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PubMed1979

[Clinical and biochemical contributions on the action of maprotiline and clomipramine in depressive states (preliminary observation)].

This study has been conducted on 17 patients suffering from neurotic and psychotic depressions, who had not received a pharmacological antidepressive therapy since at least 1 month. 6 patients suffering from psychotic depression were treated with 100 mg clomipramine i.v. daily for 20 days; 11 patients, 7 of whom suffered from psychotic depression and 4 from neurotic depression, were treated with 150 mg maprotiline i.v. daily for 20 days. In both groups the therapy has been continued orally. In 17 patients a remarkable improvement and even in some cases complete recovery has been obtained. The two psychotropic antidepressive drugs are, furthermore, both active in the same symptoms. The determination of serotonin in human platelets confirms the strong inhibition of its re-uptake by clomipramine and the absence of re-uptake of 5-HT with maprotiline. A constant and progressive increase of 5-HIAA was noted in patients treated with clomipramine. This increase may be considered as a consequence of the increased metabolism of the larger quantity of 5-HT used by the central synapses. The interpretation of the increased levels of 5-HIAA in patients treated with maprotiline is more difficult. Further trials, for instance on the plasmatic tryptophan level, will perhaps solve the problem.

Adult↗
PubMed1979

[Clinical and biochemical contributions on the effect of maprotiline and clomipramine in depressive states (preliminary observation)].

This study has been conducted on 17 patients suffering from neurotic and psychotic depressions, who had not received a pharmacological antidepressive therapy since at least 1 month. 6 patients suffering from psychotic depression were treated with 100 mg clomipramine i.v. daily for 20 days; 11 patients, 7 of whom suffered from psychotic depression and 4 from neurotic depression, were treated with 150 mg maprotiline i.v. daily for 20 days. In both groups the therapy has been continued orally. In 17 patients a remarkable improvement and even in some cases complete recovery has been obtained. The two psychotropic antidepressive drugs are, furthermore, both active in the same symptoms. The determination of serotonin in human platelets confirms the strong inhibition of its re-uptake by clomipramine and the absence of re-uptake of 5-HT with maprotiline. A constant and progressive increase of 5-HIAA was noted in patients treated with clomipramine. This increase may be considered as a consequence of the increased metabolism of the larger quantitity of 5-HT used by the central synapses. The interpretation of the increased levels of 5-HIAA in patients treated with maprotiline is more difficult. Further trials, for instance on the plasmatic tryptophan level, will perhaps solve the problem.

Adjustment Disorders↗
PubMed1998

[A case of allergic cross reaction between tricyclic antidepressants and maprotiline].

Although a 76-year-old woman with a diagnosis of depression began a course of maprotiline, the drug was discontinued after 14 days when she developed a rash. She was started on lofepramine in substitution for maprotiline. Four years later, lofepramine treatment was stopped and to amoxapine treatment introduced due to the aggravation of depressive symptoms. On the second day of this regimen, she developed a pruritic rash. She stopped the medication immediately. Because the rash disappeared gradually, lofepramine treatment was restarted. But her recovery was restrained and new skin lesions developed. Again, she stopped the medication, and the rash cleared within several days. This case suggests the existence of cross-allergenicity between tricyclic antidepressants and maprotiline.

Aged↗
PubMed1986

Maprotiline treatment in depression. A perspective on seizures.

Eleven McLean Hospital (Belmont, Mass) depressed patients who experienced seizures while receiving maprotiline hydrochloride are presented, as are data on 87 cases reported to the manufacturer (Ciba-Geigy). Most seizures occurred at high dosages, sometimes after many weeks at a stable dose, but neither rapid dosage escalation nor high drug plasma levels seemed related to seizure occurrence. Our experience suggests that a long-acting metabolite might be responsible for seizures. Ten of the 11 McLean Hospital seizures occurred in patients receiving dosages outside of the since-revised current dosage guidelines, as did 60% of the seizures reported to the company. Data in this study suggest that reductions in maximum dosage of maprotiline prescribed after the initial six weeks of treatment could result in a further decrease in risk of seizures beyond that obtained from previous alterations in regimens.

Adult↗
PubMed2000

Spectrofluorimetric and isotachophoretic determination of maprotiline in human blood serum.

Maprotiline determination in blood serum samples was investigated by the use of both capillary isotachophoresis and spectrofluorimetric techniques. The analyte had to be enriched before determination and extraction with n-heptane was used for this purpose. The preliminary separation enabled the determination of maprotiline in blood serum at therapeutic concentration levels.

Electrophoresis↗
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↗
PubMed1980

Comparison of single-dose pharmacokinetics of imipramine and maprotiline in the elderly.

Pharmacokinetic profiles of imipramine and a newer tetracyclic antidepressant, maprotiline, were studied in elderly (75-83 years of age) subjects who were given a single oral dose of 125 and 175 mg, respectively, of these drugs. The apparent elimination half-life of imipramine was 20.8-34.9h (means 26.4h), its biovailability (F) was 40-64% (means 57%), and the apparent plasma clearance was from 0.27-0.57h/kg (mean 0.41h/kg). Maprotiline had a longer half-life (mean 31.5h range 20.6-51.8h, but its bioavailability (mean 50%) and plasma clearance (mean 0.49h/kg) values were in the range similar to those seen after imipramine. It appears that the elimination half-life of imipramine is longer and its plasma clearance is markedly reduced in elderly subjects when compared to values reported in young adults. Subjective clinical side effects were minimal with the two drugs. However, alterations in heart rate, blood pressure, or electrocardiogram occurred in all subjects. This suggests that caution should be exercised before initiating and during the treatment of elderly patients with these antidepressant drugs.

Aged↗
PubMed1980

An evaluation of maprotiline intravenous kinetics and comparison of two oral doses.

The kinetics of maprotiline have been evaluated in six normal volunteers following rapid intravenous administration of 75 mg. Blood levels could be resolved using a biexponential equation. Mean estimates of half-life, volume of distribution and systemic clearance were 40 +/- 15 h, 51.7 +/- 18.01/kg and 0.92 +/- 0.24/kg/h, respectively. Blood/plasma concentrations varied between subjects from 0.77 to 1.64. A comparison of the bioavailability of two oral doses (a 75 mg tablet and three 25 mg tablets) was carried out in the same volunteers. No significant difference was observed between the maprotiline concentrations obtained for the two doses at sampling times up to 26 h. No significant difference was found in the area under the concentration vs. time curves for the two doses. Equivalent bioavailability can be assumed. On the basis of the intravenous injection study, systemic bioavailability averaged 66% and 70% for the 75 mg and three 25 mg tablets respectively.

Administration, Oral↗
PubMed1988

Interaction of alcohol with maprotiline or nomifensine: echocardiographic and psychometric effects.

Eight healthy volunteers received low doses of maprotiline and nomifensine up to 50 mg b.d. for 15 days in a double-blind, cross-over, placebo controlled study, during which echocardiography and psychomotor testing were carried out before and after the intake of alcohol 1 g/kg. Maprotiline increased heart rate and cardiac output and reduced peripheral resistance compared to placebo and nomifensine. Nomifensine alone was associated with a slight decrease in heart rate. Alcohol alone caused a significant increase in diastolic blood pressure, but did not otherwise modify the cardiovascular measures. The antidepressants did not augment the effects of alcohol. Antidepressants alone had no effect on psychomotor skills, but alcohol always impaired performance. No additional effects of alcohol were produced by the antidepressants. It appears that practically important peripheral or central consequences are unlikely to follow drinking a moderate amount of alcohol during regular therapy with low therapeutic doses of catecholamine reuptake inhibiting antidepressants. Experimental studies of the interaction of antidepressants and alcohol in patients with chronic heart disease seem to be justified.

Adolescent↗
PubMed1992

Antidepressants and cognition: comparative effects of moclobemide, viloxazine and maprotiline.

The respective effects of three antidepressant drugs (moclobemide, 450 mg/j; viloxazine, 300 mg/j; maprotiline, 150 mg/j) on vigilance, attention, and memory were compared. Young depressed outpatients (n = 46) entered a double-blind, randomized, monocentre clinical trial lasting for 6 weeks. Drug actions were assessed through the regular determination of critical flicker fusion point (CFF), reaction times (SRT), and a battery to measure memory components. None of the three drugs caused deterioration in cognitive functions. On the other hand, moclobemide improved both vigilance and attention (CFF, SRT) and some crucial components of memory (general memory scores, delayed word recall, recognition of familiar faces). This effect was rapid, stable, and superior to those of viloxazine and maprotiline. It may be explained by moclobemide's selective and reversible inhibition of monoamine oxidase A, as well as by the lack of any anticholinergic action.

Adult↗
PubMed1992

Reversal of stress-induced anhedonia by the atypical antidepressants, fluoxetine and maprotiline.

Chronic exposure to mild unpredictable stress has previously been found to depress the consumption of palatable sweet solutions. In the present study this effect was reversed by chronic (9 weeks) treatment with the atypical antidepressants, fluoxetine and maprotiline (5 mg/kg/day); the non-antidepressant chlordiazepoxide was ineffective. Stressed animals were also subsensitive to food reward in the place conditioning procedure; however, fluoxetine and maprotiline treated animals showed normal place preference conditioning. Acute pretreatment with raclopride (100 micrograms/kg) selectively reversed the recovery of sucrose drinking in antidepressant-treated stressed animals. These results extend previous reports of the efficacy of tricyclic antidepressants in this paradigm, and support the hypothesis of a dopaminergic mechanism of antidepressant action.

Animals↗
PubMed1987

Changes in [3H]5-HT uptake and [3H]imipramine binding in platelets after chlorimipramine in healthy volunteers. Comparison with maprotiline and amineptine.

In the platelets of normal healthy volunteers (n = 8) taking chlorimipramine (50 mg/day) for 1 week, the saturable uptake of [3H]5-hydroxytryptamine (5-HT) was fully inhibited at the end of the week, but returned to control values after 2 weeks washout. The Bmax of [3H]imipramine binding was decreased by 63% at the end of the treatment and remained significantly decreased below control values after 1 week washout, whereas the Kd values were increased at the end of the treatment, but had returned to baseline values after 1 week washout. The time course of recovery following the administration of chlorimipramine showed some variation between subjects, but it was necessary to wait up to 4 weeks of washout before the Bmax of [3H]imipramine returned to baseline levels. In contrast, neither 1-week treatment with maprotiline (50 mg/day) nor with amineptine (100 mg/day) changed the parameters of [3H]5-HT uptake or [3H]imipramine binding in platelets from healthy volunteers. These results support the following conclusions. (1) [3H]Imipramine binding in platelets can be down-regulated by relatively low, subtherapeutic doses of chlorimipramine. (2) It is possible to dissociate [3H]imipramine binding parameters from [3H]5-HT uptake because the time course of recovery was clearly different, indicating that [3H]imipramine labels a site linked with, but different from, the 5-HT recognition site in the transporter complex. (3) A washout of antidepressants of 4 weeks may be needed when studying the parameters of [3H]imipramine binding in platelets from depressed patients if the previous medication involved chlorimipramine. For antidepressants like maprotiline or amineptine, that act through mechanisms other than inhibition of 5-HT uptake, the time of washout appears to be less critical, although it is not possible to rule out the existence of some secondary modifications influencing the 5-HT transporter complex.

Adult↗
PubMed1983

The effects of single and repeated doses of maprotiline, oxaprotiline and its enantiomers on foot-shock induced fighting in rats.

Foot-shock induced fighting behavior (SIF) in rats was tested after single and repeated dose-treatment (10 mg/kg IP twice daily for 10 days) of maprotiline, oxaprotiline and of (+)- and (-)-enantiomers of oxaprotiline. Marked facilitation of SIF was observed after repeated but not single administration of all drugs including the NA-uptake inactive (-)-enantiomer of oxaprotiline. No enhancement of SIF was seen after multiple dose-treatment with promethazine, an antihistaminic, or atropine. The mechanism of the facilitation of SIF induced by antidepressants maprotiline and oxaprotiline as well as by its enantiomers is unclear. The clear-cut dissociation of the effect of (+)- and (-)-oxaprotiline on the rate of NA-disappearance, but their similar enhancing effect on SIF challenges the assumption of a primary importance of central NA-system in this behavior. By contrast, the increase in jumping behavior recorded additionally to SIF, seems to be a great extent dependent on NA-uptake inhibiting properties of tested drugs.

Aggression↗
PubMed1994

Assay for maprotiline in human serum with improved sensitivity and selectivity.

The use of a photoreactor and fluorescence detection enables measurement of the tetracyclic antidepressant drug 3-(9,10-dihydro-9,10-ethanoanthracene-9-yl)-N-methylpropylamine (maprotiline) with a sensitivity of 100 pg/ml serum. This detection system is highly specific and enables the measurement of very low concentrations in the presence of high concentrations of other drugs that are often found in patient samples. The mean free portions of maprotiline and desmethylmaprotiline were found to be 2.2% and 1.5%, respectively.

Half-Life↗
PubMed1995

Determination of maprotiline in plasma by high-performance liquid chromatography with chemiluminescence detection.

A simple and sensitive high-performance liquid chromatographic method is described for the determination of maprotiline, an antidepressant, in plasma. After a single-step extraction from plasma (100 microliters) with n-hexaneisoamylalcohol (19:1, v/v), the drug and desipramine (internal standard) are converted into their chemiluminescent derivatives by reaction with 6-isothiocyanatobenzo[g]phthalazine-1,4(2H,3H)-dione, a new chemiluminescence derivatization reagent for amines. The derivatives are separated within 60 min on a reversed-phase column, TSKgel ODS-80, using isocratic elution with acetonitrile-100 mM acetate buffer (pH 3.2), and produced chemiluminescence by reaction with hydrogen peroxide in the presence of potassium hexacyanoferrate(III) in alkaline medium. The detection limit for maprotiline added to plasma is 0.36 pmol (0.1 ng)/ml plasma (1.5 fmol on column), at a signal-to-noise ratio of 3.

Antidepressive Agents, Second-Generation↗
PubMed1988

Maprotiline poisoning in a child.

A 6-year-old girl presented with tonic-clonic seizures and generalized convulsions lasting several minutes. A serum drug screen revealed maprotiline, and the estimated intake was 12 mg/kg. Despite initial neurologic impairment on discharge, follow-up 6 months later showed normal neurologic function in the patient. This report describes that case and discusses the toxicity associated with maprotiline and its management.

Anthracenes↗
PubMed1983

Q-T prolongation and torsades de pointes ventricular tachycardia produced by the tetracyclic antidepressant agent maprotiline.

Tricyclic antidepressant drugs such as imipramine and desipramine have long been known to produce cardiovascular side effects including sinus tachycardia, prolongation of the P-R, QRS, and Q-T intervals, and decreased T-wave amplitude. Life-threatening ventricular ectopic activity has occurred after tricyclic drug overdose. Recently, maprotiline (Ludiomil), a tetracyclic anthracene-derivative antidepressant, has become available for the treatment of affective disorders. It appears as effective as the tricyclic drugs in relieving unipolar depression. Although several studies have reported a low incidence of cardiovascular side effects, others show little difference between the tetracyclic and tricyclic drugs. This report describes a patient in whom maprotiline treatment caused Q-T prolongation and life-threatening torsades de pointes ventricular tachycardia (VT).

Aged↗