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Magical thinking and imipramine poisoning in two school-age children.

Two young school-aged boys took an overdose of imipramine hydrochloride to help their enuresis. One child died, and the other required resuscitation. An office survey found that one third of school-aged children did not realize the potentially hazadous consequences of taking extra amounts of prescription medications. Physicians might be able to prevent similar needless tragedies by warning both the child and the parents of the unusual lethality of imipramine and other dangerous prescription drugs.

Accidents, Home↗

The influence of chlorpromazine, diazepam and imipramine on the central action of ethanol.

In experiments with white rats, chlorpromazine, diazepam and imirpramine injected intraperitoneally in the dose of 20 mg/kg and imipramine and diazepam in the dose of 50 mg/kg did not enhance the acute toxicity of ethanol expressed as LD50. Only chlorpromazine in the dose of 50 mg/kg i.p. increased toxicity of ethanol. However, the aforementioned drugs intensified the central action of ethanol by prolonging (except imipramine) duration of narcotic sleep and motor incoordination, and potential ethanol-induced hypothermia.

Animals↗

Response of postpsychotic depression to adjunctive imipramine or amitriptyline.

Case histories were reviewed of 25 patients with RDC diagnoses of schizophrenia or schizoaffective disorder who developed a clinical syndrome of depression subsequent to the resolution of their psychotic episodes. Of these patients, 14 were then treated with imipramine and 11 with amitriptyline in addition to their neuroleptic drugs. As a group, the patients did well--48% had a remission of depressive symptoms and an additional 32% improved. Psychotic exacerbation was noted in only one patient. Imipramine seemed more beneficial than amitriptyline in these patients.

Adult↗

Quaternary ammonium-linked glucuronides of amitriptyline, imipramine, and chlorpromazine.

The quaternary ammonium-linked glucuronides of amitriptyline, imipramine, and chlorpromazine were shown to be conjugated in vitro using an immobilized rabbit hepatic microsomal enzyme preparation. It was shown that fast atom bombardment mass spectrometry could be used for direct characterization of these involatile, thermally labile metabolites. The quaternary ammonium-linked glucuronides of amitriptyline and imipramine were demonstrated to be present in urine from patients receiving therapeutic doses of these tricyclic antidepressants.

Amitriptyline↗

A two-center double-blind study of nomifensine, imipramine, and placebo in depressed geriatric outpatients.

Both nomifensine and imipramine were superior to placebo in a 4-week double-blind study involving 63 geriatric patients (greater than 60 years) with primary affective disorder-depression. Significant improvement in the active drug groups was demonstrated on the Hamilton Depression Rating Scale, Clinical Global Impressions, Brief Psychiatric Rating Scale, and Hopkins Symptom Check List. Analysis of laboratory and physical examination data, including ECGs, revealed no clinically significant changes associated with either drug. Compared to the imipramine group, nomifensine-treated patients showed a more rapid rate of improvement and a lower incidence of discomforting side effects.

Aged↗

Effects of imipramine, nitrite, and dimethylnitrosamine on reproduction in mice.

Administration of the tricyclic dibenzazepine drug imipramine, a tertiary amine, in the food (100 mg/kg) or sodium nitrite (1 g/liter) or dimethylnitrosamine (0.1 ppm) in the drinking water of Swiss CD-1 mice before and during pregnancy, resulted in increased perinatal death of the offspring compared to controls. Administration of imipramine and nitrite together had no effect on perinatal survival, but instead resulted in infertility or delayed impregnation in some females. A biological synergism or in vivo chemical interaction of the two chemicals is suggested.

Animals↗

3H-imipramine platelet binding sites in unipolar depression.

High-affinity 3H-imipramine binding to platelets was determined in 15 drug-free unipolar depressed women and 15 normal controls. The maximum number of binding sites (Bmax) was lower in the depressed population, but the difference fell short of statistical significance (p = 0.07). The dissociation constant for imipramine binding (Kd) was found to be significantly lower among patients than in controls (p = 0.02). The various factors that can affect the in vitro platelet assay, and the implications for affective disorder research, were discussed.

Adult↗

The effect of lithium, imipramine and chlorpromazine on the membrane bound enzyme phosphatidylethanolamine methyltransferase.

The activity of phosphatidylethanolamine methyltransferase (PMT) in disrupted human erythrocytes and ghost cells was inhibited by lithium (Li+), imipramine and chlorpromazine. There was no inhibitory effect of the drugs in concentrations similar to the average therapeutic blood levels. Li+ exerted an inhibition on PMT activity in hemolysates at concentrations 8 times the average therapeutic level whereas chlorpromazine and imipramine showed an inhibitory effect on PMT in hemolysates at 10(3) fold their respective therapeutic serum level.

Chlorpromazine↗

Imipramine binding in subpopulations of normal human blood platelets.

Imipramine binding was studied in platelet membranes isolated with different proportions of heavy (young) and light (old) platelets. The Bmax, a measure of the number of binding sites, was greater in the heavier platelets than in the light platelets. However, the dissociation constant Kd (a reflection of the affinity of imipramine binding) was greater in the lighter platelets compared to the heavy platelets. These results indicate that differences in Kd and Bmax in particular membrane preparation, could be due to the differences in the relative proportion of heavy and light platelets.

Blood Platelets↗

Imipramine and desipramine plasma levels: relationship to dosage schedule and sampling time.

Tricyclic antidepressant plasma levels were determined after administration if imipramine (11 patients) and desipramine (ten patients) as a single daily bedtime dose or in divided doses. Plasma levels of the tricyclics were relatively stable on both dosage schedules due to the long plasma half-lives of these drugs. No difference was found between the two dosage schedules and the therapeutic effectiveness or the severity of side effects. The majority of patients preferred the single dose schedule. These findings support the use of a single daily dose of imipramine and desipramine.

Adult↗

Imipramine-induced tremor: effects of a beta-adrenergic blocking agent.

Assessment of an elderly depressed patient with an imipramine-induced tremor led to the conclusions that imipramine tremor (1) can be severe and incapacitating, (2) is most pronounced early in the treatment, (3) does not seem to be dose-related, and (4) is readily reversible with a beta-adrenergic blocking agent.

Depressive Disorder↗

[Effect of imipramine-like antidepressants on head shaking induced by 5-hydroxytryptophan in mice].

In the reaction of head twitching (HT) in mice in response to 5-oxytryptophan administration in the capacity of a serotonergic model antidepressants chlorimipramine and imipramine and also chlorpheniramine (suprastin) expressed a serotonopositive action in doses of 1.0, 5,0, and 1.0 mg/kg, respectively. Quiprazine produced a serotonomimetic action. Desipramine exerted abmivalent activity in doses of 1.0--20.0 mg/kg, whereas iprindol and morphaphen were ineffective in doses up to 20.0 mg/kg. Amitriptyline, noveril, melitracene, trimipramine, and ludiomil inhibited HT in doses of from 0.5, 1.0, 20.0, 20.0, and 20.0 mg/kg, respectively. The results are discussed in the light of the concept on the complex "neurotransmitter activity" spectrum of imipramine-like antidepressants.

Animals↗

Maprotiline versus imipramine and placebo in neurotic depression.

The antidepressant effect of maprotiline, a tetracyclic compound, was compared with that of imipramine in a four-week, double-blind, placebo controlled study with neurotic depressives. On all factors of the Hamilton Depression Rating Scale and on most items of the Zung Self-Rating Scales for Depression and Anxiety, maprotiline appeared slightly more effective than imipramine and showed a faster onset of action. In addition, it appeared to cause fewer anticholinergic side effects.

Adolescent↗

The effect of amoxapine and imipramine on serum prolactin levels.

The effect of traditional tricyclic antidepressants on serum prolactin levels is controversial. In a five-week double-blind study of depressed outpatients, imipramine hydrochloride therapy did not lead to any significant change in serum prolactin levels. In contrast, amoxapine, a new antidepressant, produced significant elevations in serum prolactin levels in female and in male patients. Amoxapine may block dopamine receptors in central tuberoinfundibular pathways, which would account for its prolactin-elevating activity. On the other hand, imipramine and other traditional tricyclic antidepressants do not affect dopamine transmission, do not raise serum prolactin levels, and are not effective antipsychotic drugs.

Adult↗

[Imipramine and neuro-psychiatry. Retrospective study of 557 out-patients treated in a neuro-psychiatric unit (author's transl)].

A retrospective study of 557 outpatients who had been treated with imipramine has been undertaken in a neuro-psychiatric unit. The usual dose was 75 mg per day, most often associated with other psychotropic drugs. The main indication was a depressive state for 75 p. c. of the patients: in that case the efficacy reached 65 p. c. The achievement of such results with moderate doses might indicate a possible relationship between the optimal dosage of the antidepressive drug and the intensity of the mood disorder. 12.5 p. c. of the patients were treated for a post-contusional syndrome. The best results have been obtained with early treatment when patients didn't have any loss of consciousness at the time of their contusion. The other successful indications of imipramine were phobic and hypocondriacal neurotic symptoms and functional headaches which were resistant to the usual treatments, raising the problem of a possible masked depression.

Adolescent↗

[Prolonged high plasma imipramine levels after acute intoxication (author's transl)].

A case of severe intoxication by tricyclic antidepressants with persistence during 14 days of abnormally high plasma imipramine levels is reported. The various factors capable of maintaining plasma imipramine at a high level are discussed. They include mechanical factors (intestinal absorption), ventilation under positive end-expiratory pressure, alterations of hepatic metabolism by other drugs such as metronidazole or cimetidine, and changes in tissue distribution. Attention is drawn to the risks inherent in the various treatments used against acute intoxications and in combined chemotherapy during intensive care generally. When such drugs are necessary, the plasma levels of those with higher toxicity should be monitored.

Adult↗

Differential effects of trazodone and imipramine on intracardiac conduction in the anesthetized dog.

Intra-atrial, ventricular septal and left ventricular free wall conduction rates as well as lead II EKG intervals and heart rate were measured in pentobarbital-anesthetized, open-chest dogs given increasing doses of either trazodone (0.3-30 mg/kg) or imipramine (0.1-10 mg/kg) intravenously. Conduction intervals were measured during periods of spontaneous nodal rhythm or fixed rate (150 b/min) of atrial pacing. Trazodone, at cumulative doses up to 44.3 mg/kg, did not significantly depress any measured index of cardiac conduction but did lower heart rate (36%) and prolong the Q-Tc interval (19%). Imipramine, particularly at doses of 3 and 10 mg/kg, caused bradycardia (32%) and significantly slowed both atrial (23-46%) and ventricular (21-55%) conduction as well as repolarization interval (14-35%). The data indicate the differing effects of these two compounds on the heart and represent suggestive evidence of the potentially greater safety of trazodone as a new and structurally distinct antidepressant drug.

Anesthesia↗