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At least 1,207 records · Page 67Linked to original sources
PubMed1980

Single-dose kinetics predict steady-state concentrations on imipramine and desipramine.

Single-dose prediction of ultimate steady-state concentrations of tricyclic antidepressants at the outset of treatment can be a valuable therapeutic tool that has had only limited application. We demonstrate accurate steady-state predictions following both the tertiary amine, imipramine hydrochloride, and the secondary amine, desipramine hydrochloride, in a carefully monitored long-term treatment patient population. Results show that long-term treatment does not alter metabolism of either imipramine or desipramine. The relative merits of single-dose predictions using total and "abbreviated" areas under the curve and concentration at 24 hours are compared. These findings demonstrate that single-dose prediction can be used as a practical therapeutic, as well as, research tool.

Adolescent↗
PubMed1983

Imipramine and brief therapists-aided exposure in agoraphobics having self-exposure homework.

Forty-five chronic agoraphobics were randomly assigned to treatment by placebo or imipramine in doses up to 200 mg/day for 28 weeks. All patients also had systematic self-exposure homework with an instruction manual. In addition, half of each drug group had therapist-aided exposure and half had therapist-aided relaxation, each totalling three hours. Patients in both drug groups improved substantially and maintained their gains for one year of follow-up. Imipramine had no significant therapeutic effect despite satisfactory plasma levels and significant drug side effects. Patients' low initial Hamilton depression scores might explain the absence of any drug effect. Antidepressants may be ineffective for agoraphobics who have normal mood. Brief therapist-aided exposure improved phobias and panics to a significant but limited extent, and is a useful adjuvant to self-exposure homework, which can be a powerful therapeutic agency by itself.

Adult↗
PubMed1983

Panic-induced elevation of plasma MHPG levels in phobic-anxious patients. Effects of clonidine and imipramine.

Six subjects with the phobic-anxiety syndrome were treated in a controlled, crossover trial of clonidine hydrochloride v imipramine hydrochloride for periods of four weeks each. During each drug trial and during baseline placebo treatment, each patient exposed himself or herself to a situation that previously elicited panic attacks. Self-rated anxiety and plasma levels of 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) were measured to study the effect of the drug treatments on noradrenergic activity and anxiety. Plasma MHPG level correlated highly with rated anxiety under all conditions, and was consistent with significant symptom reduction by clonidine or imipramine. Diminished suppression of plasma MHPG concentrations in two subjects was associated with the continued emergence of panic symptoms in response to phobic stimuli.

Adult↗
PubMed1985

Tritiated imipramine binding distinguishes among subtypes of depression.

We studied 45 depressed patients and 20 healthy controls in order to determine if tritiated imipramine binding distinguished among subtypes of primary major depressive disorder. Mean (+/- standard deviation) values for maximal concentration of tritiated imipramine binding sites on platelet membranes were significantly lower in patients with bipolar and familial pure depressive disease (754 +/- 149 and 870 +/- 241 femtomoles [fmole]/mg of protein, respectively) than in patients with depressive spectrum and sporadic depressive disease (1,236 +/- 241 and 1,188 +/- 325 fmole/mg of protein, respectively), neither of which differed from healthy controls (1,238 +/- 201 fmole/mg of protein). Multiple linear regression analysis revealed that these differences could not be attributed to differences in age, sex, Hamilton Rating Scale score, presence of psychotic features, hospitalization status, or medication history. This association of a biological finding with distinct clinically defined subtypes of depression may lead to a classification of affective disorders useful in further research.

Adult↗
PubMed1989

Relevance of DMS-III depressive subtype and chronicity of antidepressant efficacy in atypical depression. Differential response to phenelzine, imipramine, and placebo.

One hundred ninety-four nonmelancholic depressed outpatients with features of atypical depression took part in a 6-week randomized trial of imipramine hydrochloride, phenelzine sulfate, and placebo. Their courses of illness were also rated for chronicity. Significantly more patients responded to phenelzine (71%) than to imipramine (48%), which benefited significantly more patients than placebo (26%). Both chronicity and DMS-III diagnosis predicted response on several outcome measures. For example, patients with dysthymic disorder responded better to treatment than did those with major depression, suggesting that dysthymic disorder can be treated with medication. Placebo response correlated inversely with chronicity, regardless of DMS-III diagnosis. Atypical depression and longitudinal course of illness may add to the usefulness of DMS-III depressive diagnosis as a predictor of antidepressant response.

Adolescent↗
PubMed1990

Atypical depression, panic attacks, and response to imipramine and phenelzine. A replication.

In an initial study with 120 patients with reactive mood and associated atypical symptoms, phenelzine sulfate was superior to imipramine hydrochloride and placebo. Since their response to phenelzine appears to be unique, this suggests that atypical depression may be a distinct subgroup of unipolar depressive illness. Unexpectedly, the benefit of antidepressants was limited to patients who also had spontaneous panic attacks. To help establish the validity of this syndrome, a new sample of 90 atypical depressives was studied. The clinical and demographic characteristics of the original and replication sample were virtually identical at baseline. In addition, the treatment response with either placebo, imipramine, or phenelzine was also indistinguishable in the two patient groups. The outcome in the replication study supports the hypothesis that this may be a distinct unipolar depressive subgroup. In the replication sample, a history of panic attacks did not appear to be a relevant predictor. We discuss the explanations for this discrepancy in the two patient samples.

Anxiety Disorders↗
PubMed1991

Response to phenelzine and imipramine in placebo nonresponders with atypical depression. A new application of the crossover design.

We employed a study design that permitted a double-blind 12-week contrast of imipramine hydrochloride and phenelzine sulfate therapies in patients who met Columbia University criteria for atypical depression and were unresponsive to 7 weeks of treatment with placebo. These patients were found to benefit selectively from therapy with monoamine oxidase inhibitors compared with tricyclic drug therapy. This supports our observation about treatment response in depressed patients with reversed vegetative features. The design we utilized in this study has not previously been reported, to our knowledge. It was hypothesized that it would offer the advantage of the removal of a portion of placebo responders and serve to replicate our original findings. Treatment response to therapy with both imipramine and pheneizine in placebo nonresponders was uniformly lower (roughly 20% less than corresponding rates for patients who did not participate in the initial 6-week placebo trial). This is consistent with the view that the lower response rates were a result of the removal of some "placebo" responders in the drug groups. We think this is a useful design that should be considered in all studies of placebo and two active treatment regimens.

Adult↗
PubMed1999

The antidepressants imipramine, clomipramine, and citalopram induce apoptosis in human acute myeloid leukemia HL-60 cells via caspase-3 activation.

Some widely used antidepressants such as imipramine, clomipramine, and citalopram have been found to possess antineoplastic effects. In the present study, these compounds were found to induce apoptotic cell death in human acute myeloid leukemia HL-60 cells. Apoptosis induced by the antidepressants was identified by electron microscopy and conventional agarose gel electrophoresis and was quantitated by propodium iodide staining and the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) via flow cytometry. Treatment with apoptosis-inducing concentrations of the antidepressants (80 microM imipramine, 35 microM clomipramine, or 220 microM citalopram) caused induction of caspase-3/caspase-3-like activity, which was monitored by the cleavage of poly(ADP-ribose) polymerase (PARP), the loss of the 32 kD caspase-3 (CPP32) precursor, and the cleavage of the fluorescent CPP32-like substrate PhiPhiLux. Pretreatment with a potent caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl-ketone (zVAD-fmk) inhibited antidepressant-induced CPP32/CPP32-like activity and apoptosis. Furthermore, activation of caspase induced by the antidepressants was preceded by the hypergeneration of intracellular reactive oxygen species (ROS). These results suggested that the antidepressants may induce apoptosis via a caspase-3-dependent pathway, and induction of apoptosis by the antidepressants may provide a clue for the mechanism of their antineoplastic effects.

Antidepressive Agents↗
PubMed1979

A sensitive method for the simultaneous determination in biological fluids of imipramine and desipramine or clomipramine and N-desmethylclomipramine by gas chromatography mass spectrometry.

A procedure is described which permits the simultaneous determination of imipramine and desipramine or clomipramine and N-desmethylclomipramine in serum or plasma for concentrations in the range of 1-200 ng ml-1. Detection limits of 0.2 ng ml-1 for imipramine and 0.1 ng ml-1 for desipramine were demonstrated with a signal-to-noise ratio maintained at 2:1 or better. The method relies on the derivatization of the secondary amines with heptafluorobutyric anhydride and is based on the combined use of gas chromatography, electron impact mass spectrometry and computerized data handling. The assaying procedure is specific, accurate and precise. It is suitable for routine analyses and has sufficient sensitivity to permit monitoring the drug and metabolite levels in human plasma or serum resulting from a single therapeutic dose.

Chromatography, Gas↗
PubMed2004

Decrease of the platelet 5-HT2A receptor function by long-term imipramine treatment in endogenous depression.

BACKGROUND: Animal studies have found that many antidepressants induce decreases in both the density and the functional activity of the serotonin 2A (5-HT2A) receptor subtype. However, the extrapolation of findings to humans has been inconclusive. A physiological platelet response mediated by this receptor, the serotonin-amplified platelet aggregation, was measured to study whether long-term antidepressant treatment induces changes in 5-HT2A receptor functioning in endogenous depressed patients. METHOD: The percentage of serotonin-amplified platelet aggregation to adenosine diphosphate (ADP) was studied in 15 untreated patients with major depressive disorder (DSM-IV) with endogenous features (Newcastle scale). This index was used as an indirect measurement of the functional status of platelet 5-HT2A receptors. Aggregation studies were repeated once remission of the symptoms was achieved during treatment with imipramine (150-300 mg/day). A group of 15 concurrent normal subjects was used as a control. RESULTS: A statistically significant decrease (p = 0.038) in the percentage of serotonin-amplified platelet aggregation to ADP was observed when remission was achieved (after 145 +/- 27 days). CONCLUSIONS: The results showed a decrease in a platelet functional response mediated by 5-HT2A receptors following effective imipramine treatment, suggesting that desensitization or down-regulation of the 5-HT2A receptor function could be linked to the therapeutic effect of some antidepressants. The data also support the use of platelet aggregometry as a surrogate measurement of antidepressant action, particularly in intra-subject designs.

Adult↗
PubMed1979

Comparisons of maprotiline with imipramine in severe depression: a multicenter controlled trial.

The efficacy and safety of maprotiline (Ludiomil) was compared to imipramine in patients with manic-depressive illness, depressed type (DSM II 296.2). Three hundred forty-one patients from 16 different centers entered this four-week double-blind controlled trial, with 171 in the maprotiline and 170 in the imipramine group. Efficacy measurements included the Hamilton Depression Scale, the Self-Rating Depression Scale, and the Investigator's Overall Assessment of Effectiveness. Tolerability was monitored by collection of treatment-emergent signs and symptoms (TESS), blood pressure and pulse measurements, EKGs, and EEGs. Dosage was fixed for the first week at 50 mg t.i.d. and thereafter could be varied between 50 and 300 mg daily. Clinically and statistically significant reductions in symptomatology were noted in both drug groups for most efficacy parameters at each visit during therapy. Comparison between the drug groups revealed no difference in terms of the scales utilized. A trend toward fewer TESS in the maprotiline group was noted, especially for the side effects nausea, nervousness, and increased sweating.

Adolescent↗
PubMed1976

Comparison of observed and predicted first-pass metabolism of imipramine in humans.

The first-pass metabolism of imipramine was calculated based on the dose, hepatic blood flow, and total area under the plasma-time curve after oral administration of 0.71 +/- 0.03 mg/kg of imipramine to four individuals suffering from mild depression. The predicted values of first-pass metabolism ranged from 37 to 68%, consistent with experimentally derived estimates.

Adult↗
PubMed1979

High-performance liquid chromatographic assay for imipramine, desipramine, and their 2-hydroxylated metabolites.

High-performance liquid chromatographic method is presented for the simultaneous determination of imipramine, desipramine, and their 2-hydroxylated metabolites in plasma. The method involves a simple plasma extraction at basic pH with organic solvent, chromatography on a silica gel column, and fluorescence detection. Correlation with a GLC-mass spectrometric method for imipramine and desipramine is illustrated. The method can detect 1 ng of each component/ml of plasma, sufficient sensitivity for pharmocokinetic studies.

Chromatography, Gas↗
PubMed1981

Metabolism of imipramine by microorganisms.

The microbial metabolism of imipramine was studied using selected fungal organisms. The major microbial metabolites were isolated, and their structures were established by spectroscopic analyses (particularly 13C-NMR) and by comparison with authentic samples. The microbial metabolites identified included 2-hydroxyimipramine, 10-hydroxyimipramine, iminodibenzyl, imipramine-N-oxide, and desipramine; these metabolites also have been found in mammalian metabolism studies.

Biotransformation↗
PubMed1983

Demethylation of imipramine by enteric bacteria.

The ability of a number of aerobic and anaerobic bacteria to N-demethylate imipramine (I) to desipramine (II) has been investigated. Of the bacteria investigated, almost half were known inhabitants of the human GI tract. More than half of the enteric bacteria studied were capable of N-demethylating imipramine (I) to desipramine (II) to some extent in at least one medium. It was found that the medium in which the organism was grown had a significant effect on the N-demethylase activity observed.

Bacteria, Aerobic↗
PubMed2002

Imipramine, mianserine and maprotiline block delayed rectifier potassium current in ventricular myocytes.

Imipramine, mianserine and maprotiline are three widely used antidepressant drugs with different chemical structure. In the present work we have studied the effects of these drugs on the delayed rectifier potassium current (I(K)) in myocytes isolated from rat ventricle. The delayed rectifier potassium current, responsible for action potential termination, is blocked by all of the three drugs I(K)studied in a state-independent manner. Imipramine and mianserine block I(K)in a 1 : 1 drug-receptor interaction, whereas maprotiline shows a negative cooperativity in the interaction between the channel complex and drug molecules.

Action Potentials↗
PubMed1976

Treatment of experimental imipramine and desipramine poisoning in the rat.

The influence of orally administered activated charcoal on organ concentrations of parenteral imipramine and desipramine was investigated. Ancillary distribution experiments indicated that the gastroenteral cycle of these substances might be more important than the enterohepatic cycle. Nevertheless the effectiveness of repeated activated charcoal dosage in lowering antidepressant concentrations of visceral organs is unpredictable. This is interpreted as a consequence of predominant binding of these drugs in the tissues, in contrast to drugs like acetosal and the barbiturates, which are distributed more evenly in the body water. The conclusion is, that activated charcoal has only limited value as an anitdotal adsorbent in imipramine or desipramine poisoning.

Adsorption↗
PubMed1975

Effect of ECT and imipramine treatment on the concentration of 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) in the cerebrospinal fluid of depressed patients.

The influence of probenecid administration on 5HIAA and HVA concentrations in the CSF of depressed patients, was studied before and after treatment with imipramine or ECT. The average increase of the two metabolites in the CSF after probenecid was similar in the untreated depressed patients and in the same patients improved after both imipramine or ECT treatment. The treatment determined a significant increase in the CSF concentration of the acid metabolites also before the probenecid administration.

Adult↗