methyl(3-{tetracyclo[6.6.2.02,7.09,14]hexadeca-2,4,6,9(14),10,12-hexaen-1-yl}propyl)amine

• ChemBase ID: 810
• Molecular Formular: C20H23N
• Molecular Mass: 277.40332
• Monoisotopic Mass: 277.18304974
• SMILES: N(CCCC12CCC(c3c1cccc3)c1c2cccc1)C
• Canonical SMILES: CNCCCC12CCC(c3c1cccc3)c1c2cccc1
• 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
• InChIKey: QSLMDECMDJKHMQ-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: methyl(3-{tetracyclo[6.6.2.0^2,^7.0^9,^1^4]hexadeca-2,4,6,9(14),10,12-hexaen-1-yl}propyl)amine; methyl(3-{tetracyclo[6.6.2.0^2,^7.0^9,^1^4]hexadeca-2,4,6,9,11,13-hexaen-1-yl}propyl)amine; 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
• IUPAC Traditional name: methyl(3-{tetracyclo[6.6.2.0^2,^7.0^9,^1^4]hexadeca-2,4,6,9(14),10,12-hexaen-1-yl}propyl)amine; maprotiline
• Brand Name: Deprilept; Ludiomil; Psymion
• Synonyms: N-Methyl-9,10-ethanoanthracene-9(10H)-propanamine Hydrochloride; N-Methyl-9,10-ethanoanthracene-9(10H)-propylamine Hydrochloride; Ba-34276; Deprilept; Ludiomil; Psymion; Maprotiline Hydrochloride; Maprotilina [INN-Spanish]; Maprotiline Hcl; Maprotilinum [INN-Latin]; Maprotylina [Polish]; Maprotiline

Database IDs

• CAS Number: 10262-69-8; 10347-81-6
• PubChem SID: 46508358; 160964273
• PubChem CID: 4011
• ATC CODE: N06AA21
• CHEMBL: 21731
• Chemspider ID: 3871
• DrugBank ID: DB00934
• IUPHAR ligand ID: 2402
• KEGG ID: D02566
• Unique Ingredient Identifier: 2U1W68TROF
• Wikipedia Title: Maprotiline
• Medline Plus: a682158

CALCULATED PROPERTIES

JChem

• H Acceptors: 1
• H Donor: 1
• LogD (pH = 5.5): 1.1368963
• LogD (pH = 7.4): 1.4832375
• Log P: 4.3721046
• Molar Refractivity: 99.3017 cm^3
• Polarizability: 34.660324 Å^3
• Polar Surface Area: 12.03 Å^2
• Rotatable Bonds: 4
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 4.89
• LOG S: -6.27
• Solubility (Water): 1.50e-04 g/l

PROPERTIES

Physical Property

• Solubility: Chloroform; DMSO; Methanol; Slightly soluble
• Apperance: White Solid
• Melting Point: 241-243°C
• Hydrophobicity(logP): 5.1

Safety Information

• Storage Condition: Refrigerator

Pharmacology Properties

• Admin Routes: oral, intramuscular, intravenous (infusion)
• Bioavailability: 66 to 70%
• Excretion: biliar (30%) and urine (57%) as gluconurides, 3 to 4% as unchanged drug
• Half Life: 27-58 hours
• Metabolism: hepatic
• Protein Bound: 88%
• Legal Status: Rx-only (not a controlled substance)
• Pregnancy Category: Sufficient data does not exist. Exert caution.

DETAILS

DrugBank - DB00934

• Drug 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.
• 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, 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.
• 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
• 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.
• Absorption: Slowly, but completely absorbed from the GI tract following oral administration.
• Half Life: Average ~ 51 hours (range: 27-58 hours)
• Protein Binding: 88%
• Elimination: Approximately 60% of a single orally administered dose is excreted in urine as conjugated metabolites within 21 days; 30% is eliminated in feces.
• 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.
• External Links: Wikipedia; Drugs.com

Toronto Research Chemicals - M188000

Antidepressant.

REFERENCES

• Pinder, R.M., et al.: Drugs, 13, 321 (1977)
• Suh, SK., et al.: Anal. Profiles Drug Subs., 15, 393 (1977)
• Berjukow, S., et al.: J. Biol. Chem., 274, 6154 (1977)
• Zahradnikova, A., et al.: J. Pharmacol. Exp Ther., 322, 638 (1977)