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At least 433 records · Page 24Linked to original sources
PubMed1984

Phenelzine v imipramine in atypical depression. A preliminary report.

Sixty patients meeting specific criteria for atypical depression completed six weeks of double-blind, randomly assigned treatment with phenelzine sulfate, imipramine hydrochloride, or placebo. The overall response rates were 67% with phenelzine, 43% with imipramine, and 29% with placebo. At week 6, phenelzine was superior to placebo on many measures, while the superiority of imipramine to placebo was confined to several variables. Phenelzine was superior to imipramine on the interpersonal sensitivity and paranoia factors of the 90-item Hopkins Symptom Checklist, with trends toward superiority on several other measures, while imipramine was not differentially superior on any measure. Atypical depressive patients with a history of spontaneous panic attacks and hysteroid dysphoric patients both showed extremely low rates of response to placebo and high rates of response to phenelzine. Conversely, those without panic or hysteroid dysphoric features responded equally to all three treatments. Responders to pheneizine also had greater platelet monoamine oxidase inhibition while receiving drug therapy than did nonresponders. Completion of the 120-patient sample will allow more detailed analyses.

Adolescent↗
PubMed1985

Noradrenergic function and the mechanism of action of antianxiety treatment. II. The effect of long-term imipramine treatment.

Considerable preclinical and clinical evidence indicates that increased noradrenergic function is involved in the development of anxiety. Imipramine hydrochloride, which has complex effects on noradrenergic function in animals, is effective in patients with agoraphobia and panic disorder. To assess the effects of imipramine on noradrenergic function in patients, plasma levels of free 3-methoxy-4-hydroxyphenylglycol (MHPG) and yohimbine-induced increases in plasma MHPG levels, anxiety-nervousness, blood pressure, and somatic symptoms were studied before and during long-term imipramine treatment in 11 patients meeting DSM-III criteria for agoraphobia with panic attacks. Long-term imipramine treatment significantly decreased baseline plasma MHPG levels by 38% and modestly potentiated yohimbine-induced increases in blood pressure, but it did not alter yohimbine-induced increases in plasma MHPG levels or in patient ratings of anxiety-nervousness. The therapeutic effects of imipramine in panic disorder may relate more to the decrease in norepinephrine turnover than to alterations of alpha 2-adrenergic autoreceptor function.

Adult↗
PubMed1989

Autoradiographic analysis of tritiated imipramine binding in the human brain post mortem: effects of suicide.

In vitro quantitative autoradiography of high-affinity tritiated imipramine binding sites was performed on brains of 12 suicide victims and 12 matched controls. Region-specific differences in imipramine binding were found between the two groups. Thus, the pyramidal and molecular layers of the cornu ammoni hippocampal fields and the hilus of the dentate gyrus exhibited 80%, 60%, and 90% increases in binding in the suicide group, respectively. The postcentral cortical gyrus, insular cortex, and claustrum had 45%, 28%, and 75% decreases in binding in the suicide group, respectively. No difference in imipramine binding was observed in prefrontal cortical regions, in the basal ganglia, and in mesencephalic nuclei. No sex and postmortem delay effects on imipramine binding were found. Imipramine binding was positively correlated with age, the effect of age being most pronounced in portions of the basal ganglia and temporal cortex.

Adolescent↗
PubMed1999

Long-term maintenance and discontinuation of imipramine therapy in panic disorder with agoraphobia.

BACKGROUND: There has been little systematic work done regarding the long-term treatment of panic disorders. The aim of the present study was to assess the 12-month cumulative risk of relapse specifically due to discontinuation of imipramine and to test the hypothesis that maintenance treatment with imipramine protects patients with panic disorder and agoraphobia from such reversals. METHOD: Following an acute-phase open trial with imipramine (2.25 mg/kg per day) involving 110 patients for 6 months, the 56 patients who were in stable remission, did not require additional treatment, and consented to be randomly assigned to double-blind maintenance (n = 29) or discontinuation (n = 27) conditions were followed up with planned assessments every 2 months during a 1-year period. There were no behaviorally oriented interventions or instructions at any time during the 18 months of the study. RESULTS: Maintenance treatment (1 relapse) and discontinuation (10 relapses) conditions had significantly different survival curves (Mantel-Cox statistic chi(2)1 = 10.47, P = .001). None of the additional 10 variables from demographic, clinical, and open-treatment domains considered in the proportional hazard model disrupted the significant relationship between experimental drug condition and relapse; other things being equal, a patient receiving imipramine maintenance was 92.5% lower in the hazard rate of relapse than a patient receiving placebo. CONCLUSION: The results confirm the very high degree of prophylactic effectiveness of maintenance imipramine treatment and demonstrate that relapse, although substantial, occurs in a minority of patients with panic disorder and agoraphobia who are in stable remission prior to treatment discontinuation.

Adult↗
PubMed2004

In vitro microsomal metabolism of imipramine under conditions mimicking the in vivo steady-state situation.

A steady-state model is presented of the metabolism of imipramine. In this model, the N-demethylation and 2-hydroxylation rates of imipramine were measured with and without the presence of metabolites by using a tritium isotope of imipramine. At an imipramine concentration of 5 micromol/l, desipramine, in the concentration ratio 1:2, decreased the total metabolic rate by 70%. The 2-hydroxylation pathway was mainly inhibited, thereby increasing the N-demethylation pathway from 25% to 62% in the presence of desipramine. The additional presence of 2-hydroxy-imipramine did not change this situation. A study on the relative influence of CYP1A2 and 3A4 only revealed minor changes in the presence of desipramine. In conclusion, the presence of metabolites in metabolism studies undertaken in vitro may reflect the changes from the single- to the multiple-dose situation observed clinically and therefore constitute a better model for the clinical application of a drug.

Cytochrome P-450 Enzyme System↗
PubMed1986

Imipramine prevention of carbon tetrachloride-induced liver necrosis at late states of the intoxication process.

Imipramine administration (50 mg kg-1, i.p.) to Sprague-Dawley male rats (240-290 g) 6 or 10 h after CCl4 (1 ml kg-1, i.p.) partially prevents liver necrosis induced by the hepatotoxin. When imipramine is given 30 min before CCl4, it inhibits in part the CCl4-induced lipid peroxidation and the covalent interactions of reactive metabolites with microsomal lipids or proteins and partially prevents CCl4-induced cytochrome P-450 destruction, but not glucose 6 phosphatase activity depression. Imipramine administration prior to CCl4 does not modify levels of the hepatotoxin reaching the liver or the body temperature of CCl4 treated animals. Early preventive effects of imipramine on cytochrome P-450, might be attributed to inhibition of covalent interactions of reactive metabolites. The hypothesis that imipramine exerted late preventive effects by interfering with calcium deleterious effects or by modulation of protein and phospholipid synthesis or degradation is analyzed.

Animals↗
PubMed1998

Inhibition by imipramine of ATP-evoked responses in rat pheochromocytoma cells.

The effect of imipramine on the ATP-evoked release of dopamine was analyzed in parallel with its effects on the rise in the intracellular Ca2+ concentration ([Ca2+]i) and current induced by ATP in rat pheochromocytoma PC12 cells. Imipramine (10-300 microM) inhibited the ATP-evoked release of dopamine and rise in [Ca2+]i in a concentration-dependent fashion though the effect of imipramine on the release was slightly more obvious. Imipramine also inhibited the ATP-activated inward current at a similar concentration range. These results show a new pharmacological profile of imipramine, namely the inhibition of P2X2 receptors.

Adenosine Triphosphate↗
PubMed1991

Differential effects of ovarian steroid hormones on beta-adrenoceptor downregulation caused by the antidepressants imipramine and rolipram.

Downregulation of beta-adrenoceptors in response to repeated administration of imipramine or rolipram was investigated in the brain of pregnant rats and ovariectomized animals treated with estrone, progesterone or a combination of both hormones. Ovariectomy alone was without influence on drug responses. Pregnancy and complete hormone replacement of animals prior to drug treatment halved the response to imipramine and obliterated that to rolipram. Administration of only estrone to ovariectomized rats did not affect the extent of adrenergic downregulation caused by imipramine, but fully suppressed the rolipram action. Castrated males with or without treatment with estrone and progesterone were used as further controls. Castration alone diminished the effects of both antidepressants. Treatment of gonadectomized rats with both ovarian steroid hormones voided the actions of rolipram. The data indicate that imipramine and rolipram share a common pathway for their mechanism of action which can be attenuated by ovarian steroid hormones. In addition, imipramine has a second major site of action which is not subject to modulation by female steroids.

Animals↗
PubMed1987

Analysis of the nature of antagonism of the reserpine-induced hypothermia by imipramine.

Antagonism of reserpine-induced hypothermia is an animal model used in the screening of antidepressants. The activity of imipramine on this test is partly impaired by propranolol. This effect of imipramine was analyzed using specific adrenoceptor and 5-HT receptor blocking drugs in order to determine the nature of this effect of propranolol. The non-selective beta 1-beta 2 adrenoceptor antagonist, propranolol as the specific beta 1 adrenoceptor antagonist betaxolol, but not the specific beta 2 blocking drug DL-erythro-3-isopropylamino-1-(7-methyl-4-indanyloxy)-2-butanol hydrochloride 313.9 (ICI 118,551), partly antagonized the effect of imipramine at 30 min. None of the serotonin (5-HT) receptor antagonists, methysergide, metergoline, ritanserin and buspirone, impaired the effect of imipramine. On the contrary, methysergide alone antagonized reserpine-induced hypothermia and methysergide or metergoline increased the action of imipramine. Propranolol impaired neither the hypothermia induced by an agonist at the 5-HT 1A receptors: 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) nor the increase in spontaneous motor activity induced by an agonist at the 5-HT 1B receptors: 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1-H indole (Ru 24,969). It is concluded that the effect of propranolol is not the result of a blockade of 5-HT 1A, 5-HT 1B or 5-HT 2, but is in part due to blockade of beta 1 adrenoceptors.

Adrenergic beta-Antagonists↗
PubMed1980

Imipramine and REM sleep: cholinergic mediation in animals.

To date it has not been established whether the anticholinergic properties of imipramine are responsible for the drug's suppresion of REM and prolongation of REM induction. A cholinesterase inhibitor, physostigmine, was administered in conjunction with imipramine to determine if these effects of imipramine were cholinergically medicated. Sleep EEG recordings were observed in rats administered either physostigmine (1.0 mg/kg), or imipramine (1.25, 2.5 or 5.0 mg/kg), alone or in combination. The results indicate that physostigmine blocks the effects of imipramine on REM latency.

Animals↗
PubMed1977

Effects of chlorpromazine and imipramine on discrimination learning, consolidation, and learned behavior in two inbred strains of mice.

Chlorpromazine and imipramine were administered to DBA/2J and C57BL/6J mice swimming in a Y water maze toward a light source (L Procedure, corresponding to innate tendency) or towards the dark (D Procedure, corresponding to the acquisition of a new pattern of behavior). In two sets of experiments the drugs were administered to naive mice before and after each training session, respectively. In both strains, in the pretrial experiments, the innate tendencies were improved by both drugs; the acquisition of a new pattern of behavior was improved following imipramine but impaired following chlorpromazine. In the posttrial experiments (D procedure) the consolidation processes of both strains were improved following imipramine and impaired following chlorpromazine. In a third set of experiments imipramine was administered to previously trained mice of both strains and chlorpromazine to previously trained C57 mice. In both procedures the administration of increasing doses of both drugs was followed by a progressive lenghtening of the swimming times in the previously trained C57 mice; performance disruptions were evident in both procedures in trained DBA mice mice following imipramine.

Animals↗
PubMed1975

The effect of amitriptyline, desipramine and imipramine on the vivo brain synthesis of 3H-noradrenaline from 3H-L-dopa in the rat.

3H-L-Dopa was given to rats after a peripheral decarboxylase inhibitor Ro 4-4602 (50 mg/kg) and the effect of 30 min pretreatment with antiptyline (10 mg/kg), desipramine (10 mg/kg) and imipramine (10 mg/kg) on the brain formation of 3H-dopamine, 3H-noradrenaline and their major metabolites was investigated. Desipramine produced a decrease in the level of labelled noradrenaline and its major metabolites free and conjugated 3-methoxy-4-hydroxyphenyleneglycol and 3,4-dihydroxyphenyleneglycol. Imipramine decreased labelled noradrenaline and 3-methoxy-4-hydroxyphenyleneglycol, whereas amitriptyline produced no significant effect on noradrenaline metabolism. The thymoleptic drugs produced no significant effect on endogenous brain noradrenaline and dopamine. These findings provide a strong indication that desipramine and imipramine inhibit the 3H-noradrenaline biosynthesis from 3H-L-Dopamthe effect seems closely related to the well-known membrane inhibitory effect of these drugs, since desipramine produced a more marked effect than imipramine and amitriptyline showed no effect. No conclusive evidence for the precise mechanism of action was obtained but it is possible that the decreased 3H-noradrenaline synthesis is related to interference of desipramine and imipramine with the precursor (s) 3H-L-Dopa or 3H-dopamine at sites of 3H-noradrenaline biosynthesis.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

Cardiovascular effect of imipramine and nortriptyline in elderly patients.

Cardiovascular effects in elderly depressed patients (age 62-78 years) treated with imipramine (N = 11) or nortriptyline (N = 10) were recorded by monitoring of heart rate, blood pressure, systolic time intervals, standard ECG and 24-h ECG. The two drugs exhibited distinctly different cardiovascular reactions. The use of imipramine was severely limited by orthostatic hypotension occurring at subtherapeutic plasma levels, which resulted in falls with fracture in two patients. In contrast, nortriptyline at therapeutic drug levels did not significantly influence orthostatic blood pressure regulation. Nortriptyline caused moderate changes in systolic time intervals, indicating impairment in myocardial contractility. This effect was not seen with imipramine, but a majority of the patients did not reach therapeutic plasma levels because of blood pressure reactions. Neither imipramine nor nortriptyline induced changes in cardiac conduction time measurements or arrhythmias. In addition to the blood pressure reactions, the use of imipramine was complicated by dose dependent kinetics.

Aged↗
PubMed1982

3H-imipramine binding and serotonin uptake in platelets from untreated depressed patients and control volunteers.

Human platelets possess specific high-affinity binding sites for 3H-imipramine which have similar characteristics to the sites previously described in human and animal brain. In a group of untreated depressed patients, the Bmax of 3H-imipramine binding and the Vmax of serotonin uptake in their platelets were found to be significantly lower than in a group of control volunteers. There was no significant difference in the Kd values for 3H-imipramine binding but the Km values of 3H-serotonin uptake were decreased in the depressed patients. When the measurements of 3H-imipramine binding and 3H-serotonin uptake were compared in the same individual, however, there was no correlation between the individual Bmax and Vmax values or the Kd and Km values. These results suggest that although the 3H-imipramine binding site and the mechanism for serotonin uptake are associated, they are not identical.

Adult↗
PubMed1981

High-affinity 3H-imipramine binding in platelets from untreated and treated depressed patients compared to healthy volunteers.

Specific high-affinity binding of 3H-imipramine to human platelets possesses very similar characteristics to the sites previously described in animal and human brains. In a study comparing the binding of 3H-imipramine in platelets obtained from 39 control volunteers with 37 hospitalized, untreated, severely depressed patients, the maximal binding of 3H-imipramine was found to be significantly lower in the depressed population. There were no differences in the KD values. After 7-15 days of treatment with tricyclic anti-depressant drugs, there was an improvement in the degree of the depression but no significant change in the maximal 3H-imipramine binding. After an average of 50 days treatment, Hamilton ratings had returned to normal, but the 3H-imipramine binding values remained unchanged.

Adult↗
PubMed1984

The effect of imipramine and desipramine on mixed function oxidase in rats.

The effects of imipramine and desipramine on hepatic mixed function oxidase were measured in male Wistar rats. Both antidepressants increased hepatic cytochrome P-450 when given b.i.d. for 7 or 14 days. In vitro demethylation of imipramine was rather depressed than increased. 14CO2 exhalation from [N-methyl-14C] benzphetamine was increased by pretreatment with the antidepressants as well as with phenobarbital, but imipramine had no influence on the exhalation of the label from [6-methoxy-14C]- or [7-methoxy-14C]-scoparone. No difference was observed between treatment with imipramine or desipramine. It is concluded that changes of the demethylation rate of imipramine are not responsible for its delayed elimination observed after chronic treatment (Daniel et al. 1981).

Animals↗
PubMed1985

Treatment of haemodynamic and electrocardiographic side-effects resulting from imipramine toxicity in rats and dogs.

This study was designed to analyze the effects of carbocromene and dipyridamole on the haemodynamic and electrocardiographic side-effects resulting from imipramine infusion in anaesthetised rats and dogs. Imipramine was infused at 1 mg/kg/min until cardiac failure and vascular collapse terminated the experiment at 21 +/- 2.3 min in rats and at 29.5 +/- 2.1 min in dogs. This was characterized by hypotension, bradycardia, intraventricular conduction delay, cardiac tachyarrhythmia and A-V block. Carbocromene (4 mg/kg i.v., followed by 80 micrograms/kg/min) protected the animals against heart failure. This was associated with delayed hypotension and negative inotropy, and lower incidence of heart block. Survival time increased to 37 +/- 1.5 min (P less than 0.05), and 54.2 +/- 2.6 min (P less than 0.02) in rats and dogs, respectively. Dipyridamole (0.5 mg/kg i.v., followed by 80 micrograms/kg/min) failed to decrease imipramine toxicity as judged by the haemodynamic and electrocardiographic parameters and did not alter survival time of imipramine controls. These results suggest that carbocromene is an effective treatment for imipramine-induced cardiovascular collapse and cardiac arrhythmias, the beneficial effects being largely due to metabolic and membrane stabilizing effects. Carbocromene has both therapeutic and prophylactic value and appears to be superior to dipyridamole therapy.

Animals↗
PubMed1989

Imipramine treatment in diabetic neuropathy: relief of subjective symptoms without changes in peripheral and autonomic nerve function.

The effect of imipramine on symptomatic peripheral diabetic neuropathy in 9 patients was examined in a double-blind cross-over study against placebo. The dose of imipramine was adjusted to yield optimal plasma levels of imipramine plus desipramine of 300-750 nM. Imipramine had a clear beneificial effect on the symptoms of the neuropathy, whereas no changes in a range of neurophysiological measurement was detected. Despite some adverse effects, especially of an anticholinergic nature, the patients generally preferred imipramine to placebo.

Adult↗