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Amitriptyline and imipramine poisoning in children.

The increasing number of children admitted to this hospital with poisoning by tricyclic antidepressants is causing concern. Of 60 children admitted between January 1966 and July 1973, half were admitted in the last 18 months. In 60% of these patients the tricyclic compounds had been prescribed for nocturnal enuresis. One child aged 2 years and 4 months died of imipramine poisoning. It is imperative that all children with poisoning by tricyclic compounds, irrespective of the dosage, are admitted to hospital for continuous cardiac monitoring. Cardiac arrhythmias induced in children by amitriptyline and imipramine are prominent and dangerous.In the earlier years of this survey the antidepressants taken by children had usually been prescribed for adults, but recently they have been increasingly prescribed as a treatment for enuresis in children themselves. Medicine for a trivial complaint is unlikely to be regarded by parents as potentially dangerous and practitioners should therefore warn them accordingly; if, indeed, the transient effect of these potentially dangerous drugs upon the average case of bed-wetting in childhood can be justified.

Amitriptyline↗

Decreased platelet 3H-imipramine binding sites in classical migraine.

Patients with classical migraine investigated between attacks had significantly fewer platelet 3H-imipramine binding sites than control subjects and this finding was more marked in males than in females. There was no abnormality of binding characteristics of platelet 5-hydroxytryptamine receptors or of platelet alpha 2-adrenoceptors. Because the reduced 3H-imipramine binding capacity was found in classical migraineurs who were investigated between attacks, it may reflect a predisposition to migraine rather than being a consequence of attacks.

Blood Platelets↗

Thyroid accumulation and adverse effects of imipramine and desipramine in rats after long-term administration.

The respective adverse effects of imipramine and desipramine on serum thyroid hormone levels and their accumulation in thyroid were investigated in male Wistar rats. Two groups of 30 rats were gavaged for 4 weeks with 30 mg/kg/day imipramine hydrochloride (IMI) or desipramine hydrochloride (DESI), while the control group (12 rats) received the arabic gum vehicle only. In the IMI-treated group, the serum thyroxine (T4) level significantly decreased (by 13%) and IMI and its metabolite DESI were accumulated in the thyroid, as pointed out by mean thyroid-to-serum concentration ratios close to 12 and 8, respectively. In the DESI-treated group, the mean thyroid-to-serum concentration ratio of the drug was close to 14, and significant decreases in both serum T4 (-20%) and triiodothyronine serum levels (-14%) were found. The accumulation of antidepressant drugs in the thyroid was more pronounced and the thyroid serum levels were even lower after DESI administration than after IMI administration. These results are in favour of an antithyroid action of IMI and DESI due to the formation of a complex in the thyroid between molecular iodine and the drugs or metabolites.

Animals↗

Plasma levels of imipramine in depression. Environmental and genetic factors.

On the basis of tentative evidence obtained with 26 patients with unipolar affective illness, the variability in the response to imipramine is mostly due to interindividual differences in hydroxylating microsomal enzymes which are genetically controlled but whose activities are subject to modification by environmental factors such as overall pharmacological exposure and tobacco smoking. Additional significant pharmacodynamic variability (twofold) was found in the range of the volumes of distribution of imipramine in the patients. Clinical outcome was unequivocally related to plasma level. Unipolar nondelusional patients with levels less than 180 ng/ml had a low probability of recovery, while levels above 180 ng/ml were assoicated with a high probability of recovery. Unlike the findings of investigators working with nortriptyline, our data do not suggest an upper limit on plasma levels beyond which clinical response deteriorates. It appears that, on the basis of family studies, similar genetic characteristics are related to the ones controlling the pharmacodynamics will be the subject of further examination in our continuing studies.

Adult↗

MMPI prediction of imipramine response: a replication study.

18 hospitalized male depressives were treated with imipramine hydrochloride for 28 days. Prior to initiating treatment, each patient completed the Minnesota Multiphasic Personality Inventory (MMPI). At the end of the treatment period, the patients were divided into groups of responders and nonresponders based on the change in their Hamilton Depression Rating Scale scores. The Imipramine Response Scale - Male (IRS-M) was scored for each patient and the ability of the scale to predict response or nonresponse in our sample of patients was examined. There was no evidence that the IRS-M was better than chance in its ability to predict response.

Adult↗

CSF-MHPG in depressive syndromes: basal values and imipramine-induced modifications.

The levels of 3-methoxy-4-hydroxyphenylethylene-glycol (MHPG) in cerebrospinal fluid (CSF), before and after treatment with imipramine, were determined in 12 patients with endogenous depression. No significant change as observed in the whole group of patients, but patients with higher CSF-MHPG basal values showed better therapeutic results and a significant decrease of the norepinephrine catabolyte. The possible relevance of norepinephrine system imbalance to the therapeutic response to imipramine is discussed.

Adult↗

High affinity 3H-imipramine binding in human platelets: age and sex effects.

Age and sex effects on 3H-imipramine platelet binding sites were determined in 58 normal subjects (27 males, 31 females). The correlation of age with either the maximal imipramine binding (Bmax) or the dissociation constant (Kd) was statistically nonsignificant in both males and females. Males did not differ from females in Bmax and Kd values. The implications for psychiatric research were discussed.

Adolescent↗

A controlled double-blind study comparing binedaline and imipramine in the treatment of endogenous depression.

UNLABELLED: 50 hospitalized endogenously depressed patients (age 20-60 years, HAM-D greater than or equal to 18) were treated daily with 3 X 50 mg imipramine or 3 X 100 mg binedaline. Clinical and laboratory assessments were done before and on days 1, 3, 5, 15 and 30 of treatment. Mean Hamilton and Zung scores were statistically significant lower on day 30 when compared with pretreatment scores. No psychiatric, clinical or statistical differences were noted between the two groups. The efficacy of the clinical global impression scale was slightly higher in the binedaline groups. Frequency of side effects (specially anticholinergic) was lower in the binedaline group. CONCLUSION: binedaline is equally effective as imipramine, but with less side effects.

Adult↗

Effects of the tetracyclic antidepressant pirlindole on sensorimotor performance and subjective condition in comparison to imipramine and during interaction of ethanol.

Two experiments were designed to investigate the side-effects on motor performance of the new tetracyclic antidepressant, pirlindole, in healthy volunteers. First, pirlindole was compared with imipramine and placebo. In the second study the interaction of pirlindole with a small amount of ethanol (0.4 g 17 vol%/kg) was analysed. Ratings of subjective feelings and measurements of sensorimotor performance (simple and choice reaction, tracking) of the pirlindole-treated group did not differ from those of the placebo group, whereas imipramine caused a change of the subjective condition to more lethargy and a greater delay of the simple reaction time. The effects of pirlindole proved to be unaffected by ethanol.

Adult↗

Chronic treatment with imipramine does not reverse the effects of 3 anxiogenic compounds in a test of anxiety in the rat.

The ability of chronic treatment with imipramine (an antidepressant with anti-panic activity) to antagonise the anxiogenic effects of 3 different compounds was investigated in the elevated plus-maze. The compounds chosen are likely to produce anxiety by activity at different sites in the central nervous system: yohimbine, by blocking the alpha 2-adrenoceptor; FG 7142, by action at the beta-carboline site on the GABA-benzodiazepine receptor complex and pentylenetetrazole, by acting at the picrotoxinin site on this complex. Administration of imipramine following 21 days pre-treatment did not produce a significant consistent anxiolytic effect alone and was unable to reverse the anxiety produced by any of the 3 anxiogenic compounds. Our results are discussed in terms of the nature of the anxiety produced by the anxiogenic drugs and the sensitivity of tests of anxiety to anti-panic agents.

Animals↗

Effects of amoxapine and imipramine on evoked potentials in the Continuous Performance Test in patients with affective disorder.

Twenty patients with major depressive disorder were studied with evoked potential (EP) topographic mapping after receiving placebo, imipramine, or amoxapine for 2 days in a random-assignment, double-blind design. Patients performed the Continuous Performance Test (CPT), a visual vigilance test. The stimuli were the digits 0-9, with 0 a target to be responded to with a button press. EPs were recorded from 32 channels and were averaged separately for detected and undetected targets and for false positives and correctly identified nontargets (no button press). Twenty-one normal controls were also tested. Amoxapine enhanced N120 amplitude in midline parietal and right parietal cortex where selective attention effects have been found to be greatest in studies of normal controls. Both amoxapine and imipramine enhanced differences in P200 between target and nontarget stimuli in comparison to placebo, with amoxapine differences again being greatest over midline parietal locations. CPT performance was significantly better on amoxapine than placebo.

Adult↗

Personality features and platelet 3H-imipramine binding.

In an attempt to provide further information on the functions of the serotonergic system in humans, we investigated the possible correlation between a peripheral serotonergic marker, such as platelet 3H-imipramine binding, and the Minnesota Multiphasic Personality Inventory (MMPI) items and scales in a group of 20 healthy subjects. The results showed the presence of significant positive correlation between the maximum binding capacity, a measure of the number of 3H-imipramine sites, and 17 MMPI items suggestive of personality features of self-certainty, feeling of well-being and sense of reality.

Adult↗

Increase in serotonin 1A receptors in the dentate gyrus as revealed by autoradiographic analysis following repeated electroconvulsive shock but not imipramine treatment.

The effects of repeated treatment with electroconvulsive shock (ECS) and imipramine on [3H]8-OH-DPAT binding to serotonin1A (5-HT1A) receptors in the rat brain were studied by quantitative autoradiographic analysis. A large number of binding sites for [3H]8-OH-DPAT were observed in the hippocampus, especially the dentate gyrus, CA1+CA2 field, dorsal raphe nucleus and septum. Repeated treatment with ECS, but not repeated imipramine treatment, significantly increased [3H]8-OH-DPAT binding sites in the dentate gyrus. These results suggest that the increase in [3H]8-OH-DPAT binding sites in the dentate gyrus may be important in ECS therapy for depressive illness.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

A behavioral and autonomic nervous system study of chronic imipramine administration to conscious dogs.

The clinically effective antidepressant imipramine, an iminodibenzyl structure, was examined in two experimental methods which had previously demonstrated high prediction ability in descerning and categorizing potential psychotherapeutic drugs. The chronic administration of imipramine produced a significant reduction in the scores of aberrant behavioral response evoked by the fixed-dose with Ditran seen as early as 1 week after treatment was initiated and continuing through the 8-week treatment duration. This chronic per oral treatment with impramine was also associated with a significant potentiation of mean arterial pressure responses to fixed-dose treatment with serotonin, noradrenaline, yohimbine and adrenaline, while significantly inhibiting the histamine-induced depressor response. The results of this study support the speculation that, in dogs, the clinically effective antidepressants antagonize or reverse the Ditran-induced response and produce an associated response of sympathetic nervous system arousal or sensitization.

Animals↗

Comparative side effect profiles of trazodone and imipramine: special reference to the geriatric population.

Side effects are a concomitant of almost all therapeutic agents and are also present as part of the pharmacological profile of psychotropic agents. However, the laboratory pharmacological characteristics of agents are a more reliable predictor of side effect profiles than they are of their therapeutic activities. Therefore, it would seem possible to be able to predict with much greater accuracy the clinically significant side effects that may be encountered from the preclinical data. This has been established in the case of trazodone and imipramine. The anticholinergic profile of imipramine was clearly determined in the laboratory and in man it produces a range of activity varying from mild peripheral anticholinergic activity to impairment of various functions involving vision, cardiovascular function and gastrointestinal activity. However, in the geriatric population, because of the vast amount of research implicating cholinergic mechanisms in memory functions and particularly in some aspects of cognitive deficit, it may be predicted that the anticholinergic activity of the tricyclics may present an especially troublesome pattern in a geriatric population that requires antidepressant therapy. These comparative effects between the two agents will be discussed and documented from control study data.

Aged↗

Use of imipramine in children with intractable asthma and psychiatric disorders: a warning.

Imipramine is an established treatment for anxiety in adults. Some evidence also exists that it may be beneficial in children. Because of the frequent co-occurrence of anxiety and affective symptomatology in asthmatic children, a pilot study was undertaken to obtain clinical observations on the effects of imipramine on symptoms of asthma as well as those of separation anxiety and depression in children suffering from intractable asthma. The pilot trial was terminated because of medical complications after 6 patients participated.

Adolescent↗

Sex-related hyperthermic response to chlorpromazine in the offspring of rats treated with imipramine.

The body temperature in male rats born to mothers treated with saline or imipramine (5 mg/kg, IMI-F1) from day 1 to day 21 of gestation showed a significant decline between 8 and 13 weeks of age. The magnitude of the decline was greater in the IMI-F1 rats than in saline-F1 rats. In contrast, the body temperature in the IMI-F1 female rats showed a significant rise between 8 and 13 weeks of age. Adult IMI-F1 male rats showed a significant hyperthermia for 1-2 h after an injection of chlorpromazine while the littermate female rats and the control male and female rats showed a marked hypothermia. The results suggest that prenatal exposure to imipramine induces sex-related alterations in the thermoregulatory centers.

Animals↗