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At least 847 records · Page 47Linked to original sources
PubMed1985

Effect of imipramine and adrenocorticotropin administration on the rat brain norepinephrine-coupled cyclic nucleotide generating system: alterations in alpha and beta adrenergic components.

Continuous treatment (1-3 weeks) with imipramine or adrenocorticotropin (ACTH) decreases the responsiveness of the norepinephrine-coupled cyclic nucleotide generating system in rat brain cerebral cortex. Experiments were undertaken to determine which component of the second messenger system is influenced by the hormone and antidepressant. Neither treatment modified the amount or function of extractable stimulatory guanine nucleotide binding protein or the activities of adenylate cyclase or phosphodiesterase. While both imipramine and ACTH treatment decreased the cyclic AMP response to norepinephrine, only imipramine administration influenced the response to isoproterenol. ACTH treatment was found to reduce the alpha adrenergic potentiation of isoproterenol- and 2-chloroadenosine-stimulated cyclic AMP production, as well as reduce the sensitivity of the norepinephrine response to prazosin. These findings indicate that imipramine and ACTH treatments decrease the responsiveness of the rat brain norepinephrine-stimulated cyclic AMP generating system through actions on the alpha and beta adrenergic receptor components. The results suggest that noradrenergic receptor activity may be under the control of adrenal and/or pituitary hormones.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1978

A double-blind multicentre trial comparing mianserin with imipramine.

1. Fifty-four depressive in-patients aged 18-45 yr, were treated at random, in double-blind conditions, with mianserin 60 mg daily or imipramine 150 mg daily in three divided doses for 4 weeks. Nitrazepam and diazepam were also allowed if necessary. 2. There was no significant difference in antidepressant efficacy between the two groups, as assessed by the rating scales of Hamilton, Beck and Overall, the Brief Psychiatric Rating Scale, and a global clinical rating. 3. The overall frequency of side-effects was significantly lower with mianserin than with imipramine. Autonomic symptoms increased in severity during treatment with imipramine, but not with mianserin. 4. the patients treated with imipramine had a fall in blood pressure which was not observed during mianserin treatment.

Adjustment Disorders↗
PubMed1986

Agoraphobia: relative and combined effectiveness of therapist-assisted in vivo exposure and imipramine.

Sixty-two chronically agoraphobic patients completed a controlled study to assess the effects of 1) imipramine up to 200 mg/day (mean = 130 mg/day), 2) 12 weekly therapist-assisted in vivo exposure sessions (flooding), and 3) imipramine plus flooding. The control group received systematic therapeutic instructions for self-directed in vivo exposure (programmed practice). Clinical measures of global severity, phobia, panic, anxiety, depression, and behavioral performance tests were administered before treatment and at Weeks 4, 8, and 12 of treatment. Results revealed significant improvement in all groups on all measures over the course of treatment; almost a third of the control patients showed marked improvement. Imipramine had significant effects on improvement of phobias and markedly increased clinical response rates in patients receiving 150-200 mg/day. Less chronicity and severity of condition also predicted better clinical outcome. Flooding had limited effects above and beyond programmed practice, and no imipramine-flooding interactions effects were found.

Adult↗
PubMed1986

Repeated imipramine treatment increases the responsivity of the rat hippocampus to dopamine. An in vitro study.

The sensitivity of hippocampal neurons to dopamine was studied in hippocampal slices obtained from rats treated acutely (10 mg/kg) or repeatedly (10 mg/kg, 14 days, twice a day) with imipramine. In non-treated rats dopamine induced a slight excitation or depression of the firing rate of CA 1 pyramidal neurons in slice preparations. Hippocampal slices prepared from the imipramine-treated rats displayed greater changes in the firing rate after dopamine application. Repeated imipramine administration also increased the number of slices sensitive to dopamine. it is concluded that repeated imipramine administration induces supersensitivity of hippocampal dopamine receptors.

Action Potentials↗
PubMed1987

Imipramine and tinnitus.

Although tinnitus is listed among the rare neurologic side effects of tricyclic antidepressants, little is known about its prevalence, mechanism of development, course, and management. A chart review of 475 patients treated with tricyclic antidepressants indicated that tinnitus occurred in about 1% of the patients. The case vignettes of 5 patients who developed tinnitus in the course of imipramine therapy are presented. Each developed tinnitus in the second or third week of treatment with imipramine at daily dosages of 150-250 mg and at combined plasma imipramine-desipramine levels between 200-450 ng/ml. In each patient, tinnitus subsided spontaneously within 2-4 weeks of onset without any specific treatment, even though the daily dosage of imipramine and the plasma tricyclic levels were constant or increased. Possible mechanisms of development of tinnitus and implications for tricyclic antidepressant therapy are discussed.

Adult↗
PubMed1985

Mianserin and imipramine in the treatment of elderly depressed patients.

Fifty elderly depressed patients were randomly assigned to double-blind treatment, using a flexible dose schedule, with either mianserin 20-60 mg or imipramine 75-150 mg. Medication was continued for four weeks. Eleven patients withdrew from the study. At the end of treatment there were no significant differences between mianserin and imipramine in antidepressant efficacy. A significantly greater number of side-effects occurred in the imipramine group (dry mouth, days 7 and 14; faintness, dizziness, weakness, day 21). When treating elderly depressed patients mianserin may be preferred to imipramine because of a lower incidence of induced side-effects.

Aged↗
PubMed1985

A review of multicenter controlled studies of fluoxetine vs. imipramine and placebo in outpatients with major depressive disorder.

The efficacy of fluoxetine was evaluated in depressed patients in double-blind imipramine- and placebo-controlled clinical trials. Fluoxetine produced greater improvement than placebo on all major efficacy parameters and was comparable to imipramine with respect to the primary indicators of depression. Fluoxetine had significantly less associated anticholinergic effects, dizziness, drowsiness, somatosensory disturbance, and excessive sweating than imipramine. Although nausea occurred more frequently in fluoxetine patients, it was generally mild and well tolerated. A significantly smaller percentage of fluoxetine than imipramine patients terminated therapy because of adverse experiences.

Adolescent↗
PubMed1979

Effects of imipramine on cellular electrophysiological properties of cardiac Purkinje fibers.

The electrophysiological effects of imipramine (Tofranil) on cardiac Purkinje fibers were studied in vitro. Imipramine has a direct membrane action. It reduces excitatory inward current in Purkinje fibers, at least as measured by Vmax and conduction velocity. The mechanism of action of imipramine is probably by both reduction in gNa and marked slowing of the time constants of recovery of the rapid inward sodium current. Imipramine also reduces the action protential duration, decreasing the absolute refractory period. This effect is not seen with antiarrhythmic agents of the local anesthetic class, but it is similar to lidocaine. This effect may be a result of the decrease in steady-state gNa, but effects of the drug on other ionic conductances could play a role.

Action Potentials↗
PubMed1979

Epileptic phenomena induced in the cat by the antidepressants maprotiline, imipramine, clomipramine, and amitriptyline.

The epileptogenic properties of four tricyclic antidepressant drugs: maprotiline, imipramine, clomipramine, amitriptyline, were investigated in locally anesthetized cats immobilized with gallamine and supplied with neocortical, hippocampal, and reticular recording electrodes. The drugs were infused intravenously at a constant rate (0.5 or, in some cases, 0.25 mg/kg per min) up to a final dose of 45 mg/kg. Already in small doses (1 to 5 mg/kg) all four antidepressants produced local signs of epileptiform pathology. Generalized sustained discharges occurred, on the average, at between 20 and 25 mg/kg with all four drugs. Imipramine and amitriptyline, after the first or first few generalized discharges, led to a pattern of repeated short generalized seizures alternating with silent periods. Maprotiline invariably produced this later alternating pattern only after a 10- to 30-min period of a seminormal high amplitude pattern. Clomipramine assumed a position between maprotiline on the one hand and imipramine and amitriptyline on the other. Starting at doses of 2-4 mg/kg, imipramine, clomipramine and amitriptyline, all three being norepinephrine and serotonin uptake inhibitors, induced a high amplitude "sleep" pattern. Maprotiline, a norepinephrine uptake inhibitor, which is thought devoid of serotonin-uptake inhibiting properties, led to high amplitude slow waves only with doses of at least 12.5 to 15 mg/kg.

Amitriptyline↗
PubMed1969

Nocturnal enuresis: comparison of the effect of imipramine and dietary restriction on bladder capacity.

Fifty children with nocturnal enuresis have been studied with a view to determining maximum bladder capacities and frequency of micturition, and the changes induced by dietary treatment and imipramine. Of 50 children treated with imipramine, 31 were symptomatically cured. Fifteen of the 48 children treated by dietary measures were also symptomatically cured, but as nine had already been cured by imipramine the correct cure rate for dietary treatment, for reasons indicated in the text, may have been no more than seven of the 48 cases. Treatment on the above lines, in those who responded, led to an increase in bladder capacity and a fall in diurnal frequency of micturition.Because the bladder can enlarge under the above conditions it is concluded that the bladder in the average enuretic is functionally but not structurally small, and that when dietary manipulation helps, it does so by eliminating factors from the diet to which the bladder is sensitive. Imipramine, by contrast, is effective because it blocks peripherally this effect.

Adolescent↗
PubMedDate not supplied

[Effect of imipramine on the vasomotor tone, blood supply and activity of the heart].

In tests conducted on anesthetized cats it was shown that imipramine used in doses of 1 and 3 mg/kg causes hypertension, increases the vascular tone in the kidneys and limbs. In doses of 5 and 10 mg/kg the drug provokes a short-lived (1--3 minutes) hypertension with a subsequent prolonged drop of the arterial pressure. The tonicity of the kidney and limb arteries changes in the same way as the arterial pressure, but the vascular tone in the heart only falls. In these doses imipramine blocks the adrenergic transmission of the excitation from the sympathetic nerve to the effector, e. g. produces a sympatholytic effect. Imipramine in a dose of 1 mg/kg intensifies the coronary circulation and then the oxygen absorption by the heart increases to a still greater degree. This is attended by the development of tachycardia, a greater cardiac output and an intensified contractility of the myocardium. In doses of 5 and 10 mg/kg imipramine protractedly reduces the cardiac ejection, coronary blood flow and significantly lowers the contractile function of the heart muscle.

Animals↗
PubMed1984

Nomifensine vs. imipramine in depressed inpatients.

In a double-blind random assignment study, nomifensine was compared to imipramine in a population of depressed male inpatients (N = 36; ages 22-56 years). Nomifensine and imipramine in doses of 100-150 mg/day were found to be comparable over the 4-week treatment period on the Hamilton Depression Rating Scale and Clinical Global Impressions. The Self-Rating Symptom Scale showed differences favoring nomifensine for the Depression factor at Days 3, 7, and 10. In extensive laboratory analyses, no clinically important changes were seen within or between groups. Although differences were not significant, more discomforting side effects--specifically, anticholinergic, nervousness/restlessness, and sedation--were seen in the imipramine than the nomifensine group. These results indicate that nomifensine compares favorably with imipramine in the treatment of depressed inpatients.

Adult↗
PubMed1983

The use of imipramine in depressed patients with congestive heart failure.

Previous studies of left ventricular performance (LVP) in depressed patients receiving tricyclic antidepressants have been performed on patients without severe heart disease. This study reports the effect of imipramine hydrochloride on LVP, assessed by radionuclide angiography, in a group of depressed patients with notable preexisting left ventricular dysfunction. Ejection fraction was measured at rest by first-pass radionuclide angiography before and after treatment with imipramine. Ejection fraction was unchanged during treatment, but seven of 15 patients experienced orthostatic hypotension of such severity that administration of the drug had to be discontinued. Plasma concentrations of the drug were essentially twice those usually seen. It is important to appreciate that although imipramine does not further impair resting LVP, this does not mean it is without risk. The physician must watch carefully for orthostatic hypotension when using imipramine in depressed patients with impaired LVP.

Aged↗
PubMed1982

Depression in children: relationship between plasma imipramine levels and response.

The effects of imipramine treatment and plasma drug levels were studied in 20 prepubertal children (16 males, 4 females; age range 7-12 years) hospitalized for major depressive disorder (DSM-III criteria). No change in symptomatology was seen after 2 weeks of individual/group/family psychotherapy, but 12 children experienced a remission within 6 weeks of beginning imipramine. Response to the drug was concentration-dependent; of the children who achieved total tricyclic (imipramine plus desipramine) plasma levels of 125-225 ng/ml, 92% responded, compared with 25% of those outside this range. Antidepressant response was correlated both with total tricyclic plasma levels and with plasma desipramine levels (r = 0.72 and 0.56, respectively), but not with plasma levels of imipramine alone.

Age Factors↗
PubMed1981

Specific responses to imipramine and doxepin in psychoneurotic depressed patients with sleep disturbance.

The pretreatment characteristics and symptomatology that were predictive of rapid response to pharmacotherapy (imipramine or doxepin) were determined in 79 psychoneurotic depressed patients with sleep disturbance. Rapid response to treatment was measured as at least a 50% reduction in total score for the Hamilton Rating Scale for Depression after two weeks of treatment. Pretreatment severity of illness and pretreatment scoring of the somatization factor on the Hamilton Rating Scale for Depression and of the self-rating of illness on the Lipman-Rickels Scale were found to be modest predictors of response to either drug. Estimation of imipramine and doxepin response groups was more successful. A higher socioeconomic status and shorter duration of illness were indicative of a favorable response to imipramine, whereas a higher response rate to doxepin was found in male patients. The four group discriminations showed a similarity in pretreatment characteristics between imipramine responders and doxepin non-responders.

Adult↗
PubMed1981

Quantitative mapping of metabolites of imipramine and desipramine in plasma samples by gas chromatographic-mass spectrometry.

Imipramine and desipramine are known to metabolize primarily by demethylation and hydroxylation. Hydroxy metabolites, 2-hydroxyimipramine and 2-hydroxydesipramine, are reported to be pharmacologically active by in vitro studies. We now report a simple gas chromatographic-mass spectrometric selected ion-monitoring (SIM) method for hydroxy metabolites of imipramine and desipramine from plasma samples using deuterated analogues as internal standards. d4-Internal standards for imipramine, desipramine, and their 2-hydroxy derivatives, were prepared in our laboratory and added to plasma samples, extracted at pH 9 with ethyl acetate, then at pH greater than 11 with hexane-isopropanol. The extracts were combined and evaporated under nitrogen. The trifluoroacetyl derivatives were prepared using N-methyl-bis-trifluoroacetamide and analyses were performed using GC-MS selected ion-monitoring in the electron ionization mode. Hydroxylation to 2-hydroxy metabolites varied widely between subjects. We also noticed in vivo methylation of desipramine to imipramine as a pathway of its metabolism in 15% of the subjects. It is suggested that plasma levels of all active metabolites must be considered in the assessment of the relationship of plasma levels of the drug to clinical response.

Biotransformation↗
PubMed1975

Influence of imipramine on the circulatory system in the course of endogenous depressive syndromes. I. Evaluation of the basic parameters of the circulatory system.

In patients with endogenous depression, imipramine exerts a regulative effect in both directions on blood pressure and pulse rate, dependent on the starting levels. In a majority of patients treated with imipramine, after 14 days blood pressure dropped and pulse rate was slowed. Remission of endogenous depression was statistically significantly more frequent in patients treated with imipramine in whom pressure and pulse rate underwent normalization. Early appearance of these effects of imipramine in patients with endogenous depression seems to be a good prognostic index.

Adult↗
PubMed1993

Adaptive changes in the N-methyl-D-aspartate receptor complex after chronic treatment with imipramine and 1-aminocyclopropanecarboxylic acid.

Chronic (14 daily injections) treatment of mice with the prototypic tricyclic antidepressant imipramine significantly alters ligand binding to the N-methyl-D-aspartate (NMDA) receptor complex. These effects were compared to a chronic regimen of 1-aminocyclopropanecarboxylic acid, a high-affinity partial agonist at strychnine-insensitive glycine receptors which mimics the effects of imipramine in preclinical models predictive of antidepressant action. Changes in the NMDA receptor complex after chronic, but not acute treatment with imipramine were manifested as: 1) a reduction in the potency of glycine to inhibit [3H]5,7-dichlorokynurenic acid binding to strychnine-insensitive glycine receptors; 2) a decrease in the proportion of high-affinity glycine sites inhibiting [3H]CGP 39653 binding to NMDA receptors; and 3) a decrease in basal [3H]MK-801 binding (under nonequilibrium conditions) to sites within NMDA receptor-coupled cation channels which was reversible by the addition of glutamate. These effects were observed in cerebral cortex, but not in hippocampus, striatum or basal forebrain. Chronic treatment with 1-aminocyclopropanecarboxylic acid resulted in changes which paralleled those of imipramine on ligand binding to the NMDA receptor complex, but the reduction in basal [3H]MK-801 binding did not achieve statistical significance. These findings indicate that adaptive changes in the NMDA receptor complex could be a feature common to chronic treatment with structurally unrelated antidepressants.

2-Amino-5-phosphonovalerate↗