QuickView for Maprotiline (compound)

Summary
General Info

PubChem

PubChem Compound 198375

Name:	Maprotiline
PubChem Compound ID:	198375
Description:	A bridged-ring tetracyclic antidepressant that is both mechanistically and functionally similar to the tricyclic antidepressants, including side effects associated with its use.
Molecular formula:	C₂₁H₂₇NO₃S
Molecular weight:	373.51 g/mol
Synonyms:	N-Methyl-9,10-ethanoanthracene-9(10H)-propanamine methanesulfonate; 10262-69-8; Maprotiline methanesulfonate; EINECS 261-488-0; 58902-67-3; Methyl(propyl-9,10-ethano-9(10H)-anthryl)ammonium methanesulphonate; 9,10-Ethanoanthracene-9(10H)-propanamine, N-methyl-, methanesulfonate

DrugBank

Identification

Name:	Maprotiline
Name (isomeric):	DB00934
Drug Type:	small molecule
Description:	A bridged-ring tetracyclic antidepressant that is both mechanistically and functionally similar to the tricyclic antidepressants, including side effects associated with its use.
Synonyms:	Maprotilinum [INN-Latin]; Maprotiline Hcl; Maprotilina [INN-Spanish]; Maprotylina [Polish]
Brand:	Ludiomil, Deprilept, Psymion
Category:	Antidepressants, Adrenergic Uptake Inhibitors, Antidepressive Agents, Second-Generation
CAS number:	10262-69-8

Pharmacology

Indication:	For treatment of depression, including the depressed phase of bipolar depression, psychotic depression, and involutional melancholia, and may also be helpful in treating certain patients suffering severe depressive neurosis.
Pharmacology:	Maprotiline is a tetracyclic antidepressant. Although its main therapeutic use is in the treatment of depression, it has also been shown to exert a sedative effect on the anxiety component that often accompanies depression. In one sleep study, it was shown that maprotiline increases the duration of the REM sleep phase in depressed patients, compare... show more » Maprotiline is a tetracyclic antidepressant. Although its main therapeutic use is in the treatment of depression, it has also been shown to exert a sedative effect on the anxiety component that often accompanies depression. In one sleep study, it was shown that maprotiline increases the duration of the REM sleep phase in depressed patients, compared to imipramine which reduced the REM sleep phase. Maprotiline is a strong inhibitor of noradrenaline reuptake in the brain and peripheral tissues, however it is worthy to note that it is a weak inhibitor of serotonergic uptake. In addition, it displays strong antihistaminic action (which may explain its sedative effects) as well as weak anticholinergic action. Maprotiline also has lower alpha adrenergic blocking activity than amitriptyline. show less «
Mechanism of Action:	Maprotiline exerts its antidepressant action by inhibition of presynaptic uptake of catecholamines, thereby increasing their concentration at the synaptic clefts of the brain. In single doses, the effect of maprotiline on the EEG revealed a rise in the alpha-wave density, a reduction of the alpha-wave frequency and an increase in the alpha-wave amp... show more » Maprotiline exerts its antidepressant action by inhibition of presynaptic uptake of catecholamines, thereby increasing their concentration at the synaptic clefts of the brain. In single doses, the effect of maprotiline on the EEG revealed a rise in the alpha-wave density, a reduction of the alpha-wave frequency and an increase in the alpha-wave amplitude. However, as with other tricyclic antidepressants, maprotiline lowers the convulsive threshold. Maprotiline acts as an antagonist at central presynaptic α₂-adrenergic inhibitory autoreceptors and hetero-receptors, an action that is postulated to result in an increase in central noradrenergic and serotonergic activity. Maprotiline is also a moderate peripheral α₁ adrenergic antagonist, which may explain the occasional orthostatic hypotension reported in association with its use. Maprotiline also inhibits the amine transporter, delaying the reuptake of noradrenaline and norepinephrine. Lastly, maprotiline is a strong inhibitor of the histamine H₁ receptor, which explains its sedative actions. show less «
Absorption:	Slowly, but completely absorbed from the GI tract following oral administration.
Protein binding:	88%
Biotransformation:	Hepatic. Maprotiline is metabolized by N-demethylation, deamination, aliphatic and aromatic hydroxylations and by formation of aromatic methoxy derivatives. It is slowly metabolized primarily to desmethylmaprotiline, a pharmacologically active metabolite. Desmethylmaprotiline may undergo further metabolism to maprotiline-N-oxide.
Route of elimination:	Approximately 60% of a single orally administered dose is excreted in urine as conjugated metabolites within 21 days; 30% is eliminated in feces.
Half Life:	Average ~ 51 hours (range: 27-58 hours)
Toxicity:	LD₅₀=~900 mg/kg (Orally in rats); LD₅₀=90 mg/kg (Orally in women); Signs of overdose include motor unrest, muscular twitching and rigidity, tremor, ataxia, convulsions, hyperpyrexia, vertigo, mydriasis, vomiting, cyanosis, hypotension, shock, tachycardia, cardiac arrhythmias, impaired cardiac conduction, respiratory depression, and disturbances of consciousness up to deep coma.
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Take without regard to meals. Limit caffeine intake.

Drug interaction:

Trimethobenzamide	Trimethobenzamide and Maprotiline, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Tramadol	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Lumefantrine	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Venlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Donepezil	Possible antagonism of action

Trimethobenzamide	Trimethobenzamide and Maprotiline, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Tramadol	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Lumefantrine	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Venlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Donepezil	Possible antagonism of action
Trospium	Trospium and Maprotiline, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Zuclopenthixol	Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Trazodone	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Zolmitriptan	Use of two serotonin modulators, such as zolmitriptan and maprotiline, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
Desvenlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Mesoridazine	Increased risk of cardiotoxicity and arrhythmias
Tranylcypromine	Maprotiline may increase the adverse effects of the MAO inhibitor, Tranylcypromine. These agents should not be administered within 14 days of each other.
Thiothixene	May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Thioridazine	Increased risk of cardiotoxicity and arrhythmias
Tacrine	The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Maprotiline, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Vorinostat	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Galantamine	Possible antagonism of action
Triprolidine	Triprolidine and Maprotiline, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
Propranolol	Propranolol increases the serum levels of cisapride
Ziprasidone	Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Artemether	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Terbinafine	Terbinafine may reduce the metabolism and clearance of Maprotiline. Consider alternate therapy or monitor for therapeutic/adverse effects of Maprotiline if Terbinafine is initiated, discontinued or dose changed.
Tacrolimus	Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Toremifene	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Rivastigmine	Possible antagonism of action
Trimipramine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Cisapride	Increased risk of cardiotoxicity and arrhythmias
Voriconazole	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

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Targets

Sodium-dependent noradrenaline transporter

Histamine H1 receptor

Muscarinic acetylcholine receptor M1

Muscarinic acetylcholine receptor M2

Muscarinic acetylcholine receptor M3

Muscarinic acetylcholine receptor M4

Muscarinic acetylcholine receptor M5

Alpha-1A adrenergic receptor

Enzymes

Cytochrome P450 2D6

Cytochrome P450 1A2

Transporters

Multidrug resistance protein 1

Carriers

Alpha-1-acid glycoprotein 1