Tìm theo
Maprotiline
Các tên gọi khác (10 ) :
  • BA-34276 [as hydrochloride]
  • Deprilept
  • Ludiomil
  • Maprotilina
  • Maprotilinum
  • Maprotylina
  • Psymion
  • SID104171192
  • SID11111502
  • SID11112599
antidepressive agents second generation, adrenergic uptake inhibitors, antidepressive agents
Thuốc Gốc
Small Molecule
CAS: 10262-69-8
ATC: N06AA21
ĐG : Major Pharmaceuticals , http://www.majorpharmaceuticals.com
CTHH: C20H23N
PTK: 277.4033
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.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C20H23N
Phân tử khối
277.4033
Monoisotopic mass
277.183049741
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
InChI Key
InChIKey=QSLMDECMDJKHMQ-UHFFFAOYSA-N
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
Traditional IUPAC Name
maprotiline
SMILES
CNCCCC12CCC(C3=CC=CC=C13)C1=CC=CC=C21
Độ tan chảy
93 °C
Độ hòa tan
Slightly soluble
logP
5.1
logS
-6.3
pKa (Strongest Basic)
10.54
PSA
12.03 Å2
Refractivity
99.3 m3·mol-1
Polarizability
33.57 Å3
Rotatable Bond Count
4
H Bond Acceptor Count
1
H Bond Donor Count
1
Physiological Charge
1
Number of Rings
4
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : 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.
Cơ Chế Tác Dụng : 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. 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.
Dược Động Học :
▧ 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.
▧ 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)
Độc Tính : 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.
Chỉ Định : 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.
Tương Tác Thuốc :
  • Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Cisapride Increased risk of cardiotoxicity and arrhythmias
  • Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Donepezil Possible antagonism of action
  • Galantamine Possible antagonism of action
  • Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Mesoridazine Increased risk of cardiotoxicity and arrhythmias
  • Propranolol Propranolol increases the serum levels of cisapride
  • Rivastigmine Possible antagonism of action
  • 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.
  • Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • 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.
  • Thioridazine Increased risk of cardiotoxicity and arrhythmias
  • 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.
  • 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.
  • Tramadol Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Tranylcypromine Maprotiline may increase the adverse effects of the MAO inhibitor, Tranylcypromine. These agents should not be administered within 14 days of each other.
  • Trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Trimethobenzamide Trimethobenzamide and Maprotiline, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
  • 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.
  • 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.
  • Trospium Trospium and Maprotiline, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
  • Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Voriconazole Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
  • Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
  • Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
  • 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.
  • 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).
Liều Lượng & Cách Dùng : Tablet - Oral - 25 mg
Tablet - Oral - 50 mg
Tablet - Oral - 75 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Deprilept
  • Công ty :
    Sản phẩm biệt dược : Ludiomil
  • Công ty :
    Sản phẩm biệt dược : Psymion
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00934
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=4011
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46508358
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07107
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D02566
ChemSpider
http://www.chemspider.com/Chemical-Structure.3871.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=35228
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0378-0060-01
PharmGKB
http://www.pharmgkb.org/drug/PA450322
Wikipedia
http://en.wikipedia.org/wiki/Maprotiline
Drugs.com
http://www.drugs.com/cdi/maprotiline.html
... loading
... loading