Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “IMIPRAMINE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 631 records · Page 35Linked to original sources
PubMed1996

Imipramine treatment of alcoholics with primary depression: A placebo-controlled clinical trial.

BACKGROUND: Depressive disorders are commonly comorbid with alcoholism, particularly in treatment-seeking samples. If antidepressant treatment were safe and improved the treatment outcome in the subset of actively drinking alcoholics with depression, this would be of clinical importance. METHODS: We conducted a randomized, 12-week placebo-controlled trial of imipramine hydrochloride combined with weekly relapse prevention psychotherapy. The subjects were 69 actively drinking alcoholic outpatients with current depressive disorders. The first onset of depression was either antecedent to the abuse of alcohol or occurred during prolonged periods of sobriety. Depression and drinking outcomes at 12 weeks, as well as their relationship, were measured. RESULTS: Imipramine treatment was safe and associated with improvement in depression in both adequately treated and intention-to-treat samples. While there was no overall effect on drinking outcome, patients whose mood improved showed decreased alcohol consumption that was more marked in those treated with imipramine. CONCLUSIONS: Imipramine treatment is effective for primary depression among actively drinking alcoholic outpatients, and may improve alcoholic outcome for those whose depression responds to treatment.

Adult↗
PubMed1992

Clinical experiments in maintenance and discontinuation of imipramine therapy in panic disorder with agoraphobia.

Several issues remain to be ascertained beyond the acute response to imipramine hydrochloride in patients with panic disorder. Study 1 consisted of a prospective, systematic characterization of half-dose 12-month maintenance in patients with panic disorder with agoraphobia who had shown marked and stable response to 6 months of acute-phase treatment with imipramine. Study 2 assessed the 6-month cumulative relapse rate following discontinuation of acute-phase imipramine treatment in a comparable sample of patients. The same assessment battery was used in both studies, and the integrity of experimental drug conditions was verified by plasma drug level determinations. In contrast to the high relapse rate following discontinuation of acute-phase treatment, none of the patients showed relapse or had sustained worsening in panic or phobia measures during the half-dose maintenance period. The results underscore the importance of pharmacological prophylaxis and provide empirical guidelines for a successful low-dose maintenance regimen for patients with panic disorder and agoraphobia who respond markedly to imipramine.

Adult↗
PubMed1986

Biochemical effects of antidepressant treatment--studies of monoamine metabolites in cerebrospinal fluid and platelet [3H]imipramine binding.

Two putative markers of serotonergic function, the concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and the binding parameters of [3H]imipramine to blood platelets, are discussed. Pretreatment concentrations of 5-HIAA in the cerebrospinal fluid (CSF) are lower in depressed patients than in normal controls, and a low concentration of the metabolite is associated with an increased risk of suicide. Many studies have attempted to use pretreatment concentrations of 5-HIAA, of the noradrenaline metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) and of the dopamine metabolite homovanillic acid (HVA) as predictors of therapeutic effect. On the whole, HVA appears to predict the effects of diverse treatments rather better than 5-HIAA. Treatment with antidepressant drugs changes the amine metabolite concentrations in the CSF in a relatively predictable way. Thus, administration of selective inhibitors of serotonin uptake has a more profound effect on CSF 5-HIAA, while noradrenaline uptake inhibitors preferentially reduce CSF MHPG concentrations. The Bmax of [3H]imipramine binding to blood platelets has been found to be lower in untreated depressed patients than in healthy controls in several studies. In a study from our group, three weeks' treatment with the serotonin uptake blockers zimeldine and alaproclate increased Bmax, while neither nortriptyline nor electroconvulsive treatment caused any change in Bmax after this time period. One year after initiation of treatment, patients who had clinically recovered and were no longer taking drugs still had a low Bmax of [3H]imipramine platelet binding. Prophylactic lithium caused a significant, but transient decrease in the Bmax of platelet [3H]imipramine binding in euthymic bipolar patients.

Antidepressive Agents↗
PubMed1979

Binding of imipramine to plasma proteins: effect of hyperlipoproteinemia.

The binding of imipramine to plasma proteins was studied by equilibrium gel filtration. Imipramine was highly bound to lipoproteins as well as to other plasma proteins. The binding to the lipoproteins was higher in hyperlipoproteinemic patients than in normal subjects and correlated well with both plasma cholesterol and triglyceride levels. The overall percent binding of imipramine was also higher in hyperlipoproteinemic patients than in normal subjects. It is concluded that the varying degree of binding of imipramine to plasma proteins as a result of varying lipoprotein concentrations, as well as the special nature of the binding to lipoproteins, may be of kinetic and possibly clinical significance in hyperlipoproteinemic individuals.

Blood Proteins↗
PubMed1988

Genotoxicity evaluation of the tricyclic antidepressants amitriptyline and imipramine using human lymphocyte cultures.

Two tricyclic antidepressants, amitriptyline and imipramine, were evaluated for their in vitro cytogenetic effects in human lymphocyte cultures. Peripheral blood cultures from three normal healthy donors were set up for 72 hr for each of the drugs. The drugs were added at the start (72-hr exposure), 24 hr (48-hr exposure), and 48 hr (24-hr exposure) after initiation of the cultures. The concentrations evaluated at each exposure time were 50, 250, 1,000, and 10,000 ng/ml for amitriptyline and 25, 500, and 5,000 ng/ml for imipramine. The first two concentrations correspond to the plasma levels of the respective drugs after therapeutic doses. All treatments for a donor were given at the same time. Untreated cultures served as controls for the baseline frequency of the parameters assayed. The parameters assayed were chromosome aberrations, mitotic index, and sister chromatid exchanges (SCEs). Amitriptyline was found to be nongenotoxic at plasma levels by all the parameters assayed. However, frequencies of chromosome aberrations and SCEs were significantly increased at concentrations 4 and 40 times the plasma level (1,000 and 10,000 ng/ml) although the actual increases was small. The mitotic index was not affected at any concentration. Through imipramine showed a significant increase in chromosome damage at the upper plasma level and at concentrations higher than that, SCE frequency was significantly increased only at concentration higher than the plasma level (5,000 ng/ml), the actual increase being small for both these parameters. The mitotic index was not affected at any concentration. These results suggest that amitriptyline may be a slightly safer drug than imipramine from a genetic point of view.

Amitriptyline↗
PubMed1987

Imipramine treatment alters the pharmacokinetics and pharmacodynamics of diazepam.

This report describes observations of the relationship between the pharmacokinetics and pharmacodynamics of diazepam (7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one ; 5 mg/kg) during the concomitant administration of diazepam and imipramine hydrochloride (5-[3-(dimethylamino)propyl]-10,11-dihydro-5H-dibenz[b,f]azepine monohydrochloride; 20 and 50 mg/kg) to rats. We measured plasma, brain, and liver concentrations of diazepam and its metabolites in rats by high-performance liquid chromatography. The concomitant use of imipramine hydrochloride increased diazepam and desmethyldiazepam concentrations, but decreased temazepam and oxazepam concentrations in rat plasma. Diazepam plasma protein binding was unaltered. The liver concentrations of diazepam and its metabolites showed similar changes in their plasma concentrations. The concomitant use of imipramine hydrochloride increased the concentrations of diazepam and its metabolites in the brain. We also studied the effect of benzodiazepines on convulsions induced by pentylenetetrazole (6,7,8,9-tetrahydro-5H-tetrazolo[1,5-a] azepine; 135 mg/kg) in rats. The concomitant use of imipramine hydrochloride led to an increased antipentylenetetrazole effect of diazepam. This result is in accordance with the findings on brain concentrations of diazepam and its metabolites.

Animals↗
PubMed1986

Adinazolam, a new triazolobenzodiazepine, and imipramine in the treatment of major depressive disorder.

This study evaluated the clinical efficacy and safety of a new triazolobenzodiazepine, adinazolam, and imipramine in 40 patients with carefully diagnosed major depressive disorder. Overall, adinazolam was found to be as effective as imipramine. In addition, when patients with more severe, melancholic, subtype of depression were examined, adinazolam was also as effective as imipramine. With the exception of sedation, adinazolam patients demonstrated fewer overall adverse events than imipramine subjects. These results suggest that adinazolam may represent an interesting antidepressant compound.

Adolescent↗
PubMed1988

Short-term lithium administration to healthy volunteers produces long-lasting pronounced changes in platelet serotonin uptake but not imipramine binding.

Platelet [3H]-5HT uptake, [3H]-imipramine binding and endogenous 5HT levels were measured in healthy volunteers during short-term (20 days) administration of lithium, and following its withdrawal. The Vmax of [3H]-5HT uptake was significantly decreased during lithium treatment. Following lithium withdrawal, platelet [3H]-5HT uptake (Vmax) remained decreased and was followed by a pronounced rebound effect in some of the subjects for up to 3 months. The affinity constant (Km) of [3H]-5HT uptake was not modified. Binding of tritiated imipramine during the same period and platelet 5HT levels measured till 14 days after withdrawal was not affected by lithium treatment. As lithium is devoid of in vitro effects on both 5HT uptake and imipramine binding, it is concluded that the effects of lithium on the 5HT transporter do not reflect a direct effect on the transporter complex. Our results indicate that lithium-induced changes at the level of 5HT uptake in platelets are not correlated with concomitant variations in platelet 5HT content and can be dissociated from modifications at the level of imipramine binding sites within the macromolecular complex of the 5HT transporter. Moreover, platelet 5HT uptake is apparently modulated by lithium, with a similar pattern in healthy volunteers and in manic-depressive patients.

Adult↗
PubMed1976

Irreversible protein binding of 14C-imipramine in rats in vivo.

Forty-eight hours after a single dose of 14C-imipramine to rats, 14C-radioactivity could be measured in the following organs: liver greater than kidney greater than serum greater than fat greater than spleen greater than duodenum greater than lung greater than muscle and brain. Liver microsomes contained the main part of radioactivity derived from 14C-imipramine. After exhaustive extraction, only the proteins of liver, kidney, spleen, lung and serum contained measurable amounts of radioactive labeling. The greatest amount of 14C-imipramine irreversibly bound to proteins was detected in liver microsomes. The question, as to whether the irreversible protein binding of imipramine, if it occurs during therapy, results in toxic side-effects, is discussed.

Animals↗
PubMed1975

[Plasma levels of imipramine and desmethylimipramine and antidepressant effect during controlled therapy(author's transl)].

24 depressed impatients received a standardized treatment by imipramine, 6 among them receiving also levomepromazine. Plasma concentration of imipramine and DMI were controlled weekly during the study, and standardized assessment of clinical state were made by a psychiatrist who was unware of biochemical findings. Interaction between the antidepressant and neuroleptic metabolism is shown by a significant increase of DMI levels, though the clinical effect of the drug association could not be asserted. The therapeutic effect seems mainly dependant of etiology of depression. Endogeneous depressions improve more than other types. Among endogenous depressions a significant correlation was found between the degree of clinical improvement after three weeks and DMI level, sum of imipramine + DMI level, but not with concentration of imipramine alone.

Adjustment Disorders↗
PubMed1977

The demethylation of imipramine and clomipramine as apparent from their plasma kinetics.

The demetylation of imipramine and clomipramine was studied after administration by different routes of single doses of clomipramine hydrochloride and multiple doses of clomipramine as well as imipramine hydrochloride. Five healthy volunteers received 1 mg of clomipramine hydrochloride/kg body weight as single oral and intramuscular doses on different occasions for the purpose of studying the plasma levels of clomipramine and the desmethylclomipramine formed. Desmethylclomipramine was found in the plasma in four of the subjects after oral intake but only in one subject after intramuscular injection. The peak levels of clomipramine were considerably higher after intramuscular than after oral administration. The half-lives of clomipramine after oral administration ranged from 11.6-35.8 h (M = 20.8 +/- 4.0) and after intramuscular administration from 20.1--39.6 h (M = 24.7 +/- 3.7). Twenty subjects received either imipramine or clomipramine both orally and intramuscularly during a period of 3 weeks in a crossover design. The plasma levels of imipramine and clomipramine and their demethylated metabolites desipramine and desmethylclomipramine were determined during the treatment. The ratio between the plasma level of the parent drug and its demethylated metabolite was on average twice as high during intramuscular as during oral treatment.

Administration, Oral↗
PubMed1980

Comparison of single-dose pharmacokinetics of imipramine and maprotiline in the elderly.

Pharmacokinetic profiles of imipramine and a newer tetracyclic antidepressant, maprotiline, were studied in elderly (75-83 years of age) subjects who were given a single oral dose of 125 and 175 mg, respectively, of these drugs. The apparent elimination half-life of imipramine was 20.8-34.9h (means 26.4h), its biovailability (F) was 40-64% (means 57%), and the apparent plasma clearance was from 0.27-0.57h/kg (mean 0.41h/kg). Maprotiline had a longer half-life (mean 31.5h range 20.6-51.8h, but its bioavailability (mean 50%) and plasma clearance (mean 0.49h/kg) values were in the range similar to those seen after imipramine. It appears that the elimination half-life of imipramine is longer and its plasma clearance is markedly reduced in elderly subjects when compared to values reported in young adults. Subjective clinical side effects were minimal with the two drugs. However, alterations in heart rate, blood pressure, or electrocardiogram occurred in all subjects. This suggests that caution should be exercised before initiating and during the treatment of elderly patients with these antidepressant drugs.

Aged↗
PubMed1985

Fear-enhanced acoustic startle is not attenuated by acute or chronic imipramine treatment in rats.

The effect of acute or chronic administration of imipramine on fear-enhanced startle (potentiated startle) in rats was investigated. Thirty male albino rats were initially given preliminary startle testing, assigned to one of three matched groups, and trained for potentiated startle by presenting ten light-shock pairings on each of 2 days. Subsequent startle testing following a single injection of 0, 5 or 10 mg/kg imipramine revealed that the degree of startle potentiation (increased responding in the presence of the light previously paired with shock) was similar across treatment conditions. A significant and comparable potentiation of startle was observed in animals treated chronically with saline or imipramine (10 mg/kg/day) for 21 days between training and testing. Potentiated startle was also observed in these animals on the next (22 nd) day after injection of an additional dose of the drug (10 mg/kg) 5 min prior to testing. Plasma levels of imipramine and its metabolite, desipramine, were relatively high after each of these treatments. Since previous studies have shown that potentiated startle is decreased by diazepam, the present findings suggest that the potentiated startle paradigm is a valid model for studying simple fear or anxiety rather than panic disorder.

Acoustic Stimulation↗
PubMed1981

Dose-dependent kinetics of imipramine in elderly patients.

In a group of elderly depressed patients treated with imipramine (50-200 mg/day), six patients had the dose changed after 1-3 weeks of treatment. In all cases an increased dose resulted in a considerably disproportional rise in the plasma level of the active metabolite desipramine. In a group of elderly depressed patients treated with nortriptyline (40-100 mg/day) the dose/plasma level ratio could be examined in 6 patients, and there was no tendency towards a disproportional rise in plasma level, when the dose was raised. Dose changes, thus, may result in unpredictable changes in plasma levels during imipramine treatment and therapy control by plasma level monitoring may be difficult in these patients. Additional treatment with perphenazine (8-16 mg/day) to patients on imipramine (N = 3) or nortriptyline (N = 2) caused a marked rise in drug levels for imipramine in particular affecting the desipramine levels.

Aged↗
PubMed1986

Reversal of the reserpine-induced ptosis by L-threo-3,4-dihydroxy-phenylserine (L-threo-DOPS), a (-)-norepinephrine precursor, and its potentiation by imipramine or nialamide.

The effect of L-threo-DOPS on the reserpine-induced ptosis in mice and its modification by imipramine, a norepinephrine (NE) uptake inhibitor, or nialamide, a monoamineoxidase inhibitor, were studied. Intraperitoneal (i.p.) injection of L-threo-DOPS (800 mg/kg) significantly reduced the severity of the ptosis. This reversal of the ptosis by L-threo-DOPS was markedly potentiated by i.p. injection of either imipramine (2.5 mg/kg) or nialamide (30 mg/kg). Response to L-threo-DOPS was also significantly potentiated by intracerebroventricular (i.c.v.) injection of imipramine (10 micrograms). On the other hand, this treatment with imipramine (10 micrograms, i.c.v.) also significantly potentiated the reversal of the ptosis by NE (20 micrograms, i.c.v.), but the reversal by the subcutaneous (s.c.) injection of NE (1 and 3 mg/kg) was not affected. Reserpine (5 mg/kg, i.p.) markedly decreased the brain content of NE in mice, whereas L-threo-DOPS (400 mg/kg, i.p.) slightly restored it. Moreover, by the pretreatment with nialamide (30 mg/kg, i.p.), L-threo-DOPS produced a significant increase in the brain content of NE in reserpine-treated mice. These results suggested that L-threo-DOPS was capable of reversing the reserpine-induced ptosis due to the formation, at least in part of (-)-NE at the synaptic sites of central noradrenergic neurons.

Animals↗
PubMed1975

The influence of imipramine on dopamine-induced ganglionic inhibition and neurogenic vasodilatation in the dog.

Imipramine potentiates the dopamine-induced inhibition in the paravertebral lumbar ganglia of the dog. Potentiation by imipramine of the dopamine-induced neurogenic vasodilatation in the isolated perfused gracilis muscle, is seen in cross-circulation preparations only, where imipramine is injected into the perfusion circuit of an isolated perfused gracilis muscle, it antagonizes the dopamine-induced neurogenic vasodilatation. When imipramine is injected intravenously into a dog with an autoperfused gracilis muscle, the peripheral antagonism masks the potentiating effect at the ganglionic level, and the dopamine-induced neurogenic vasodilatation is abolished.

Action Potentials↗
PubMed1977

The electroencephalographic and psychological effects of imipramine in depressed inpatients.

Ten patients with psychotic depression were assessed on a battery of clinical, EEG, psychological, and biochemical measures during treatment with imipramine (150 mg/day). Significant changes occurred in the scores on self-rated and observer-rated depression scales and on an observer-rated side effect scale. Significant changes also occurred in the EEG evoked response, but the effects on spontaneous activity were minimal. The psychological measures revealed an improvement in performance as treatment progressed. The clinical significance of the changes observed was assessed with reference to their correlations with the clinical rating scores and with the plasma concentrations of imipramine and desmethylimipramine, and the changes observed following the administration of imipramine to non-depressed normal subjects. Changes in evoked EEG activity seemed on balance to be direct central effects of imipramine, whereas changes in psychological performance appeared to be secondary to clinical change.

Adult↗
PubMed1979

DL-phenylalanine versus imipramine: a double-blind controlled study.

In a double-blind study, DL-phenylalanine (150--200 mg/24 h) or imipramine (150--200 mg/24 h) was administered to 40 depressed patients (20 patients in each group) for 30 days. Diagnoses were established according to the International Classification of Disease (ICD). The AMP system, the Hamilton Depression Scale and the Bf-S self rating questionnaire (von Zerssen et al., 1974) were used to document psychopathological, neurologic, and somatic changes. Twenty-seven patients (14 on imipramine, 13 on phenylalanine) completed the 30-day trial. No statistical difference could be found between these two drug treatment groups (Student's t-test) using the Hamilton Depression Scale and the Bf-S self rating questionnaire. Ratings for anxiety were significantly lower in the imipramine group on days 10 and 20, but not on day 30; in addition, sleep disturbances were more influenced by imipramine on days 1, 5, and 10, but not on days 20 and 30. Separate analysis of psychopathological syndromes as somatic depressive syndrome and retarded depressive syndrome did not show a group difference (0.05 level of significance using a two-way analysis of variance). It is concluded that DL-phenylalanine might have substantial antidepresant properties. However, certain methodological considerations still warrant a careful interpretation.

Adult↗