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PubMed1984

Effects of self poisoning with maprotiline.

Self poisoning with maprotiline was studied in 41 patients (43 episodes) consecutively admitted to an intensive care unit. Thirty five patients had taken more than one drug or alcohol. Fifteen patients were in coma grade III or IV; 17 patients were still not conscious after 24 hours in the intensive care unit. Among six patients given ventilation the mean duration of ventilation in the five who recovered was 36 hours. Three patients had a cardiorespiratory arrest, and one patient died. Twenty eight patients had a QRS interval of 100 ms or more, and 15 patients had seizures. In six patients seizures were precipitated by physostigmine. Cardiotoxicity after overdosage of maprotiline is equal to if not greater than that found after overdosage of conventional tricyclic antidepressants. Overdosage of maprotiline is more often associated with seizures than overdosage with tricyclic antidepressants. Physostigmine further increases the risk of seizures and should not be used in cases of overdosage of maprotiline.

Adult↗
PubMed1982

Nomifensine and maprotiline in endogenous depression: comparative efficacy and side effects.

50 patients suffering from endogenous depression were admitted to a double-blind study comparing the efficacy of nomifensine and maprotiline and the side effects associated with treatment. A total of 28 patients, 14 on nomifensine and 14 on maprotiline completed the study. Therapeutic efficacy was evaluated by means of the Hamilton Rating Scale for Depression before administering the drugs and on days 7, 14, 21 and 28. Also noted if present was the day on which marked improvement was reported. At each assessment period incidence and severity of side effects were registered. On the basis of this study, nomifensine and maprotiline were both found clinically to have marked antidepressant action. The difference in response did not reach statistical significance, although there was a trend towards better improvement on nomifensine at the end of the 1st and 4th weeks. There was a rapid onset of action with both compounds. Significantly more severe side effects developed in those patients treated with maprotiline compared to those treated with nomifensine.

Adolescent↗
PubMed1994

Effectiveness and tolerance of the hypericum extract LI 160 compared to maprotiline: a multicenter double-blind study.

A randomized, double-blind study examining the effectiveness and tolerance of a standardized hypericum preparation when compared to maprotiline was performed in a group of 102 patients with depression, in accordance with ICD-10, F 32.1. The study was conducted in the offices of neurology and psychiatry specialists. The patients received, over a period of 4 weeks, either 3 x 300 mg of the hypericum extract or 3 x 25 mg maprotiline pills of identical appearance. Effectiveness was determined using the Hamilton Depression Scale (HAMD), the Depression Scale according to von Zerssen (D-S), and the Clinical Global Impression Scale (CGI). The total score of the HAMD scale dropped during the 4 weeks of therapy in both treatment groups by about 50%. The mean values of the D-S scale and the CGI scale showed similar results, and after 4 weeks of therapy, no significant differences in either treatment group were noticed. The onset of the effects occurred up to the second week of treatment, but were observed earlier with maprotiline than with the hypericum extract. On the other hand, maprotiline treatment resulted in more cases of tiredness, mouth dryness, and heart complaints.

Adult↗
PubMed1979

Cross-over trial comparing the antidepressant effects of amineptine and maprotiline.

A double-blind controlled, cross-over trial was carried out in 70 depressed patients to compare the effectiveness and tolerability of amineptine with that of maprotiline. Patients were allocated at random to receive treatment with either 150 mg amineptine or 75 mg maprotiline daily for 6 weeks before being treated for a further 6 weeks with the alternative drug. Comparison of the response to treatment at the end of each period showed that amineptine was significantly better than maprotiline, and this was particularly marked in the 46 patients with exogenous depression where an effect was usually evident within 3 to 5 days. Only 6 patients in this group failed to show a response to amineptine compared with 19 to maprotiline. Both drugs appeared to be equally effective overall in patients with endogenous depression, although when amineptine was given as the second treatment there was an improvement in retardation. Few side-effects were reported during either treatment period.

Adult↗
PubMed1985

Effect of maprotiline on pentagastrin-stimulated acid secretion in man.

We have studied the effect of maprotiline, an antidepressant with a strong pronoradrenergic effect, on human gastric secretion. Twelve subjects (nine men and three women) entered the study; six had an active duodenal ulcer, and six were healthy volunteers. Each patient underwent two experiments with an interval of at least 48 h. In a randomized double-blind order, each patient received maprotiline or placebo intravenously during intravenous stimulation with pentagastrin (2 micrograms/kg/h). Thirty minutes after basal collection, pentagastrin was administered for 180 min by constant intravenous infusion. After 60 min placebo or maprotiline (1 mg/kg/h) was added to the intravenous infusion from the 60th to 120th min; thereafter 2 mg/kg/h were infused until the 180th min. Maprotiline infusion (2 mg/kg/h) inhibited significantly stimulated acid secretion in comparison with placebo in duodenal ulcer patients but not in healthy volunteers.

Adult↗
PubMed1976

Comparison of the effects of maprotiline (ludiomil) and clomipramine (anafranil) on serotonin uptake and tryptophan-binding in plasma.

The influence of maprotiline or clomipramine on plasma tryptophan-binding and brain tryptophan was studied in rats. Neither compound altered tryptophan-binding nor brain tryptophan levels after acute of chronic treatment. In a comparative study maprotiline and clomipramine were administered to healthy volunteers for 4 days and the concentrations of total and free tryptophan in plasma were determined. Serotonin uptake was also measured in the platelets from these subjects. Maprotiline treatment did not inhibit serotonin uptake nor did it have any influence on plasma tryptophan binding. Clomipramine also had no influence on plasma tryptophan-binding but strongly inhibited serotonin uptake into platelets. These results confirm the earlier observation that maprotiline has no influence on serotonin uptake and can be clearly distinguished from clomipramine.

Animals↗
PubMed1989

Effect of maprotiline combined with conventional neuroleptics against negative symptoms of chronic schizophrenia.

The therapeutic efficacy and target symptoms of maprotiline were tested by administering it in addition to conventional neuroleptic treatment for 10 weeks to a total of 32 chronic schizophrenic patients who showed no, or only partial, response to the neuroleptic medication. The final global improvement rating was 68.8% for all patients. Average therapeutic doses administered were 150 mg per day. Changes in psychotic symptoms were assessed by the Brief Psychiatric Rating Scale (BPRS), Psychiatric Evaluating scale (PES), and the Scale for the Assessment of Negative Symptoms (SANS). All mean improvement rates of these rating scales were observed at the 2nd week after the start of treatment, and maprotiline produced a marked amelioration in negative symptoms such as decreased spontaneity, blunted affect, emotional withdrawal, impaired work or recreation, etc. The incidence of side-effects was 37.5%. Constipation was the most frequently occurring side-effect. Neither side-effects nor laboratory test results were serious enough to discontinue the trial, except in the case of one chronic patient who showed acute exacerbation of symptoms due to maprotiline-induced insomnia, elation and hallucination. These results suggest that maprotiline improves the negative symptoms of schizophrenia by a noradrenaline potentiating action not demonstrated by dopaminergic or serotonergic reward systems.

Adult↗
PubMedDate not supplied

[Effects of 3 doses of maprotiline (25, 50 and 75 mg) on alertness and memory in healthy volunteers].

The effects on psychomotor and mnesic performance of acute oral doses of maprotiline (25, 50 and 75 mg) were evaluated in twelve healthy men in a placebo-controlled double blind study. A battery of tests was performed comprising: objective measures (critical flicker frequency, choice reaction time, memory tasks) and self rating evaluation (visual analogue scales). Tests session took place 15 hours after each treatment. Plasma concentrations of maprotiline were determined. Compared with placebo, maprotiline induced psychomotor impairment on both objective and subjective assessment in a dose related manner. No significant difference between maprotiline and placebo on memory test could be evidenced.

Adult↗
PubMed1989

Safety of maprotiline in treatment of cardiac patients with left anterior hemiblock.

Based on the reports that maprotiline has a relatively low cardiotoxicity, two depressed patients who had conduction abnormalities of the heart were treated with this medication. In both patients the conduction abnormalities were not affected adversely by maprotiline 100 to 150 mg daily for six weeks. In one patient premature ventricular beats disappeared after maprotiline treatment. In modest dosages, maprotiline seems relatively safe in depressed cardiac patients.

Anthracenes↗
PubMed1979

Epileptic phenomena induced in the cat by the antidepressants maprotiline, imipramine, clomipramine, and amitriptyline.

The epileptogenic properties of four tricyclic antidepressant drugs: maprotiline, imipramine, clomipramine, amitriptyline, were investigated in locally anesthetized cats immobilized with gallamine and supplied with neocortical, hippocampal, and reticular recording electrodes. The drugs were infused intravenously at a constant rate (0.5 or, in some cases, 0.25 mg/kg per min) up to a final dose of 45 mg/kg. Already in small doses (1 to 5 mg/kg) all four antidepressants produced local signs of epileptiform pathology. Generalized sustained discharges occurred, on the average, at between 20 and 25 mg/kg with all four drugs. Imipramine and amitriptyline, after the first or first few generalized discharges, led to a pattern of repeated short generalized seizures alternating with silent periods. Maprotiline invariably produced this later alternating pattern only after a 10- to 30-min period of a seminormal high amplitude pattern. Clomipramine assumed a position between maprotiline on the one hand and imipramine and amitriptyline on the other. Starting at doses of 2-4 mg/kg, imipramine, clomipramine and amitriptyline, all three being norepinephrine and serotonin uptake inhibitors, induced a high amplitude "sleep" pattern. Maprotiline, a norepinephrine uptake inhibitor, which is thought devoid of serotonin-uptake inhibiting properties, led to high amplitude slow waves only with doses of at least 12.5 to 15 mg/kg.

Amitriptyline↗
PubMedDate not supplied

Experimental evaluation of the antidepressant and neuroleptic activity of maprotiline.

Maprotiline, a tetracyclic antidepressant drug, was evaluated for antidepressant and neuroleptic activity. In antidepressant tests, maprotiline antagonized reserpine-induced ptosis in rats but, unlike the tricyclic antidepressants, was found to antagonize methamphetamine stereotypy in rats, to decrease the intensity of L-dopa induced behavioural syndrome in pargyline-pretreated mice and to be ineffective in intensifying the 5-HTP induced behavioural syndrome. In neuroleptic tests, maprotiline was found to, antagonize apomorphine-induced cage climbing behaviour, induce catalepsy, inhibit the CAR and traction response, decrease the spontaneous motor activity and exploratory behaviour, and to potentiate the hypnotic effect of pentobarbitone. Our results indicate that maprotiline exhibits a profile of activity which resembles the neuroleptics and most probably exerts post-synaptic striatal DA receptor blocking activity.

Animals↗
PubMed1984

Comparative cardiac effects of maprotiline and doxepin in elderly depressed patients.

In a double-blind study, 49 elderly patients with primary major depression, with or without cardiovascular disease, were treated with maprotiline or doxepin. Holter monitors, 12-lead ECGs, and orthostatic blood pressure measurements were used. Maprotiline was associated with decreased PVCs in patients with a "high" baseline rate, while doxepin was associated with increased PVCs in this group. There were no significant differences in orthostatic blood pressure changes between treatment and nontreatment phases or between the two drugs. Small but significant increases in heart rate and prolonged PR interval were noted with both drugs. QRS interval was prolonged by maprotiline but decreased by doxepin. Neither drug produced untoward effects in patients with stable angina or an old myocardial infarction. Maprotiline may have an antiarrhythmic effect which could be beneficial in the treatment of depression with concomitant PVCs. Conversely, doxepin may be more appropriate for depressed patients with heart block or intracardiac conduction delays. Further research is necessary to confirm these suggestions.

Aged↗
PubMed1983

Therapeutic superiority of maprotiline versus doxepin in geriatric depression.

In a double-blind study, 49 geriatric patients suffering from primary major depression were treated with maprotiline or doxepin. Efficacy and safety were assessed by the Hamilton Depression Rating Scale and the Zung Self-Rating Depression and Anxiety scales, side effects profile, routine laboratory tests, and measurements of blood levels. Although marked improvement was obtained with both antidepressants, patients on maprotiline showed statistically greater improvement than those on doxepin. No significant differences were detected between the two drugs with respect to side effects. A significant positive correlation was obtained between dosage and blood levels of maprotiline and doxepin, but there was no correlation between blood levels and clinical response. Overall, results suggest that maprotiline may be superior to doxepin in the treatment of geriatric depression.

Anthracenes↗
PubMed1981

Relative speed of onset of the antidepressant effect of maprotiline.

In a double-blind clinical trial conducted in general practice, maprotiline was compared with amitriptyline. Thirty-three of 40 patients completed the trial, 19 on maprotiline and 14 on amitriptyline. The Hamilton Depression Rating Scale was administered on days, 0, 7, 14, and 21, and a global rating scale of improvement was administered on day 21. Although there were significant reductions in the Hamilton scores by day 21 in both groups, with no significant difference between the compounds, maprotiline produced significantly greater improvement by day 7 than did amitriptyline. A review of published double-blind clinical amitriptyline or imipramine for treatment of depression supports our finding that maprotiline has a faster onset of action than the standard tricyclic antidepressants.

Amitriptyline↗
PubMed1977

Estimation of maprotiline in serum by gas-chromatography, with use of a nitrogen-specific detector.

We describe a gas-chromatographic procedure for estimating therapeutic concentrations of maprotiline, a new tetracyclic antidepressant, in serum by use of a nitrogen-specific detector. Desmethyldoxepin, a secondary amine similar in structure to maprotiline, is added as a mass internal standard to the specimen before extraction, to obviate the need for accurate measurements of volumes during extraction and analysis. Both maprotiline and the internal standard are converted to acetyl derivatives, to avoid the adsorption of secondary amines on the column. A highly selective liquid phase is used, which allows a very good separation of desmethyldoxepin, maprotiline, desmethylmaprotiline, and the interferences from serum and reagents.

Anthracenes↗
PubMed1979

Selected ion monitoring assay for the antidepressant maprotiline.

A procedure is described which permits the determination of maprotiline in biological fluids at concentrations ranging from 0.5 to 150 ng ml-1. It relies on the use of N-desmethylclomipramine or isotope labeled maprotiline as the internal standard, on derivatization of the secondary amines with heptafluorobutyric anhydride, and on the combined use of gas chromatography with chemical ionization 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 human blood levels expected from a single therapeutic dose for a week or longer. The method, which can monitor simultaneously isotope labeled and unlabeled maprotiline, can be used to great advantage for reducing variability problems encountered in bioavailability studies.

Anthracenes↗
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↗
PubMed1994

Frequency-dependent effects of amitriptyline and maprotiline on conduction in the guinea pig His-Purkinje-system in vivo.

In the Cardiac Arrhythmia Suppression Trial antiarrhythmic drug therapy with slow kinetic sodium channel blockers (class Ic antiarrhythmic drugs) was associated with excess mortality, presumably due to drug induced proarrhythmia. It has been suggested that the degree of rate-dependent conduction slowing produced by agents that have sodium channel blocking properties may be related to the proarrhythmic propensity of these agents. In the present study, rate-dependent conduction slowing by the antidepressants amitriptyline and maprotiline was investigated in anesthetized guinea pigs. After electrical ablation of the sinus node the left atrium was stimulated at cycle lengths between 200 ms and 500 ms. His bundle electrograms were registered by means of an epicardial electrode. Drugs were administered by i.v. infusion of 0.2 mg kg-1 min-1 for 30 min followed by 0.1 mg kg-1 min-1 for up to 30 min. Both drugs produced substantial rate-dependent conduction slowing within the His-Purkinje-system. The relationship between pacing rate and conduction slowing was well fitted by linear regression. The steepness of the regression line was significantly greater for amitriptyline than for maprotiline (slope factors: 9.10 x 10(-4) +/- 7.85 x 10(-5), n = 6, vs. 6.29 x 10(-4) +/- 2.97 x 10(-5), n = 6, P < 0.001), indicating that conduction slowing by amitriptyline exhibits a greater degree of rate-dependence than conduction slowing by maprotiline.(ABSTRACT TRUNCATED AT 250 WORDS)

Amitriptyline↗