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PubMed1986

Plasma tryptophan and tyrosine ratios to competing amino acids in relation to antidepressant response to citalopram and maprotiline. A preliminary study.

Pretreatment plasma ratios of tryptophan (Trp) and tyrosine (Tyr) to other large neutral amino acids were determined in 27 depressed patients who completed a double-blind trial of citalopram, a selective serotonin uptake inhibitor, against maprotiline, a selective noradrenaline uptake inhibitor. The Trp ratio and the Tyr ratio were decreased in the total patient sample as compared with healthy controls. Plasma Tyr ratio was normal in the endogenous, but significantly decreased in the non-endogenous depressives. There was no significant relationship between the plasma Trp ratio and the probenecid-induced accumulation of 5-HIAA in the CSF, or between the plasma Tyr ratio and HVA level in CSF, whereas the CSF level of MHPG correlated significantly with the plasma Tyr ratio. There was a significantly positive correlation between the Trp ratio, the Tyr ratio, their sum and the final Hamilton depression score in 14 patients treated with citalopram; on the whole, this association was evident also in the endogenous and non-endogenous subgroups. In 13 patients on maprotiline there was a significantly positive correlation between the plasma Tyr ratio and the percent reduction of Hamilton depression score; this association was poor in the endogenous, whereas a trend towards a correlation remained in the non-endogenous subgroup. The results suggest that the plasma Trp and Tyr ratios may be determinants of clinical improvement in depressed patients to treatment with citalopram and maprotiline. However, further studies are needed on larger patient samples to allow a firm conclusion.

Adult↗
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↗
PubMed1981

Toward a biochemical classification of depressive disorders. III: Pretreatment urinary MHPG levels as predictors of response to treatment with maprotiline.

Pretreatment urinary MHPG levels were examined in 28 depressed patients as a possible predictor of response to treatment with maprotiline, a tetracyclic antidepressant that exerts potent effects on norepinephrine uptake, but has little effect on serotonin uptake. Maprotiline was administered in doses up to 150 mg/day during the first 2 weeks after which time the dose could be increased incrementally up to 300 mg/day if indicated clinically. At 2 weeks, patients with low pretreatment urinary MHPG levels responded more favorably to treatment than did patients with high MHPG levels. At 4 weeks, patients with low MHPG levels continued to show more favorable responses; however, differences between the two groups were less clear-cut than at 2 weeks. The findings suggest the patients with low pretreatment urinary MHPG levels are more sensitive to, and respond more rapidly to, treatment with maprotiline than patients with high pretreatment urinary MHPG levels.

Anthracenes↗
PubMed2005

Changes in AMPA subunit expression in the mouse brain after chronic treatment with the antidepressant maprotiline: a link between noradrenergic and glutamatergic function?

Potentiation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor function has been proposed as being useful in the treatment of depression, but thus far, little is known about the possible changes in AMPA receptor expression in the brain, after antidepressant treatment. The present study was carried out to study the expression of AMPA receptor subunits in different brain regions of mice that had been chronically injected with maprotiline. The latter is a modified tricyclic antidepressant that functions as a noradrenaline uptake inhibitor. Daily intraperitoneal injection with 10 mg/kg maprotiline for 30 days resulted in significantly increased GluR1 and GluR2/3 subunit expression in the nucleus accumbens and dorsal striatum as detected by immunohistochemistry; and significantly increased GluR1 and GluR2/3 expression in the hippocampus, as demonstrated by Western blot analysis. No change, or a decrease in GluR2 expression was detected in all the brain regions by both immunohistochemistry and Western blots. The increase in GluR1 and GluR2/3, but no increase in GluR2 subunits suggests that there could be an increase in calcium permeability of AMPA receptors in limbic/striatal brain regions after maprotiline treatment. This could lead to increased synaptic activity or plasticity in the hippocampus and striatum, and may underlie the therapeutic effect of maprotline, and possibly, other antidepressant drugs.

Animals↗
PubMed2000

Technetium-99m DTPA inhalation scintigraphy in patients treated with fluoxetine and maprotiline: preliminary results.

Drug-metabolising enzymatic activities have been detected in tracheobronchiolar, bronchiolar and alveolar regions in the lungs. Induction of phospholipidosis by amine drugs such as clorphentermine has also been shown. This study aimed to investigate the effect of fluoxetine and maprotiline, which contain amine groups in their structure, on pulmonary epithelial membrane permeability. Twenty-seven patients (mean age 36+/-12 years) with various psychiatric problems, of whom 17 were treated with fluoxetine and 10 with maprotiline, were included in this study. Technetium-99m diethylene triamine penta-acetic acid (DTPA) aerosol inhalation scintigraphy was performed before and after 4-6 weeks of therapy. Following the inhalation of 1480 MBq 99mTc-DTPA for 3 min, lung images in a 64x64 matrix were obtained every minute for 30 min. Regions of interest were drawn around the periphery of the lungs and on the major airways. Clearance half-times (T 1/2) were calculated by placing a mono-exponential fit on the curves. Penetration index (PI) was calculated on the first-minute image. There was no difference between the clearance rates of 99mTc-DTPA before and after therapy for either the fluoxetine or the maprotiline group. After therapy, a significant decrease in PI was found in patients treated with fluoxetine (PI values before and after therapy: 0.53+/-0.03 and 0.49+/-0.05 respectively, P< or =0.05). This finding might have been due to the induction of increased synaptic serotonin (5-HT) by fluoxetine, which acts by inhibiting the re-uptake of 5-HT on presynaptic membranes. Bronchoconstriction of small and medium airways may be caused by direct and indirect effects of 5-HT on smooth muscle contraction.

Administration, Inhalation↗
PubMed1996

Effects of desipramine and maprotiline on the coeruleus-cortical noradrenergic system in anaesthetized rats.

Desipramine (1-3000 micrograms/kg i.v.) and maprotiline (1-10,000 micrograms/kg i.v.), two selective noradrenaline uptake blockers, inhibited the firing rate of noradrenergic locus coeruleus neurons and induced excitation of the prefronto-cortical neurons. The selective destruction of ascending noradrenergic pathways by intracerebroventricular injection of 6-hydroxydopamine antagonized the excitatory effect of desipramine and maprotiline on the prefronto-cortical neurons. These results suggest that desipramine and maprotiline dose dependently stimulate the electrical activity of prefronto-cortical neurons, probably by acting on noradrenergic cells of the locus coeruleus.

Animals↗
PubMed1983

Maprotiline in affective illness. Plasma concentration and clinical response.

Twenty patients suffering from endogenous depression were treated with maprotiline for 4 weeks. Blood samples were collected at weekly intervals and severity of depression assessed using the Hamilton Depression Rating Scale. No simple relationship between plasma maprotiline concentration and amelioration score was observed at week 3 (rs = 0.25) or week 4 (rs = -0.05). No significant difference in plasma concentrations between responders and non-responders was observed at week 4. Maprotiline was effective as an antidepressant in some patients.

Adolescent↗
PubMed1995

The serotonin reuptake inhibitor paroxetin is superior to the noradrenaline reuptake inhibitor maprotiline in the treatment of premenstrual syndrome.

Recent studies indicate that antidepressant drugs with potent serotonin reuptake inhibiting properties are effective in reducing the symptoms of premenstrual syndrome (PMS). In order to elucidate whether all antidepressant drugs are equally effective in the treatment of PMS or whether potent serotonin reuptake inhibition is a prerequisite for reducing premenstrual complaints, women suffering from severe PMS were treated daily for three menstrual cycles with a selective serotonin reuptake inhibitor, paroxetine (n = 22), or with a selective noradrenaline reuptake inhibitor, maprotiline (n = 21); in addition, a placebo group was included (n = 22). Six symptoms (irritability, depressed mood, tension/anxiety, increased appetite/craving for carbohydrates, bloating, and breast tenderness) were rated by the participants daily throughout the study. With respect to all outcome measurements, the symptom reduction obtained with paroxetine was significantly superior to that obtained with placebo; with respect to irritability, increased appetite/carbohydrate craving, bloating, and breast tenderness, as well as global self-rating, paroxetine was significantly superior also to maprotiline. The clear-cut superiority of paroxetine over maprotiline indicates that not all antidepressant drugs are equally effective in the treatment of PMS; rather, like panic disorder and obsessive compulsive disorder, but in contrast to depression, PMS apparently responds better to serotonin reuptake inhibitors than to antidepressants with a noradrenergic profile.

Double-Blind Method↗
PubMed2005

Are the effects of the antidepressants amitriptyline, maprotiline, and fluoxetine on inhibitory avoidance state-dependent?

State-dependent learning (SDL) is a phenomenon in which the retrieval of newly acquired information is possible if the subject is in the same physiological state as during the encoding phase. SDL makes it possible to separate the effects of drugs per se on learning from the effects due to changes in drug state during the task. The present work was designed to investigate whether the antidepressants amitriptyline (30 mg/kg), maprotiline (25 mg/kg), and fluoxetine (15 mg/kg) produce SDL of the inhibitory avoidance conditioning in male and female CD1 mice. In three separate experiments, independent groups were used for each pharmacological treatment and for each sex using a 2 x 2 experimental design. The results do not show SDL in any of the drugs. In the case of amitriptilyline, the data can be attributed to a memorization deficit, while the maprotiline results are interpreted as simultaneously influenced by memorization deficit and performance facilitation due to motor impairment. Fluoxetine treatment did not produce any deteriorating effect on the conditioning. Drugs had some different effects on the performance of males and females, males showing a slightly higher deterioration than females with administration of amitriptyline and maprotiline. This study shows that these antidepressants affect the acquisition/consolidation but not the retrieval process in the inhibitory avoidance learning.

Amitriptyline↗
PubMed1986

[Heart conduction disorders in acute maprotiline poisoning].

A case is reported of self-poisoning with maprotiline followed by prolonged disorders of intraventricular conduction. The cardiotoxicity of tetracyclic antidepressants was well established, but few cases were reported. Maprotiline pharmacokinetics explained the duration of the cardiovascular side-effects. The severity of maprotiline overdoses should not be underestimated.

Adult↗
PubMed2000

Visual perseveration: a new side effect of maprotiline.

OBJECTIVE: The aim of this paper is to describe a case of visual perseveration including palinopsia during maprotiline therapy. METHOD: A single case report. RESULTS: The patient, a 56-year-old depressive man, suffered from visual perseveration during maprotiline therapy. The visual perseveration was dose-related and disappeared with reduction and cessation of the therapy. CONCLUSION: The present findings suggest that maprotiline can induce visual perseveration including palinopsia in some patients.

Antidepressive Agents, Second-Generation↗
PubMed1982

Mianserin and maprotiline as compared to amitriptyline in severe endogenous depression. A new methodological approach to the clinical evaluation of the efficacy of antidepressants.

Present methodological problems in assessing the clinical efficacy of putative antidepressants require testing of various new strategies. The approach presented by the authors allows "natural" clinical treatments to be evaluated scientifically; double-blind conditions are replaced by other measures of bias control. In this paper, the clinical effectiveness of mianserin in homogenous groups of inpatients with severe endogenous depression is compared with that of maprotiline and amitriptyline. The frequency of change of the respective antidepressant by the physicians in charge as well as patients' self-evaluations based on v. Zerssen's Mood Scale served as outcome criteria. No difference in efficacy was found between maprotiline and amitriptyline, whereas mianserin was significantly less effective. The number of patients complaining of side effects from the two tetracyclic compounds was no less than in the case of amitriptyline. There were, however, qualitative differences; with maprotiline, myoclonic jerks were observed in some cases. The hypothesis that mianserin may possess sedative-anxiolytic rather than antidepressive properties is discussed in conjunction with methodological and theoretical implications.

Adult↗
PubMed1985

A fatal maprotiline intoxication.

A fatal maprotiline intoxication is presented. The postmortem anatomical and toxicologic findings are discussed, as is the mechanism of maprotiline toxicity. This report is, to the best of our knowledge, the sixth fatal maprotiline poisoning in the medical literature.

Adult↗
PubMed1980

Antidepressant drugs in anergic schizophrenia. A double-blind cross-over study with maprotiline and placebo.

Seventeen out of 20 inactive and emotionally withdrawn schizophrenic patients under long-term neuroleptic treatment completed a double-blind cross-over investigation of the possible activating effect of maprotiline, a relatively specific noradrenaline-reuptake inhibitor, compared with that of placebo. Each treatment phase lasted 8 weeks. No significant differences with respect to either the level of activity or schizophrenic symptoms were found between maprotiline (mean dose 138 mg/day) and placebo. Maprotiline provoked a slight psychotic exacerbation in one patient and sedation in another, four patients developed orthostatic hypotension, and two patients had an epileptic seizure. In the light of this and other studies, it must be concluded that antidepressant drugs do not represent any therapeutic advance in the treatment of inactive schizophrenic patients receiving neuroleptics.

Adult↗
PubMed1981

The antidepressant efficacy of zimelidine and maprotiline.

In a double-blind group comparison study of 39 patients with primary depressive illness zimelidine in a dose of 200 mg at night demonstrated the same order of antidepressant efficacy as maprotiline in a dose of 150 mg at night after either two or four weeks treatment measured by the amelioration or final score on the Hamilton Rating Scale (HRS) and on the Montgomery & Asberg Depression Rating Scale (MADRS). Both zimelidine and maprotiline demonstrated significant antidepressant activity at 2 weeks compared with 2 weeks prior treatment with placebo measured by amelioration on HRS (paired t 4.1 P less than 0.001, t 2.7 P less than 0.02) or MADRS (paired t 3.5 P less than 0.005, t 5.1 P less than 0.001). An item analysis of the MADRS showed significantly better sleep and appetite in the maprotiline-treated group compared with the zimelidine-treated group which is in accord with the pharmacology of the two compounds.

Adult↗
PubMed1987

Biochemical and pharmacological tests for the prediction of ability of monoamine uptake blockers to inhibit the uptake of noradrenaline in-vivo: the effects of desipramine, maprotiline, femoxetine and citalopram.

The ability of desipramine and maprotiline (NA uptake inhibitors), as well as citalopram and femoxetine (5-HT uptake inhibitors) to protect mice against brain NA depletion induced by H 77/77 (4-alpha-dimethyl-m-tyramine), has been compared with their ability to counteract reserpine (2.5 mg kg-1)- or apomorphine (16 mg kg-1)-induced hypothermia and to potentiate TRH (40 mg kg-1)-induced hyperthermia in mice. While both NA uptake inhibitors antagonized the action of H 77/77, maprotiline being weaker than desipramine, femoxetine and citalopram were inactive. However, in contrast to citalopram, femoxetine was active in the other tests, being about twice as weak as maprotiline, which itself was several times weaker than desipramine in those tests. On the basis of the results obtained it is concluded that functional in-vivo tests for NA uptake inhibitors are more sensitive than the H 77/77 biochemical test; moreover, femoxetine, which in-vitro studies is less selective than citalopram, may inhibit the uptake of NA in-vivo.

Animals↗
PubMed1986

Plasma 3,4-dihydroxyphenylethyleneglycol and therapeutic response to maprotiline and indalpine in major depression.

Plasma levels of free and conjugated 3,4-dihydroxyphenylethyleneglycol (DOPEG), the main deaminated metabolite of norepinephrine, were assayed in 48 depressed patients before initiating a treatment with either maprotiline, an inhibitor of norepinephrine reuptake, or indalpine, a specific inhibitor of serotonin reuptake. The two groups of depressed patients were comparable. The therapeutic effect was evaluated by using the Hamilton Rating Scale for Depression. No difference in pretreatment plasma free and conjugated DOPEG levels was found between the responders and the nonresponders to maprotiline or indalpine. Neither was there any difference in the pretreatment levels of plasma free DOPEG between the two groups of responders and the two groups of nonresponders to either drug. Finally, there was no difference in the therapeutic response to maprotiline or to indalpine between the patients with high and low plasma DOPEG levels before treatment. These results indicate that there is no relationship between the initial plasma levels of DOPEG in depressed patients and their therapeutic response to a norepinephrine or a serotonin reuptake blocker.

Adult↗