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PubMed1981

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↗
PubMed1980

Uptake of 5-hydroxytryptamine and dopamine into platelets from depressed patients and normal subjects--influence of clomipramine, desmethylclomipramine and maprotiline.

Platelet uptake of 5-hydroxytryptamine (5-HT) and dopamine (DA) in normal subjects in vitro has already been shown to be significantly inhibited by clomipramine and less markedly by maprotiline (Turner and Ehsanullah, 1977). This effect has now been studied in greater detail, in patients categorized as having endogenous or neurotic/reactive depression, treated or untreated, and in normal volunteers, in whom the inhibitory activity of the metabolite desmethylclomipramine was also studied. Platelet uptake of 5-HT and DA in both types of depression is lower than in healthy, which supports the hypothesis that central monamine function is reduced or impaired in depressives. Clomipramine potently inhibits platelet uptake of DA as well as 5-HT, its antidepressant action cannot be attributed to 5-HT alone, while the observation that maprotiline has no effect on 5-HT uptake shows that its antidepressant action is not based on a serotonergic mechanism. Desmethylclomipramine has a marked inhibitory effect on platelet 5-HT uptake and its effect on DA uptake is greater than that of the parent compound.

Adjustment Disorders↗
PubMed1995

[Follow-up of Werlhof disease after onset of treatment with maprotiline].

Whereas leucocytopenia is reported to be a relatively frequent side-effect of treatment with tricyclic and tetracyclic antidepressants and atypical neuroleptic agents, isolated thrombocytopenias are rare. To our knowledge there are no reports of thrombocytopenia in connection with the tetracyclic antidepressant maprotiline. This report describes the case of a 53-year-old female patient with neurotic depression and an initially unsuspected chronic idiopathic thrombocytopenic purpura (ITP). Following previous treatment with an angiotensin-converting enzyme inhibitor, cilazapril, and an estrogen derivative, the patient developed an episode of the ITP after beginning treatment with maprotiline. The possible aetiology and the course of the illness are discussed.

Amitriptyline↗
PubMed1996

[Torsades de pointes in a patient under long-term maprotiline therapy. Apropos of a case].

The authors report the case of a patient who presented with wave burst arrhythmia related to long-term treatment with maprotiline. This case is interesting, as few cases of this type of complication have been reported in patients receiving long-term tetracyclic antidepressants, and the development of such a complication indicates the need for regular electrocardiographie surveillance of patients treated with heterocyclic antidepressants. Lastly, prolonged intensive care monitoring is required in the case of maprotiline-induced wave burst arrhythmia.

Aged↗
PubMed1992

Effects of zimeldine and its metabolites, clomipramine, imipramine and maprotiline in experimental allergic neuritis in Lewis rats.

The influence of the selective serotonin (5-HT) reuptake inhibiting antidepressant zimeldine and its metabolite norzimeldine was tested on experimental allergic neuritis (EAN) in Lewis rats, which is an animal model of the Guillain-Barré syndrome (GBS) in man. Zimeldine and norzimeldine both suppressed clinical signs of actively induced EAN when given at a dose of 20 mg/kg/day intraperitoneally via osmotic pumps. The effects of zimeldine, its metabolites norzimeldine and CPP 200 as well as of the antidepressants clomipramine, imipramine and maprotiline on in vitro immune response were tested. Thereby we used an immunospot assay for interferon-gamma (IFN-gamma) produced by lymph node mononuclear cells (MNC), which reflects number of memory T lymphocytes activated by antigen or lectin, in this experiment bovine peripheral nerve myelin (BPM) and phytohemagglutinin (PHA), respectively. In the IFN-gamma secretion assay zimeldine, CPP 200, clomipramine and maprotiline all in a concentration-dependent mode reduced the number of IFN-gamma secreting cells while norzimeldine and imipramine did not affect the IFN-gamma secretion. In assays for proliferation in response to antigen or lectin, the concentration 10(-4) M was judged toxic for all substances tested, and at concentrations below that all but zimeldine showed a dose-dependent slight reduction of MNC proliferation. The action of several drugs on induced T cell secretion of IFN-gamma suggests that the mechanisms for the suppressive effect of zimeldine and norzimeldine on EAN symptoms can be due to an action on myelin T cell autoreactivity. All the monoamine reuptake inhibiting antidepressants tested in this study showed immunomodulatory effects by either a reduction of the number of IFN-gamma-secreting cells or the MNC proliferation. These observations call for further studies of immunological mechanisms in the pathogenesis of mental disorders as well as on the potential role of drugs acting on the monoamine systems in the treatment of recognized autoimmune diseases.

Animals↗
PubMed1990

Alpha 2-adrenoceptor responsivity in depression: effect of chronic treatment with moclobemide, a selective MAO-A-inhibitor, versus maprotiline.

The effect of chronic treatment with the selective and reversible MAO-A-inhibitor moclobemide (MOC) vs. the norepinephrine reuptake inhibitor maprotiline (MAP) on alpha 2-adrenoceptor responsivity was studied by clonidine (CLON)-evoked growth hormone (GH) release in major depressive disorder. Compared to matched controls the depressed patients showed attenuated CLON-induced GH responses before treatment with MOC or MAP. Chronic treatment with both MOC and MAP significantly improved the depressive symptomatology. Although a trend toward increased GH responses to CLON was demonstrated after treatment in both groups, neither MOC nor MAP had a complete effect on restoration of alpha 2-adrenoceptor responsivity. No difference in insulin-like growth factor I (IGF-I) plasma concentrations before and after treatment with MOC or MAP was found. Our results support the view that antidepressants with different mechanisms of action may be capable of restoring alpha 2-adrenoceptor function during recovery from a major depressive episode.

Adult↗
PubMed1995

Chronic administration of the antidepressants phenelzine, desipramine, clomipramine, or maprotiline decreases binding to 5-hydroxytryptamine2A receptors without affecting benzodiazepine binding sites in rat brain.

1. The effects of chronic administration of five antidepressant drugs on the benzodiazepine and 5-HT2A binding sites in the same rat brain were assessed. 2. Clomipramine, desipramine, maprotiline, fluoxetine, and phenelzine (all 10 mg/kg/day) were administered s.c. for 21 days by Alzet osmotic minipumps. 3. Results showed that none of the drugs changed the density or affinity of benzodiazepine binding sites, yet at the same dose all the drugs with the exception of fluoxetine decreased binding to 5-HT2A receptors in the same animals.

Animals↗
PubMed1994

Acute vs. chronic EEG effects in maprotiline- and in clomipramine-treated depressive inpatients and the prediction of therapeutic outcome.

Patients treated with the norepinephrine uptake inhibitor maprotiline showed an opposite tendency between acute and chronic effect of EEG. Whereas the acute effect indicated a decrease upon EEG vigilance, the chronic effect indicated an increase. Under clomipramine which acts upon different transmitter systems in a complex, up to now not fully understood way, acute and chronic EEG effects could not be differentiated.

Adult↗
PubMed1992

Amitriptyline versus maprotiline in postherpetic neuralgia: a randomized, double-blind, crossover trial.

Amitriptyline (AT) relieves some patients with postherpetic neuralgia (PHN). Many patients suffer side effects and better therapies are necessary. The aim of this study was to evaluate the efficacy of maprotiline (MT) (noradrenergic) compared to AT (mixed noradrenergic and serotonergic) in this disorder. Thirty-five patients entered a randomized, double-blind, crossover trial of these two agents. We found that MT relieved PHN in many patients but was not as effective as AT. Side effects were troublesome with both agents. Relief of steady pain, brief pain and pain on tactile stimulation occurred. Four groups of responses were identified. Some patients reported relief with both agents, some with neither agent and others with only one of the drugs. Most patients were not depressed and analgesia was observed to occur without change in depression ratings in most patients who responded. This result provides evidence that in some patients AT may act via a selective noradrenergic mechanism in relieving PHN and that individuals may differ in the balance and type of neurotransmitters inhibiting pain. Selective noradrenergic agents may be effective if AT fails.

Aged↗
PubMed1984

Measurement of maprotiline and oxaprotiline in plasma by high-performance liquid chromatography of fluorescent derivatives.

The antidepressant maprotiline and its hydroxylated analogue oxaprotiline were assayed in plasma by solvent extraction and formation of fluorescent derivatives, which were purified by thin-layer chromatography and quantitated by high-performance liquid chromatography with fluorescence monitoring. The procedure possesses a high sensitivity, accuracy and reproducibility, and metabolites of the drugs did not interfere.

Anthracenes↗
PubMed1981

Quantitative high-performance liquid chromatographic assay for the determination of maprotiline and oxaprotiline in human plasma.

A procedure is described which permits the determination of maprotiline and oxaprotiline in human blood or plasma at therapeutic concentrations. The biological fluids are extracted with base and the extract is injected into a high-performance liquid chromatograph. The substances are detected by a UV detector operating at 214 nm, amitriptyline being used as internal standard. Concentrations as low as 2 ng per sample can be measured.

Anthracenes↗
PubMedDate not supplied

Determination of maprotiline and N-desmethylmaprotiline from biological fluids by HPLC.

A reversed-phase high-performance liquid chromatographic method has been developed for the simultaneous quantitation of maprotiline and its desmethylated metabolite from biological fluids. In this method, the samples were washed with hexane at acidic pH and then extracted with the same solvent at alkaline pH in the presence of an amine carrier. The drugs were eluted from the C18 column with acetonitrile (30%) in phosphate buffer (pH 2.5) and detected by their UV-absorbances at 205 nm. Peak identification was based on retention times and desmethyldoxepine was used as an internal standard for quantitation. Possible interferences were few; sensitivity (detection limit, 11 nmoles/L) and reproducibility (CV 2-2.5%) were good. Only about 10 minutes of chromatographic time was needed for one sample. Application for screening toxic drugs is suggested and briefly discussed.

Anthracenes↗
PubMedDate not supplied

Effective column extraction from decomposed tissue in a suspected overdose case involving maprotiline and amitriptyline.

This paper describes the use of a Celite 560 column extraction technique in the initial separation of drugs from the contents of the skull of a severely decomposed body. Analysis of the extract obtained resulted in the determination of the presence of amitriptyline, and maprotiline and two of its metabolites. As a consequence, the laboratory was able to provide the medical examiner with information concerning an extremely difficult case.

Amitriptyline↗
PubMed1983

Liquid chromatographic separation of antidepressant drugs: II. Amoxapine and maprotiline.

The simultaneous serum analysis of amoxapine (AMOX) and its major metabolite 8-hydroxyamoxapine (8-OH AMOX), and maprotiline (MAP) and its major metabolite desmethylmaprotiline (D-MAP) by high-performance liquid chromatography (HPLC) and ultraviolet detection is described here. AMOX and 8-OH AMOX were detected at 254 nm at 0.01 absorbance units full scale (AUFS). MAP and D-MAP were detected at 214 nm at 0.05 AUFS. Serum (1.0 ml collected in plastic) extraction was by Bond-Elut C18 columns. The compounds of interest were eluted from the columns with 10 mM methanolic ammonium acetate. The eluates are evaporated at 56-58 degrees C and reconstituted with 200 microliter of mobile phase. The mobile phase was absolute ethanol-acetonitrile-tert-butylamine (98:2:0.05, vol/vol), and the flow rate was 2.0 ml/min. Absolute recoveries range from 97 to 100% for all compounds. HPLC was done on a 5-micron (4.6 X 250 mm) silica-packing column (normal phase). Separations on a 10-micron silica column (3.9 X 300 mm) are also discussed. Peak height ratios using trimipramine as the internal standard were linear for each drug between 25 and 1080 ng/ml. AMOX and 8-OH AMOX ratios with promazine as the internal standard were linear between 25 and 1080 ng/ml. Detection limits were 3 ng/ml for AMOX and 8-OH AMOX, 12 ng/ml for D-MAP, and 15 ng/ml for MAP. Coefficients of within-day and day-to-day variation at three concentration levels were less than 10.8% and 10.5%, respectively, for all compounds. Correlations of AMOX, 8-OH AMOX, and MAP sample assays using gas chromatography (or gas chromatography-mass spectrometry) and this method were compared. Steady-state daily dosages and corresponding serum levels are presented for seven patients. AMOX and 8-OH AMOX concentrations for 37 patients are given; these show that the ratios of these compounds are highly variable between patients. MAP and D-MAP concentrations for 30 patients show that D-MAP can be a significant fraction of the circulating drug. Assay time for 8-OH AMOX/AMOX was 6.5 min and less than 13 min for D-MAP/MAP.(ABSTRACT TRUNCATED AT 250 WORDS)

Amoxapine↗
PubMed1982

Differences of sympathomimetic and anticholinergic action of OH-maprotiline and its R (-)-enantiomer.

1 C 49802 B-Ba and CGP 12103/A are the racemate and the R (-)-enantiomer respectively of the hydroxylated derivative of the tetracyclic antidepressant maprotiline, which differed in their ability to block noradrenaline-uptake and in their anticholinergic activity in animal models. 2 The sympathomimetic and anticholinergic activities of both substances were evaluated in eight healthy subjects and compared with the treatment with placebo and amitriptyline. 3 Heart rate, pupillary diameter, stimulated salivary flow rate and blood pressure were measured over a 15 h period keeping a very strict protocol. Plasma catecholamine levels were determined. 4 Saliva production was diminished following the administration of C 49802 B-Ba, CGP 12103/A and amitriptyline. 5 A moderate, but significant increase in heart rate and mean arterial blood pressure in the recumbent position was observed when C 49802 B-Ba was given. 6 The results in man are in agreement with the different activities found in animal experiments. 7 It can be concluded that the S (+)-enantiomer which the racemate contains is more active than the R (-)-enantiomer as to the anticholinergic and the sympathomimetic property.

Adult↗
PubMed1987

Serum levels of maprotiline and its adverse effects on depressed patients.

The relationships between the side effects of maprotiline (MPT) and the serum concentration of MPT and desmethylmaprotiline (DMPT) were investigated with 27 blood samplings in 15 depressed inpatients. There were significant correlations between the side effects and serum levels of MPT and DMPT. Mild side effects frequently occurred at levels of more than 130 ng/ml of MPT and 70 ng/ml of DMPT. At more than 220 ng/ml of the MPT levels and 110 ng/ml of DMPT levels, severe side effects occurred. Nearly sigmoidal serum level/side effect response curves occurred with both compounds.

Adult↗
PubMed1987

A comparison of maprotiline and its desmethylated metabolite serum concentrations in outpatients and inpatients.

An investigation was conducted on drug defaulting in 26 depressed patients (11 outpatients and 15 inpatients) treated with maprotiline (MPT), using the interrogation methods and measurements of drug serum levels. All the outpatients visited the clinic regularly and complied with taking the prescripted drugs as directed. The results were as follows: (1) The relationships between the MPT and desmethylmaprotiline (DMPT) serum levels and the daily MPT doses showed highly linear regressions in all the patients, and in the inpatients and outpatients separately. There were significant differences between the regression coefficients obtained in the outpatients and inpatients with respect to MPT (P less than 0.01) and DMPT (P less than 0.001). There was a discrepancy between the results from the patients' reports and measurements of the drug serum levels. This finding indicated noncompliance by the outpatients. (2) Comparing various factors of the outpatients to those of the inpatients, the DMPT/MPT ratio of the former was higher than that of the latter (P less than 0.05). This was also due to the patients' noncompliance, and this ratio, therefore, was considered to be a sensitive marker for checking the compliance of the patients treated with MPT.

Adult↗
PubMed1985

Cutaneous vasculitis from maprotiline.

An 83 year old woman with depression, while receiving maprotiline, developed a vasculitic skin eruption which resolved on discontinuing the drug. Vasculitis has not previously been reported with this drug.

Aged↗