Maprotiline

Structural formula
General
Non-proprietary name	Maprotiline
other names	N -Methyl-9,10-ethanoanthracene-9 (10 H ) -propanamine ( IUPAC )
Molecular formula	C 20 H 23 N
External identifiers / databases
ECHA InfoCard	100.030.532
PubChem	4011
DrugBank	DB00934
Wikidata	Q418361
Drug information
ATC code	N06 AA21
Drug class	Tetracyclic antidepressant
properties
Molar mass	277.41 g · mol -1
Melting point	93 ° C (maprotiline) ; 230–232 ° C (maprotiline hydrochloride ) ;
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 302
	P: no P-phrases
Toxicological data	760 mg kg −1 ( LD 50 , rat , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Maprotiline is a drug from the group of tetracyclic antidepressants that is used in psychiatry to treat depression .

Pharmacological properties

Maprotiline shows a strong inhibition of the reuptake of noradrenaline from the synaptic gap , but no significant inhibition of serotonin . It also blocks

strong histamine H ₁ -
moderate serotonin-5-HT _2A -
weak α ₁ -adrenoceptors
and very weakly muscarinic M ₁ acetylcholine receptors .

The hardly detectable anticholinergic effect offers an advantage over tricyclic antidepressants , because it results in fewer undesirable effects on the autonomic nervous system . Maprotiline also acts as a FIASMA (functional inhibitor of acid sphingomyelinase ).

The half-life of maprotiline is 43 hours and that of its active metabolite is 40 hours.

Indications

Maprotilin is approved for the treatment of depressive illnesses .

Contraindications

Maprotilin must not be used in previously damaged hearts ( conduction disorders ), increased tendency to convulsions and in children and adolescents. After previous MAO inhibitor treatment, a safety interval of at least 2 weeks must be observed.

Use during pregnancy and breastfeeding

There is insufficient experience with the use of maprotiline in humans during pregnancy. The safety of use during pregnancy has not been established. Isolated cases suggesting a possible association between maprotiline and adverse effects on the human fetus have been reported. The use of maprotiline during pregnancy should be avoided unless the benefits of treatment clearly outweigh the risks to the fetus. Since newborns whose mothers take maprotiline until birth may experience symptoms such as dyspnoea, lethargy, irritability, tachycardia, hypotension, convulsions, tremors and hypothermia during the first few hours or days, if the clinical condition allows it - Consider stopping maprotiline at least 7 weeks before the expected due date.

Side effects

Common undesirable effects of maprotiline include

Tiredness, lightheadedness and dizziness
anticholinergic effects
- Dry mouth
- Accommodation disorders, hot flashes
- Constipation, urinary retention
- Restlessness, agitation, trouble sleeping and nightmares
- Fear, aggressiveness
Nausea and vomiting
a headache
Weight gain
Libido and erectile dysfunction.

Rare, but sometimes dangerous, side effects of maprotiline are

Blood pressure fluctuations , cardiac conduction disorders with EKG changes (such as a prolongation of the QTc time )
pharmacogenic delirium , hallucinations and induction of manic or psychotic states
Syncope , seizures , dyskinesias
Alveolitis , vasculitis
Drug eruption of the skin and photosensitivity
SIADH , galactorrhea , gynecomastia
Blood formation disorders ( thrombopenia , agranulocytosis ), liver damage and hepatitis .

Dosage forms, dosage

Maprotiline is available as a tablet for oral use and as a solution for injection . The active ingredient maprotiline hydrochloride is contained in the tablets, while maprotiline mesylate , the salt of methanesulfonic acid , is contained in the injection solutions.

In order to avoid unpleasant side effects, the dose should be gradually started with 3 × 25 mg and max. can be increased to 150 mg (stationary: 225 mg). Therapy should be discontinued gradually over a period of 4–6 weeks.

Trade names

Monopreparations

Ludiomil (D, A, CH), Maprolu (D) and as a generic (D)

Web links

Swiss drug compendium : Maprotiline preparations

Individual evidence

↑ ^a ^b Entry on maprotiline in the ChemIDplus database of the United States National Library of Medicine (NLM) .
^ The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals . 14th edition, 2006, p. 993, ISBN 978-0-911910-00-1 .
↑ ^a ^b Data sheet Maprotiline hydrochloride from Sigma-Aldrich , accessed on April 9, 2011 ( PDF ).
↑ Harald Schmidt (Ed.), Founded by Claus-Jürgen Estler: Pharmakologie und Toxikologie. 6th edition Schattauer, Stuttgart a. New York 2007. p. 241.
↑ Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, Mühle C, Terfloth L, Groemer T, Spitzer G, Liedl K, Gulbins E, Tripal P: Identification of novel functional inhibitors of acid sphingomyelinase . In: PLoS ONE . 6, No. 8, 2011, p. E23852. doi : 10.1371 / journal.pone.0023852 .
^ Volkhard Kurowski: Intoxications. In: Jörg Braun, Roland Preuss (Ed.): Clinic Guide Intensive Care Medicine. 9th edition. Elsevier, Munich 2016, ISBN 978-3-437-23763-8 , pp. 673-706, here: p. 684 ( tetracyclic antidepressants ).
↑ German specialized information: Ludiomil®; Status: May 2006.
↑ Torsten Kratz, Albert Diefenbacher: Psychopharmacotherapy in old age. Avoidance of drug interactions and polypharmacy. In: Deutsches Ärzteblatt. Volume 116, Issue 29 f. (July 22) 2019, pp. 508-517, p. 512.

[ChemIDplus-1] Entry on maprotiline in the ChemIDplus database of the United States National Library of Medicine (NLM) .

[MerckIndex-2] The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals . 14th edition, 2006, p. 993, ISBN 978-0-911910-00-1 .

[Sigma-3] Data sheet Maprotiline hydrochloride from Sigma-Aldrich , accessed on April 9, 2011 ( PDF ).

[4] Harald Schmidt (Ed.), Founded by Claus-Jürgen Estler: Pharmakologie und Toxikologie. 6th edition Schattauer, Stuttgart a. New York 2007. p. 241.

[pmid18504571-5] Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, Mühle C, Terfloth L, Groemer T, Spitzer G, Liedl K, Gulbins E, Tripal P: Identification of novel functional inhibitors of acid sphingomyelinase . In: PLoS ONE . 6, No. 8, 2011, p. E23852. doi : 10.1371 / journal.pone.0023852 .

[6] Volkhard Kurowski: Intoxications. In: Jörg Braun, Roland Preuss (Ed.): Clinic Guide Intensive Care Medicine. 9th edition. Elsevier, Munich 2016, ISBN 978-3-437-23763-8 , pp. 673-706, here: p. 684 ( tetracyclic antidepressants ).

[7] German specialized information: Ludiomil®; Status: May 2006.

[8] Torsten Kratz, Albert Diefenbacher: Psychopharmacotherapy in old age. Avoidance of drug interactions and polypharmacy. In: Deutsches Ärzteblatt. Volume 116, Issue 29 f. (July 22) 2019, pp. 508-517, p. 512.