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| Name | Maprotiline | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Accession Number | DB00934 (APRD00747) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Type | small molecule | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Groups | approved | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Description | Maprotiline is a tetracyclic antidepressant with similar pharmacological properties to tricyclic antidepressants (TCAs). Similar to TCAs, maprotiline inhibits neuronal norepinephrine reuptake, possesses some anticholinergic activity, and does not affect monoamine oxidase activity. It differs from TCAs in that it does not appear to block serotonin reuptake. Maprotiline may be used to treat depressive affective disorders, including dysthymic disorder (depressive neurosis) and major depressive disorder. Maprotiline is effective at reducing symptoms of anxiety associated with depression. |
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| Structure |
Download: MOL | SDF | SMILES | InChI Display: 2D Structure | 3D Structure |
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| Synonyms |
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| Salts | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Brand names |
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| Brand mixtures | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| CAS number | 10262-69-8 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Weight |
Average: 277.4033 Monoisotopic: 277.183049741 |
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| Chemical Formula | C20H23N | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| InChI Key | InChIKey=QSLMDECMDJKHMQ-UHFFFAOYSA-N | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| InChI |
InChI=1S/C20H23N/c1-21-14-6-12-20-13-11-15(16-7-2-4-9-18(16)20)17-8-3-5-10-19(17)20/h2-5,7-10,15,21H,6,11-14H2,1H3
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| IUPAC Name |
methyl(3-{tetracyclo[6.6.2.0^{2,7}.0^{9,14}]hexadeca-2(7),3,5,9(14),10,12-hexaen-1-yl}propyl)amine
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| SMILES |
CNCCCC12CCC(C3=CC=CC=C13)C1=CC=CC=C21
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| Mass Spec | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Taxonomy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Kingdom | Organic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Substructures |
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| 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pharmacodynamics | 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Absorption | Slowly, but completely absorbed from the GI tract following oral administration. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Volume of distribution | Maprotiline and its metabolites may be detected in the lungs, liver, brain, and kidneys; lower concentrations may be found in the adrenal glands, heart and muscle. Maprotiline is readily distributed into breast milk to similar concentrations as those in maternal blood. |
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| Protein binding | 88% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Metabolism | 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) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Clearance | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Pathways | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Prices |
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational
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| Patents | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Properties | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| State | solid | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Experimental Properties |
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| Predicted Properties |
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| Synthesis Reference | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| General Reference | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| PDB Entries | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| FDA label | Not Available | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| MSDS | show (64.8 KB) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Targets |
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1. Sodium-dependent noradrenaline transporter Pharmacological action: yesActions: inhibitor Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals Organism class: humanUniProt ID: P23975 ![]() Gene: SLC6A2 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Pharmacological action: no
Actions: antagonist In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system Organism class: humanUniProt ID: P35367 ![]() Gene: HRH1 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
3. Muscarinic acetylcholine receptor M1 Pharmacological action: noActions: antagonist The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover Organism class: humanUniProt ID: P11229 ![]() Gene: CHRM1 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
4. Muscarinic acetylcholine receptor M2 Pharmacological action: noActions: antagonist The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition Organism class: humanUniProt ID: P08172 ![]() Gene: CHRM2 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
5. Muscarinic acetylcholine receptor M3 Pharmacological action: noActions: antagonist The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover Organism class: humanUniProt ID: P20309 ![]() Gene: CHRM3 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
6. Muscarinic acetylcholine receptor M4 Pharmacological action: noActions: antagonist The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase Organism class: humanUniProt ID: P08173 ![]() Gene: CHRM4 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
7. Muscarinic acetylcholine receptor M5 Pharmacological action: noActions: antagonist The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover Organism class: humanUniProt ID: P08912 ![]() Gene: CHRM5 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
8. Alpha-1A adrenergic receptor Pharmacological action: noActions: antagonist This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins Organism class: humanUniProt ID: P35348 ![]() Gene: ADRA1A ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References: |
| Enzymes |
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Actions: substrate
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants UniProt ID: P10635![]() Gene: CYP2D6 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: substrate
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen UniProt ID: P05177![]() Gene: CYP1A2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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1. Multidrug resistance protein 1 Actions: inhibitorEnergy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells UniProt ID: P08183![]() Gene: ABCB1 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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1. Alpha-1-acid glycoprotein 1 Appears to function in modulating the activity of the immune system during the acute-phase reaction UniProt ID: P02763![]() Gene: ORM1 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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