Systematic (IUPAC) name
N-Methyl- 9,10-ethanoanthracene- 9(10H)- propanamine
Clinical data
AHFS/ monograph
MedlinePlus a682158
Pregnancy cat. Sufficient data does not exist. Exert caution.
Legal status Rx-only (not a controlled substance)
Routes oral, intramuscular, intravenous (infusion)
Pharmacokinetic data
Bioavailability 66 to 70%
Protein binding 88%
Metabolism hepatic
Half-life 27-58 hours
Excretion biliar (30%) and urine (57%) as gluconurides, 3 to 4% as unchanged drug
CAS number 10262-69-8 YesY
ATC code N06AA21
PubChem CID 4011
IUPHAR ligand 2402
DrugBank DB00934
ChemSpider 3871 YesY
KEGG D02566 YesY
Chemical data
Formula C20H23N 
Mol. mass 277.403 g/mol
SMILES eMolecules & PubChem
 N(what is this?)  (verify)

Maprotiline (sold as Deprilept, Ludiomil, Psymion) is a tetracyclic antidepressant (TeCA). It is a strong norepinephrine reuptake inhibitor with only weak effects on serotonin and dopamine reuptake.

It exerts blocking effects at the following postsynaptic receptors:

  • Strong : H1
  • Moderate : 5-HT2, alpha1
  • Weak : D2, mACh

The pharmacologic profile of Maprotiline explains its antidepressant, sedative, anxiolytic, and sympathomimetic activities. Additionally, it shows a strong antagonism against Reserpine-induced effects in animal studies, as do the other 'classical' antidepressants. Although Maprotiline behaves in most regards as a 'first generation antidepressant' it is commonly referred to as 'second generation antidepressant'.

Sedation has a fast onset (the same day), while remission of the depression itself is noted usually after a latent period of one to four weeks.

Maprotiline does not improve mood in nondepressed persons.



Maprotiline was developed and has been marketed by the Swiss manufacturer Geigy (now Novartis) since the early 1980s under the brand name Ludiomil. Generics are widely available.


  • Treatment of depressions of all forms and severities (endogenous, psychotic, involutional, and neurotic)
  • Treatment of the depressive phase in bipolar depression
  • For the symptomatic relief of anxiety, tension or insomnia

N.B. The use of maprotiline in the treatment of enuresis in pediatric patients has so far not been systematically explored and its use is not recommended.



  • Hypersensitivity to Maprotiline or to other tri-/tetracyclic antidepressants
  • Hypertrophy of the prostate gland with urine hesitancy
  • Closed Angle Glaucoma

Special caution needed

  • Concomitant treatment with a MAO-Inhibitor
  • Serious impairment of liver and kidney function
  • Epilepsy and other conditions that lower the seizure threshold (active brain tumors, alcohol withdrawal, other medications)
  • Serious cardiovascular conditions (arrhythmias, heart insufficience, state after myocardial infarction etc.)
  • Treatment of patients under age 18

Pregnancy and nursing

Animal studies showed delayed bone development. Maprotiline should be used during pregnancy only if needed.

Maprotiline should not be given to nursing mothers.

Side effects

The side-effect profile is comparable to other tri-/tetracyclic antidepressants and many of the following are due to anticholinergic effects. Most often seen are:

Other uncommon side effects have been observed.

Maprotiline causes a strong initial sedation (first 2 to 3 weeks of therapy) and is therefore indicated to treat agitated patients or those with suicidal risks. It causes anticholinergic side effects (dry mouth, constipation, confusion, tachycardia) with a lower incidence than amitritypline. Originally, the manufacturer claimed that maprotiline is better tolerated than other tri-/tetracyclic drugs. However, seizures, leukopenia and skin reactions occur more often with maprotiline than with comparable drugs like amitriptyline.

Necessary examinations during therapy

All patients should have frequent blood pressure checks and periodic white blood cell counts. At-risk patients need regular EKG and EEG monitoring as well.

Suicidal patients

Patients with suicidal thoughts, or those with previous suicidal attempts, should be monitored closely under treatment with Maprotiline. The decision may be made to hospitalize high risk patients until remission or to prescribe an additional sedating drug like a benzodiazepine or Chlorprothixene for 2–4 weeks of initial treatment with Maprotiline (until significant remission).

Generally, many antidepressants (SSRIs, other tricyclic drugs) have been shown to cause a significant higher rate of suicidal thoughts and suicidal attempts in patients under 18 yrs. of age compared to placebo. It is not known if Maprotiline shares this risk, so cautionary measures are recommended.

Drug abuse and dependence

Maprotiline has no known potential for abuse and psychological dependence.

Withdrawal symptoms frequently seen when treatment with maprotiline is stopped abruptly (agitation, anxiety, insomnia, sometimes activation of mania or rebound depression) are not indicative of addiction and can be avoided by reducing the daily dose of Maprotiline gradually by approximately 25% each week. If treatment has to be stopped at once due to medical reasons, the use of a benzodiazepine (e.g. lorazepam, clonazepam, or alprazolam) for a maximum of 4 weeks as needed will usually suppress withdrawal symptoms.


Maprotiline may worsen psychotic conditions like schizophrenia and should be given with caution. The antipsychotic treatment should be continued.

Patients with bipolar affective disorder should not receive antidepressants whilst in a manic phase, as antidepressants can worsen mania.


Maprotiline has a wide range of possible interactions. Some are typical for tri-/tetracyclic antidepressants, others are caused by specific metabolic effects (e.g. high plasma-protein-binding) of Maprotiline:

  • Irreversible MAO-Inhibitors: agitation, delirium, coma, hyperpyrexia (high fever), seizures and severe changes in blood pressure. N.B. Treatment-resistant and hospitalized patients may be treated concomitantly with an MAO-Inhibitor, if they are closely monitored and if the initial dose of the MAO-Inhibitor is low.

Increased drug actions:

  • Other antidepressants, barbiturates, narcotics, sedating antihistaminics, anticonvulsive drugs, alcohol - resulting in increased central depression
  • Anticholinergics (antiparkinsonian agents, tri- and tetracyclic antidepressants) - resulting in increased anticholinergic action (dry mouth, constipation etc.)
  • Sympathomimetics (also those used in local anesthetics like Noradrenaline) : sympathomimetic effects increased (increased blood pressure, pulse rate, paleness of skin etc.)
  • Nitrates and Antihypertensives (e.g. Beta-Blockers) - increased antihypertensive action with pronounced fall in blood pressure

Decreased drug actions:

  • Guanethidine, Reserpine, Guanfacine : antihypertensive effects decreased
  • Clonidine : antihypertensive effects decreased and risk of (massive) rebound hypertension.

Other types of interaction:

  • Drugs, which induce certain enzymes in the liver, e.g. Barbiturates, Phenytoin, Carbamazepine and oral anticonceptive drugs, enhance the elimination of Maprotiline and decrease its antidepressant effects. Additionally the blood-concentrations of Phenytoin or Carbamazepine may be increased, leading to a higher incidents of side effects.
  • The concomitant use of Maprotiline and neuroleptics can lead to increased Maprotiline blood-levels and to seizures. Combining Maprotiline and Thioridazine could induce severe arrhythmias.
  • Additionally, increased blood-levels of Maprotiline are possible, if certain beta-blocking agents (e.g. Propranolol) are given concomitantly.
  • Maprotiline may amplify the actions of coumarin-type anticogulants (e.g. Warfarin, Phenprocoumon). The plasma-prothrombin-activity must be assessed closely in order to avoid overt bleedings.
  • Maprotiline can increase the actions of oral antidiabetic drugs (sulfonylureas) and Insulin. Diabetic patients should have regular assessments of their blood-glucose-levels.
  • The concomitant application with Fluoxetine or Fluvoxamine may lead to significantly increased plasma-levels of Maprotiline with a high incidence of Maprotiline side effects. Due to the long half-lives of Fluoxetine and Fluvoxamine this effect may persist.


Maprotilin synthesis.png
The first step in the preparation of the antidepressant maprotiline takes advantage of the acidity of anthrone protons for incorporation of the side chain. Thus treatment of (1) with ethyl acrylate and a relatively mild base leads to the Michael adduct; saponification of the ester group gives the corresponding acid (2). The ketone group is then reduced by means of zinc and ammonium hydroxide. Dehydration of the first-formed alcohol under acidic conditions leads to the formation of fully aromatic anthracene (3). Diels–Alder addition of ethylene under high pressure leads to the addition across the 9,10 positions and the formation of the central 2,2,2-bicyclooctyl moiety (4). The final steps involve the construction of the typical antidepressant side chain. The acid in (4) is thus converted to an acid chloride and that function reacted with methylamine to form the amide (5). Reduction to a secondary amine completes the synthesis of (6).[1]


Symptoms of overdose may include flushing, fast or irregular heartbeat, dry mouth, drowsiness, confusion, agitation, enlarged pupils, seizures, and loss of consciousness.

Drugs commonly used to treat overdose are Physostigmine to counteract central and peripher anticholinergic effects and Diazepam to control convulsion. Symptomatic measures are stabilization of blood pressure and correction of water- and electrolyt-deficits. Lidocaine can be given intravenously in small doses against cardial arrhythmias.

Due to milder anticholinergic and cardiotoxic effects of Maprotiline the acute lethal dose may be higher compared with other classical antidepressants (e.g. Amitriptyline, Doxepin). Maprotiline is more toxic than the other tetracyclic drugs Mianserin and Mirtazapine.


  • Oral: Usually, treatment is started with 3 times 25 mg or 75 mg in a single dose at bedtime. The daily dose is gradually increased to 150 mg daily (2 times 75 mg or 3 times 50 mg). Doses up to 225 mg are possible, but carry the risk of a higher incidence of seizures.
  • Parenteral: i.m.-injections and slow iv.-infusions with total daily doses of 75 to 150 mg are possible. Parenteral treatment may lead to an earlier onset of action of Maprotiline but may also be associated with an increased risk of seizures.

Dose forms

  • Coated Tablets, 10 mg, 25 mg, 50 mg, and 75 mg
  • Injectable concentrate, 25 mg

Brand names

  • Ludiomil, Deprilept Psymion
  • Generics

External links


  1. ^ Wilhelm, M.; Schmidt, P.; Helv. Chim. Acta 1969, 52, 1385.
  • B. Bandelow, S. Bleich, S. Kropp : Handbuch Psychopharmaka (German), 2nd. edition, 2004
  • Benkert, Hippius : Kompendium der Psychiatrischen Pharmakotherapie (German), 4th. edition, 2003