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PubMedDate not supplied

Influence of chronic imipramine administration on the CaM-KII activity in postsynaptic densities and synaptosomal plasma membrane fraction isolated from the rat frontal cortex and hippocampus.

CaM-KII exhibits broad distribution within neurons and discrete localization inside the cell, and it is highly abundant in the postsynaptic densities. The aim of the present study was to investigate the influence of chronic imipramine administration on the CaM-KII activity in postsynaptic densities and synaptosomal plasma membrane fraction isolated from the rat frontal cortex and hippocampus. In the present study, we showed that chronic imipramine administration did not affect the CaM-KII activity localized postsynaptically. Moreover, our results indicated that chronic imipramine treatment evoked a large (300%) increase in CaM-KII activity in synaptosomal plasma membranes fraction isolated from frontal cortex.

Animals↗
PubMed2001

Effects of nefazodone on body weight: a pooled analysis of selective serotonin reuptake inhibitor- and imipramine-controlled trials.

BACKGROUND: Evidence suggests that the newer antidepressant drugs may differ with respect to their effects on body weight, especially during long-term treatment. However, the published data about treatment-emergent weight change with the newer antidepressants are limited. Most reports of unexpected selective serotonin reuptake inhibitor (SSRI)-associated weight gain are anecdotal or from small controlled trials. To determine if differences exist among the newer antidepressants, the authors retrospectively analyzed data from clinical trials comparing nefazodone with SSRIs and with imipramine. METHOD: Weight change data supplied by Bristol-Myers Squibb from 6 completed clinical trials comparing the antidepressant nefazodone (N = 523) with 3 SSRIs, fluoxetine, sertraline, and paroxetine (N = 513), as well as 3 trials comparing nefazodone (N = 225) with the tricyclic antidepressant imipramine (N = 224) were analyzed. In all studies, nefazodone was found to be equal in efficacy to the comparator antidepressants. Studies that included both acute and long-term treatment phases were included in the analysis. Acute phases of the trials lasted either 6 or 8 weeks, and long-term phases varied in duration from 16 to 46 weeks. The analysis included summarizing the number and percentage of patients in each group with a > or = 7% change in body weight from baseline at any point in the long-term and acute phases, at endpoint, and at week 16 of the long-term phases. RESULTS: Using 7% or greater weight change as the measure of clinical significance, 4.3% of SSRI-treated patients had lost weight at any point in the acute phase versus 1.7% of those treated with nefazodone (p = .017). However, at any point during the long-term phase, significantly more SSRI-treated patients than nefazodone-treated patients showed a significant increase in body weight (17.9% vs. 8.3%; p = .003). At any point in the acute phase, significantly more imipramine-treated patients than nefazodone-treated patients had a 7% or greater increase in body weight (4.9% vs. 0.9%; p = .027), and for the long-term phase the comparison yielded 24.5% versus 9.5%. The difference during the long-term phase was statistically significant in women (p = .017), but not in men (p = .078) due to the small numbers of men in each group. CONCLUSION: SSRIs caused more weight loss during short-term treatment but more weight gain during long-term treatment. These results lend support to the observation that some antidepressants have a greater expected risk of weight gain than others during long-term therapy.

Antidepressive Agents, Second-Generation↗
PubMedDate not supplied

Rise in zinc affinity for the NMDA receptor evoked by chronic imipramine is species-specific.

Zinc and magnesium are potent inhibitors of the NMDA receptor complex. Previous reports demonstrated that both zinc and magnesium, like other NMDA receptor antagonists, exhibit antidepressant-like effects in rodent screening tests. Moreover, chronic treatment with antidepressants and electroconvulsive shock increase zinc concentration in the rat hippocampus. The present study examined the effect of tricyclic antidepressant, imipramine, on the potency of zinc and magnesium to inhibit [3H]MK-801 binding in the mouse and rat cerebral cortex and hippocampus. Chronic treatment with imipramine produced statistically significant increase in the potency of zinc to inhibit [3H]MK-801 binding in the mouse cerebral cortex but not in the hippocampus. However, this treatment neither influenced the zinc affinity in rat tissue nor magnesium affinity in tissue of both species. The present data indicate that, although imipramine-induced rise in zinc affinity to the NMDA receptor complex is in agreement with previously reported antidepressant-induced reduction of the NMDA receptor function, this effect is species-specific.

Animals↗
PubMed1975

Use of synthesis inhibitors in defining a role for biogenic amines during imipramine treatment in depressed patients.

Endogenously depressed patients who showed an antidepressant response to the tricyclic drug imipramine continued to show sustained well being after alpha-MPT was added whereas depression returned when small doses of PCPA were added for brief periods. In one patient the antidepressant response to imipramine occurred after pre- and continued treatment with alpha-MPT. Urinary excretion levels of MHPG in one of the patients studied longitudinally did not correspond to the direction of clinical affective state but did reflect anticipated changes during alpha-MPT treatment. Implications are that serotonergic mechanisms are likely involved in the anti-depressant effects of imipramine in man.

3-Methoxy-4-hydroxyphenylethanol↗
PubMed1992

[Imipramine withdrawal syndrome during a treatment for enuresis].

The authors report on an observation of imipramine withdrawal syndrome which appeared when tapering the treatment of a case of bed-wetting. Symptoms included vomiting, digestive intolerance and dehydration. Such a presentation can mislead diagnosis towards abdominal or neurosurgical pathology. All symptoms disappeared after a symptomatic treatment or in combination with the return of imipramine. It is therefore important to be aware of this complication before prescribing imipramine treatment for enuresis. The discontinuation of this drug must be very progressive.

Adolescent↗
PubMed1992

A 6-week, double-blind trial of paroxetine, imipramine, and placebo in depressed outpatients.

Paroxetine is a novel antidepressant that selectively inhibits neuronal reuptake of serotonin. Results are reported from a 6-week, double-blind trial of paroxetine, imipramine, and placebo in 120 outpatients with DSM-III major depression. Paroxetine was significantly superior to placebo on almost all measures. This included the main outcome variable, the Hamilton Rating Scale for Depression (HAM-D), and its factor scores, anxiety-somatization, cognitive disturbance, psychomotor retardation, and sleep disturbance. There were no significant differences between paroxetine and imipramine on the same scales. Imipramine-treated patients were significantly more likely than those taking placebo to report one or more adverse effects, which were predominantly anticholinergic in nature. There was no significant difference in the number of paroxetine and placebo patients who reported one or more adverse effects. The results of this and similar studies indicate that paroxetine is an effective treatment in major depression and has a favorable side effect profile.

Adult↗
PubMed1992

Paroxetine in the treatment of depression: a comparison with imipramine and placebo.

Paroxetine is a selective serotonin reuptake inhibitor with significant antidepressant properties. This was a 6-week placebo- and imipramine-controlled study of 120 outpatients with major depression. Paroxetine was statistically significantly superior to placebo on almost all outcome measures. This was apparent as early as 1 week. Paroxetine was also significantly superior to imipramine on the Hamilton Rating Scale for Depression total score. Paroxetine was generally better tolerated than imipramine. These results strongly support paroxetine's effectiveness in the treatment of major depression and suggest that paroxetine will be a valuable addition to the options in treating depressive illness.

Adolescent↗
PubMedDate not supplied

Effect of imipramine treatment on plasma dopamine beta-hydroxylase activity in chronic mild stress in rats.

Dopamine beta-hydroxylase (DBH) which catalyzes conversion of dopamine into noradrenaline, may be a good blood marker of unipolar depression. Therefore, we studied the effect of classic antidepressant drug imipramine (10 mg/kg ip) on activity of this enzyme in plasma of rats subjected to chronic mild stress (CMS), the model of anhedonia. CMS induced reductions in DBH activity by the second day and 5th week of stress duration. Imipramine treatment minimized these CMS-induced reductions. The data indicate that, similarly to human depression, CMS also affects DBH activity, and, moreover, the CMS-induced alterations are normalized by imipramine treatment.

Animals↗
PubMedDate not supplied

Role of emotionality on inter and intrastrain variations in imipramine response. a comparative study in Balb/c and Swiss mice.

Association between emotionality and effect of imipramine on immobility time in forced swimming test was investigated in Swiss and Balb/c mice. Mice of both the strains were segregated into normal emotional (mean +/- 1SD), low emotional (> mean + 1SD) and high emotional (< mean - 1SD) based on their performance with respect to each indices of emotionality in novel arena and elevated plus maze. Baseline immobility and effect of imipramine (20 mg/kg, po) on immobility time was evaluated in these emotionally different groups of mice using forced swimming test model. Baseline immobility time of low emotional mice was found to be significantly less (P<0.01) and that of high emotional mice was found to be significantly more (P<0.01) when compared to normal emotional mice of both the strains. Immobility time after imipramine administration was found to be significantly less (P<0.05) with low emotional mice and significantly more (P<0.01) with high emotional mice when compared to normal emotional mice of both the strains.

Animals↗
PubMedDate not supplied

[Value of adjuvant treatment with imipramine for lumbosacral pain syndrome].

The antidepressants have been reported to be effective in the treatment of many pain syndromes, for example headache and neuralgia. The pain of the study was to evaluate the effectiveness on small (75 mg per die) dose of imipramine administered additionally to the routine. Conservative treatment of patients with acute low back pain. The analysis of six different indices of improvement revealed, that the outcome of therapy in the group of 50 patients treated with imipramine was significantly better, than in comparable group treated routinely. The effect of imipramine have not been related to the occurrence of depression or to the other factors from anamnesis and physical examination influencing pain.

Adult↗
PubMed1991

Platelet [3H]imipramine and alpha 2-adrenoceptor binding in normal subjects during desipramine administration and withdrawal.

The effect of desipramine 150 mg daily on platelet [3H]imipramine and alpha 2-adrenoceptor binding sites was studied over a 6-week period and for 6 weeks after withdrawal. Modest (10%) increases in [3H]imipramine binding site densities during treatment were noted with a decrease between 1 and 4 weeks after withdrawal. No effect was found on alpha 2-adrenoceptors. Time of day appeared to have some effect on the results found. None of the [3H]imipramine binding site effects of desipramine, on treatment or following withdrawal, was comparable in magnitude to trait differences that were also found between subjects.

Adult↗
PubMedDate not supplied

Comparison of the cardiovascular effects of amineptine with those of amitriptyline and imipramine in anaesthetized rats.

In this study, two tricyclic antidepressant drugs and amineptine, administered to anaesthetized rats by intravenous bolus injection, were compared with regard to their in vivo cardiovascular effects. Amitriptyline and imipramine decreased mean arterial blood pressure and heart rate and caused conduction and rhythm changes in ECG. Amineptine, on the other hand, increased mean arterial blood pressure and caused a transient reduction of heart rate only at doses higher than those of amitriptyline and imipramine, while producing no noticeable ECG effects, even at doses 8 times higher than for the two tricyclic antidepressant drugs. The results of this study imply that amineptine, which structurally resembles tricyclic antidepressant drugs in having three rings and a side chain, has, nevertheless, a pattern of cardiovascular effects differing from that of amitriptyline and imipramine.

Amitriptyline↗
PubMed1991

Prediction of steady-state plasma levels of doxepin and imipramine from single dose levels in depressed outpatients.

We have investigated the predictive value of single dose levels for steady state levels of two commonly used antidepressants, doxepin (DOX) and imipramine (IMI) in a population of 40 outpatients with unipolar depression. After a wash-out period, patients were given 75 mg of either doxepin or imipramine and blood samples were drawn 16 h after the dose. Treatment was continued for 2 weeks on a fixed 100 mg/day dose and after that the dose was adjusted according to patients' response. Drugs and their demethylated metabolites were determined weekly using a GC technique. There was a large (more than 5-fold) inter-individual variation in both the single dose and steady-state levels of the two drugs. However, a significant correlation was found between the single-dose levels and initial steady-state levels for both. The respective linear regression equations were: DOX (parent drug & demethylated metabolite): y = 1.4x + 16.8; r = 0.75, p less than 0.001; IMI (parent drug & demethylated metabolite): y = 3.1x + 4.9; r = 0.85; p less than 0.001. These results confirm, in a population of depressed outpatients, previous findings of a significant correlation between single dose and steady state plasma levels of imipramine, and indicate for the first time that such a correlation also exists for another commonly used tricyclic antidepressant, doxepin. From this relationship, dose requirement can be estimated for individual patients to achieve a desired steady-state concentration of total tricyclics (parent drug & metabolite).

Adolescent↗
PubMedDate not supplied

[Cerebral aminopeptidase activity: effect of the administration of imipramine].

Imipramine is widely accepted as an effective antidepressant treatment. In this paper, changes in Lys- and Leu-aminopeptidase activities in several rat brain regions after imipramine treatment are described. Decreases of Lys-aminopeptidase activity in the olphactory bulbus, cerebellum, hypothalamus and pituitary gland were observed. In the same way, there were a decreases in Leu-aminopeptidase activity in the parietal and occipital cortices, cerebellum thalamus, hypothalamus and pituitary gland. It is suggested that these enzyme activities play a part in the imipramine action mechanism, possibly by regulating the activity of several neuroactive peptides.

Aminopeptidases↗
PubMed1990

Antidepressant binding sites in brain: autoradiographic comparison of [3H]paroxetine and [3H]imipramine localization and relationship to serotonin transporter.

Binding of two different antidepressant drugs, [3H]paroxetine and [3H]imipramine in 30 rat brain regions was visualized, compared and quantified by means of autoradiography and densitometry. Specific binding of [3H]paroxetine to coronal sections of diencephalon represented 85% of total binding and was saturable and of high affinity (KD, 0.36 +/- 0.07 nM) with a maximum number of binding sites of 276 +/- 41 fmol/mg protein. The autoradiograms showed a heterogenous distribution of [3H]paroxetine in brain with selective accumulation of label in brain regions known to contain serotonergic terminals, axons and cell bodies (amygdaloid and raphe nuclei, superior colliculus, substantia nigra and medial forebrain bundle). Binding was displaced selectively with other serotonin uptake inhibitors (clomipramine and fluoxetine) and almost abolished by lesioning the serotonergic neurons with p-chloroamphetamine. The desipramine-sensitive [3H]imipramine binding was more diffuse with relatively high density in cerebral cortex and hippocampus and was only decreased partially in animals treated with p-chloroamphetamine. The results indicate that [3H]paroxetine, but not [3H]imipramine, is a ligand of choice to selectively label serotonergic structures in brain.

Animals↗
PubMed1990

A placebo- and imipramine-controlled study of paroxetine.

The objective of this study was to compare the safety and efficacy of paroxetine with imipramine and placebo in depressed outpatients. Following a 4- to 14-day placebo washout, patients were randomized into treatment groups and received study compound for up to 42 days. At Day 42, paroxetine was significantly more effective than placebo (p less than .05) in several observer- and patient-rated scales: the Retardation and Anxiety/Somatization factors of the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), the Raskin Depression Scale, the Covi Anxiety Scale, the Clinical Global Impressions (CGI) Improvement Scale, the Symptom Checklist-56 (SCL-56) Total, and the Patient's Global Evaluation (PGE). There were no significant differences between paroxetine and imipramine. Significantly more imipramine (75%) than paroxetine (35%) or placebo (23%) patients reported anticholinergic side effects, including blurred vision (5%, 0%, and 0%, respectively), constipation (35%, 8%, and 15%, respectively), and dry mouth (63%, 25%, and 15%, respectively). The data from this study indicated that paroxetine is a safe, well-tolerated, effective treatment for major depressive disorder.

Adult↗
PubMed1990

The effect of long-term imipramine treatment on carbon dioxide-induced anxiety in panic disorder patients.

The authors examined whether long-term treatment with imipramine would decrease CO2-induced anxiety in 10 patients with panic disorder. The patients underwent CO2 testing after single-blind placebo testing and again after imipramine treatment. Scores on self-rated visual analog mood scales and panic attack symptom scales showed that the anxiogenic effects of CO2 were significantly reduced during long-term imipramine treatment. These results suggest that the mechanisms underlying CO2-induced anxiety may be similar to those involved in the pathophysiology of panic disorder.

Adult↗
PubMed1990

[Management of primary nocturnal enuresis in school children with slow learning ability: usefulness of imipramine].

A comparative, longitudinal, blind prospective study was carried out in 20 students between the ages of 6 and sixteen with primary nocturnal bedwetting and slow learning abilities from the Fray Antonio Alcalde school, in order to evaluate the use of motivating reinforcement techniques, exercises in order to improve bladder function and treatment with imipramine. All of the patients were given motivation reinforcement and bladder exercises. They were later divided into two groups of 10 children; group A was given a placebo while group B was given imipramine. In group A a significant decrease was seen in the average number of days the children woke wet after the sixth month of treatment (13.2 +/- 9.7 days to 3.7 +/- 7.15 days) with P less than 0.05; and in group B since the fourth month (16.6 +/- 7.8 days to 8.1 +/- 8.3 days) with a P less than 0.05. At the end of the study, seven patients from group A and five patients from group B decreased in over 80% the number of days which they woke up wet. The motivating reinforcement and the exercises used to improve bladder functional capacity are useful in the management of primary nocturnal enuresis. Imipramine, when combined with these other routines can shorten the time towards a favorable response.

Adolescent↗