussed.

Adult↗
PubMedDate not supplied

Tritiated imipramine binding sites in affective disorders and schizophrenia. Influence of circannual variation.

We have investigated platelet [3H]imipramine binding in normal controls and patients with primary endogenous depression (unipolar and bipolar) or schizophrenia. Absolute Bmax values did not differ between subgroups. However, when circannual variation of binding was taken into account by expressing results as percentages of normalised values derived from the multiple linear regression of Bmax values as a function of time of sampling, schizophrenic patients were found to have higher Bmax than normal controls. There was no significant difference between depressed patients and controls, nor between patients exhibiting plasma cortisol suppression and non-suppression after the dexamethasone suppression test. A significant negative correlation was found between relative Bmax values and cerebrospinal 5-HIAA levels in depressed patients.

Binding Sites↗
PubMedDate not supplied

Dieting and weight loss in volunteers increases the number of alpha 2-adrenoceptors and 5-HT receptors on blood platelets without effect on [3H]imipramine binding.

Platelet monoamine receptor binding was determined in normal male and female subjects before and at the end of a 2- to 3-week weight reducing diet (1200 kcal daily). Dieting was associated with an increase in platelet binding sites for both [3H]yohimbine and [125I]iodolysergic acid diethylamide (iodoLSD). The affinity at the platelet [125I]iodoLSD binding site was reduced. In contrast, [3H]imipramine binding was unchanged. These results have important implications for studies that employ platelet binding as a peripheral marker of neurotransmitter function in psychiatric illness.

Adult↗
PubMedDate not supplied

Platelet 3H-imipramine binding sites in depressed patients and healthy controls: a comparison between morning and afternoon samples.

Platelet 3H-imipramine binding was compared between 19 hospitalized, depressed patients and age-matched controls (n = 11). For each individual person blood samples were withdrawn at 8 a.m. and 3 p.m. on two separate occasions (day 0 and day 28). Mean Bmax and Kd values did not differ between depressed patients and healthy controls at any of the four time-points tested, and no significant differences could be established between the different time-points, though there were irregular intraindividual variations.

Adult↗
PubMedDate not supplied

Phototherapy increases platelet 3H-imipramine binding in patients with winter depression.

The density of platelet 3H-imipramine binding sites (Bmax) was investigated in seven inpatients with winter depression before and after incandescent light treatment and in seven healthy volunteers within a 7-day interval without light exposure. A significantly lower mean Bmax value was found in the depressed patients compared to the controls. After light treatment, parallel to a marked clinical improvement, Bmax increased in each patient and reached or even exceeded the mean values of the controls. These results indicate that in patients with winter depression the decreased Bmax value is state-dependent. The incandescent light treatment has beneficial effect in winter depressives and can influence Bmax values.

Adult↗
PubMed1990

Imipramine and weight gain during the treatment of recurrent depression.

Weight change was examined in 128 depressed outpatients treated successfully with an average dose of 215 mg imipramine and then continued on that treatment regimen for 5 additional months, an average duration of over 33 weeks. More than half the patients experienced a change in weight of 5% or less and only 13.3% experienced a gain of greater than 10%. While males and females did not differ in their pattern of change during acute treatment, females experienced a greater percent change (P less than 0.06) and change in body mass index (P = 0.05) during continuation treatment. The clinical implications of these findings are discussed, especially with respect to the extreme group.

Adult↗
PubMed1991

Effect of phototherapy on 3H-imipramine binding sites in patients with SAD, non-SAD and in healthy controls.

The effect of incandescent light treatment on the density of 3H-imipramine binding sites (Bmax) was investigated in 17 patients with seasonal affective disorder, in eight patients with non-seasonal depression and in six healthy volunteers. A significant increase in mean Bmax value parallel to a marked improvement of the depressive symptoms was found only in patients with SAD. No effect was observed either on mean Bmax value or on clinical symptoms in patients with non-SAD and on mean Bmax value in healthy volunteers.

Adult↗
PubMed1992

Imipramine and weight gain during the long-term treatment of recurrent depression.

The recently completed long-term maintenance trial of full-dose imipramine for recurrent unipolar disorder provided an opportunity to examine the extent to which such doses (200-300 mg daily) are associated with persistent and adverse side effects, particularly weight change. In 115 patients we monitored weight change during the three-year maintenance treatment phase to the point of trial completion, recurrence or termination. No differences were noted between individuals receiving active medication (average gain of 5.8 lbs. during an average treatment period of 725 days) versus those randomized to the 'no-drug' cells (average gain of 2.8 lbs. during an average treatment period of 422 days). Numerous other factors such as body mass index, previous weight gain and gender did not play a differential role in establishing why some individuals gained weight during long-term treatment of depression regardless of specific treatment.

Adult↗
PubMed1994

The pattern of physical symptom changes in major depressive disorder following treatment with amitriptyline or imipramine.

The study describes a sequential analysis of depression-related physical symptoms and their relationship to imipramine and amitriptyline plasma levels over 4 weeks of treatment in 79 unipolar and bipolar patients hospitalized for major depressive disorder. Insomnia diminished in all patients after 2 weeks of drug administration. After 4 weeks, the sleep of patients whose depressive disorder has significantly improved was nearly normal, whereas patients who remained depressed showed continued sleep impairment. Reductions in loss of appetite, weight and sexual interest paralleled mood improvement. Tricyclic plasma levels significantly correlated with improved sleep. The findings suggest a close link between depressed mood and physical symptoms during recovery from major depressive disorder.

Adult↗
PubMed1984

3H-imipramine binding in human platelets: a study in normal twins.

3H-imipramine binding was determined in freshly prepared intact platelets from 17 monozygotic (MZ) and 15 dizygotic (DZ) twin pairs, all of them male, adult, drug-free, and healthy volunteers. Sixteen males served as controls for determination of intraindividual variation of binding parameters. Both MZ and DZ twin pairs exhibited high intraclass correlations of Bmax values, but DZ twins were nearly as similar as MZ pairs. Interindividual variation of binding parameters is not large enough to reveal a significant genetic control.

Adult↗
PubMed1984

Platelet imipramine binding in autistic subjects.

Previous reports of elevated platelet serotonin (5-HT) concentrations in autistic subjects suggest that platelet 5-HT uptake might be altered in autism. Parameters of 3H-imipramine (IMI) binding were measured in 11 drug-free autistic subjects and 10 normal volunteers. Similar means (+/- SD) for Bmax (autistics, 1350 +/- fmole/mg protein; normals, 1590 +/- 206 fmole/mg protein) and Kd (autistics, 0.98 +/- 0.10 nM; normals, 0.94 +/- 0.13 nM) were found in the two groups. The normal number (Bmax) and affinity (Kd) of the IMI binding site in autistic subjects suggest that the regulation of 5-HT uptake is not different in autism.

Adolescent↗
PubMed1985

Tritiated imipramine binding to platelets is decreased in patients with agoraphobia.

Controversy exists regarding the relationship between anxiety states and major depression. We studied the binding of tritiated imipramine to platelet membranes in order to determine if patients with agoraphobia and panic attacks differed from depressed subjects or healthy volunteers on this biological parameter. Mean (+/- SD) Bmax and Kd values were significantly lower in patients with agoraphobia and panic attacks (787 +/- 276 fmole/mg protein and 0.35 +/- 0.14 nM, respectively) than in healthy volunteers (1237 +/- 201 fmole/mg protein and 0.71 +/- 0.37 nM, respectively). In addition, patients with agoraphobia and panic attacks had binding parameters that were similar to those of patients with bipolar or familial pure depressive disorder, but significantly lower than those of patients with depressive spectrum or sporadic depressive disorder. These findings have implications for both the nosology and pathophysiology of anxiety disorders.

Adolescent↗
PubMed1985

Platelet 3H-imipramine binding in pregnancy and the puerperium.

Platelet 3H-imipramine binding was examined in a cross-sectional study of 70 Caucasian women in pregnancy and the early post-partum period, and in 23 nonpregnant women of childbearing age. Mood was also assessed in the pregnancy and post-partum sample. No significant differences in number of binding sites (Bmax) were found, but an increase in the equilibrium dissociation constant (Kd) was demonstrated at 5-7 days post-partum.

Adult↗