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At least 19 recordsLinked to original sources

PubMed1979

The relative toxicity of amitriptyline, imipramine, maprotiline and mianserin in rabbits in vivo.

1. Conscious or barbiturate-anaesthetized rabbits were slowly infused intravenously with solutions of amitriptyline, imipramine, maprotiline or mianserin, usually until death occurred. 2. Amitriptyline produced death at the lowest dose, imipramine and maprotiline were intermediate while much higher doses of mianserin were required. 3. Convulsions were induced by the antidepressants in all conscious rabbits and the order of potency of the drugs in producing this effect was amitriptyline greater than or equal to imipramine greater than maprotiline greater than mianserin. 4. All four drugs produced a reduction in heart rate and blood pressure in the anaesthetized rabbits and the order of potency in this respect was amitriptyline greater than imipramine greater than maprotiline greater than mianserin. 5. All four drugs produced significant changes in the ECG compared with control rabbits. The P-R interval was lengthened (potency order amitriptyline greater than imipramine greater than or equal to maprotiline greater than mianserin) and the QRS complex was widened (potency order amitriptyline greater than imipramine greater than or equal to maprotiline greater than mianserin). 7. It is concluded that all four drugs show the toxic effects classically associated with tricyclic antidepressants but the relative toxicity amongst these agents varies considerably and is in the order amitriptyline greater than imipramine greater than maprotiline greater than mianserin.

Amitriptyline↗

PubMed1975

Pharmacological studies of drug action on CNS, with special reference to effects of maprotiline.

The effects of maprotiline, mainly on the CNS, were examined and compared with those of imipramine, methamphetamine and chlorpromazine. In the repeated administration and the stroboscope studies, maprotiline exhibited actions to increase behavioral activities of animals, just like amphetamine and imipramine. This appears to attest to pharmacological effects of maprotiline as an anti-depressant. It is noted, however, that whereas maprotiline shows a slight anti-apomorphine action in dogs and an inhibition of the spinal reflex action potential in cats, such actions are not recognized in other anti-depressants of the tricyclic groups including imipramine, amitriptyline, etc. These differences suggest the tranquilizing action of maprotiline at work, probably forming a specific pharmacological feature of maprotiline. Also, maprotiline increases body weight of rats strikingly, which seems to offer a wide range of clinical applications of this drug.

Action Potentials↗

PubMed1976

A double-blind comparison of lithium carbonate and maprotiline in the prophylaxis of the affective disorders.

A double-blind prospective study was carried out comparing the prophylactic effect of maprotiline and lithium carbonate over a period of one year in patients suffering from recurrent affective disorders. The average Affective Morbidity Index was lower, but not significantly so, in patients treated with lithium. A further analysis, based on dividing patients into those with no affective morbidity and those who showed some affective morbidity during the study, demonstrated lithium carbonate to be significantly superior to maprotiline both in the group as a whole and in unipolar depressives. A correlation between high plasma maprotiline concentration and low morbidity was observed and was in line with an earlier report. A highly significant negative correlation (r=-0-97; p less than 0-001) was found between plasma maprotiline concentration and body weight. Although the results showed lithium carbonate to be superior to maprotiline in the study, it should be emphasized that the plasma levels of lithium were constantly monitored and maintained at what is considered to be its optimum concentration, whereas the maprotiline treated patients were kept on a fixed dosage regime irrespective of plasma levels.

Adult↗

PubMed1977

Efficacy, side-effects, plasma and blood levels of maprotiline (Ludiomil).

Two trials of maprotiline (Ludiomil) were performed in general practice. In the first study depressed patients were given either 75 mg of maprotiline in a single dose or 25 mg three times daily. Assessments of the severity of depression and of side-effects were made initially and following 1, 2 and 4 weeks' treatment. At each assessment measurements of plasma levels of maprotiline were made. A second trial was performed in which some patients receiving 75 mg single dose of maprotiline had whole blood levels of maprotiline assayed. Steady-state levels of maprotiline were achieved after one week but these levels showed considerable individual variability. No clear correlation emerged between clinical response, side-effects and plasma or blood levels. Some of the factors which may be responsible are discussed.

Adult↗

PubMed1977

A comparative study of maprotiline (Ludiomil) and viloxazine in the management of depressed patients in general practice.

A double-blind, comparative, multicentre study comparing the efficacy and tolerability of maprotiline (Ludiomil) and viloxazine as antidepressants in general practice usage is described. Progress was measured at weekly intervals over the 4-week trial duration using a modified Hamilton Rating Scale and patient self-assessment visual analogue scales. A total of 127 patients were randomized into two groups; 63 patients being allocated maprotiline and 64 patients being allocated viloxazine. Of the patients receiving maprotiline, 12 withdrew during the course of the study compared to 9 patients receiving viloxazine. Maprotiline appeared to be superior to viloxazine on the sleep and sadness scales and some evidence to show it to be better also on the tension scale. Whilst the trend favoured maprotiline, the two drugs did not appear to be significantly different on either the doctors' or the patients' assessments. There was little to choose between the drugs in terms of side-effects or ultimate patient tolerability and preference.

Adjustment Disorders↗

PubMed1977

A comparison in rabbit isolated hearts of the dysrhythmogenic potential of amitriptyline, maprotiline and mianserin in relation to their ability to block noradrenaline uptake.

1. In isolated hearts of rabbits, perfusion with (-)-noradrenaline (0.0059 to 5.9 micronM) resulted in chronotropic and inotropic responses and a shortening of the interval between peak atrial and peak ventricular tensions (the A-V contraction interval). No dysrhythmias developed but at higher concentrations (590 micronM) 2 out of 7 hearts developed dysrhythmias (extrasystoles). 2. Perfusion with the antidepressants amitriptyline or maprotiline (4.8 micronM) or mianserin (28.8 micronM) reduced ventricular force, did not change heart rate and only amitriptyline reduced atrial force and lengthened the A-V contraction interval. At 4.8 micronM mianserin produced only a marginal shortening of the A-V contraction interval. 3. At these concentrations no dysrhythmias developed but at higher concentrations (amitriptyline 8 micronM, maprotiline 8 micronM, mianserin 60 micronM) all the agents produced dysrhythmias involving an interference with atrio-ventricular synchronization. 4. In the presence of mianserin (4.8 micronM) perfusion with noradrenaline (0.0059 to 5.9 micronM) shortened the A-V contraction interval and did not produce dysrhythmias. In the presence of amitriptyline or maprotiline (4.8 micronM) or mianserin (28.8 micronM) the A-V contraction interval generally lengthened and most hearts developed dysrhythmias (usually involving interference with atrio-ventricular synchronization). 5. [3H]-(-)-Noradrenaline uptake in perfused rabbit hearts and in mouse isolated atria or vasa deferentia was inhibited by the antidepressants to a similar extent, amitriptyline being marginally most potent (molar potency taken as 1.0), maprotiline being less potent (1.5) and mianserin least potent (2.0)). 6. It is concluded that of these three antidepressants, mianserin is least cardiotoxic in this preparation and that the ability of these antidepressants to predispose to noradrenaline-induced dysrhythmias is not related to blockade of noradrenaline uptake.

Amitriptyline↗

PubMed1978

Maprotiline and doxepin in the treatment of depression. A double-glind multicentre comparison.

Maprotiline (Ludiomil) and doxepin were compared in the treatment of depression in a double-blind multicentre trial. Four centres and 95 in- and out-patients took part in the trial. The severity of depression was evaluated with the aid of a visual analogue scale and nine target symptoms. Both maprotiline and doxepin diminished neurotic as well as psychotic depression significantly. The mean time of onset of action was 7.0 days in the maprotiline group and 7.7 days in the doxepin group. No statistically significant differences in antidepressive effect were found between the treatments. Two patients in the maprotiline group and four patients in the doxepin group discontinued the treatment because of unwanted effects, one patient in each group because of lack of efficacy and nine patients due to reasons not related to the treatment.

Adjustment Disorders↗

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↗

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↗

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↗

PubMed1976

[Clinical double-blind study with two different dosages of maprotiline (150 and 225 mg per day) (author's transl)].

Effects and side-effects of 150 mg and 225 mg maprotiline per day were compared by means of a double-blind trial in 20 depressed inpatients. The first 2 days patients received a high initial dosage of 300 mg per day. Patients were examined on days 0, 2, 5, 10, 15, 20, and 30. Symptoms were evaluated by the AMP system and the Hamilton scale for depressions. Laboratory examinations were carried out on days 0, 10, 20, and 30. Exanthemas developed in five patients, three of whom were on the higher dosage. Moreover, the lower dosage caused less fine hand tremor. Coinciding with the beginning of treatment a linear decrease of depressive symptoms was noted. This demonstrates the rapid onset of the antidepressant effect. Moreover, contrary to what has been stated for antidepressants generally, the onset of action was frequently noted well before 10-20 days of treatment. Some patients improved within a few days while others needed more time. The time lag until antidepressants influence depressive symptoms shows pronounced individual differences. No significant difference between the two dosages was found. The profiles show a better antidepressant effect for the higher dosage; however, because of a higher incidence of side-effects on the higher dosage of maprotiline, it cannot be recommended as routine. On the other hand, depressive inpatients should receive a daily dosage of at least 150 mg. Our findings suggest a dose-effect relationship for maprotiline.

Adult↗

PubMed1979

Effects of d-amphetamine, maprotiline, L-dopa, and haloperidol on the components of the predatory behavior of the ferret, Putorius furo L.

Ferret predation on rats was examined in an arena. One hour before the test one of the following drugs was administered. d-Amphetamine (0.8 and 1.4 mg/kg IM), MAPROTILINE (10 AND 40 Mg/kg orally), L-dopa (30 and 60 mg/kg orally), or haloperidol (0.14 and 0.6 mg/kg IM). Provided that capture was successful, the sequence of the behavioral components was not changed by these drugs. With the exceptions of paw movements and rolling over, which were not affected by the drugs, the components of predatory behavior were influenced differently. This leads to the assumption that a drug affects different mechanisms which control behavior. It is assumed that dopamine is involved in the control of capture elicitation as well as in the control of pursuit and biting. Capture elicitation was inhibited by d-amphetamine and L-dopa, but not by maprotiline, and was even facilitated by haloperidol. The orientation of pursuit movements and biting was impaired by L-dopa and improved by haloperidol, whereas maprotiline did not influence these components.

Animals↗

PubMed1975

Double-bind comparison of maprotiline with amitriptyline in the treatment of depressive illness.

Thirty patients closely matched for age, sex and duration of illness were treated with either amitriptyline or maprotiline in a double-blind, between-patient trial. Within limits of the small number of patients in the trial, maprotiline produced a significantly quicker improvement during the first 2 weeks as judged by the scores on the Hamilton Rating Scale. Maprotiline showed better tolerability than amitriptyline overall, especially as far as trial drop-out rates were concerned.

Adult↗

PubMed1976

Antidepressant treatment with maprotiline in the management of emotional disturbances in patients with acute myocardial infarction: a controlled study.

In coronary artery disease the patients usually manifest both anxiety and depression disturbances. A controlled clinical study was conducted to test the efficacy of a new antidepressant agent, maprotiline, in the early stages of acute myocardial infarction. The sample consisted of 126 patients, sixty-three receiving orally 25 mg of maprotiline twice daily and the remainder 5 mg of diazepam twice daily. Treatment lasted on an average two weeks (ten days to eight weeks). The depressive and/or anxiety conditions were rated on the basis of a questionnaire administered before and after treatment. Depression improved markedly in patients receiving maprotiline, while the two drugs developed a comparable anxiolytic action. Tolerability was good. No clinical or ECG evidence of cardiotoxic signs was detected. The importance of a drug with these characteristics in the management of emotional disturbances in the early stages of coronary artery disease is emphasized.

Acute Disease↗

PubMed1979

Neurobiochemical aspects of maprotiline (Ludiomil) action.

In the first part of the paper a short review of the neurobiochemical effects of the antidepressant drug maprotiline is given. Its most obvious effect is the inhibition of noradrenaline uptake in peripheral and central neurones. The peculiarity of this action consists in its high degree of selectivity, as no inhibition of serotonin uptake could be demonstrated in vivo. In the second part, the results of new experiments are described. These show that serotonin uptake is not diminished in rat mid-brain synaptosomes even after treatment with very high doses of maprotiline (600 mg/kg p.o.). In addition, the influence of the antidepressant on noradrenaline and serotnin uptake was studied in rat cerebral cortex, cerebellum, hypothalamus and pons-medulla. Dopamine and serotonin uptake were measured in the corpus striatum. Again, only the uptake of noradrenaline was found to be inhibited. There was not even a slight tendency towards inhibition of serotonin uptake. This high degree of selectivity distinguishes maprotiline from the tricyclic antidepressants and thus makes it an intersting 'extreme-type' uptake inhibitor.

Animals↗

PubMed1975

A controlled trial of maprotiline (Ludiomil) in depressed outpatients.

A double blind comparison is reported of a new tetracyclic antidepressant, maprotiline, with amitriptyline and placebo in psychiatric outpatients. Amitriptyline was significantly more effective than placebo in its global effect on depression. Maprotiline emerged as neither inferior to amitriptyline nor superior to placebo. Methodological difficulties prevented an adequate assessment of the anxiolytic activity of maprotiline.

Adult↗