Tìm theo
Amoxapine
Các tên gọi khác (6 ) :
  • 2-Chloro-11-(1-piperazinyl)dibenz(b,F)(1,4)oxazepine
  • Amoxapin
  • Amoxapina
  • Amoxapinum
  • Amoxepine
  • Desmethylloxapin
antidepressive agents second generation, serotonin uptake inhibitors, adrenergic uptake inhibitors, dop
Thuốc Gốc
Small Molecule
CAS: 14028-44-5
ATC: N06AA17
ĐG : Kaiser Foundation Hospital
CTHH: C17H16ClN3O
PTK: 313.781
Amoxapine, the N-demethylated derivative of the antipsychotic agent loxapine, is a dibenzoxazepine-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, amoxapine does not affect mood or arousal, but may cause sedation. In depressed individuals, amoxapine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. In addition, TCAs down-regulate cerebral cortical β-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine H1 receptors, α1-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. See toxicity section below for a complete listing of side effects. Amoxapine may be used to treat neurotic and reactive depressive disorders, endogenous and psychotic depression, and mixed symptoms of depression and anxiety or agitation.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C17H16ClN3O
Phân tử khối
313.781
Monoisotopic mass
313.098189856
InChI
InChI=1S/C17H16ClN3O/c18-12-5-6-15-13(11-12)17(21-9-7-19-8-10-21)20-14-3-1-2-4-16(14)22-15/h1-6,11,19H,7-10H2
InChI Key
InChIKey=QWGDMFLQWFTERH-UHFFFAOYSA-N
IUPAC Name
13-chloro-10-(piperazin-1-yl)-2-oxa-9-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,9,12,14-heptaene
Traditional IUPAC Name
13-chloro-10-(piperazin-1-yl)-2-oxa-9-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,9,12,14-heptaene
SMILES
ClC1=CC2=C(OC3=CC=CC=C3N=C2N2CCNCC2)C=C1
Độ tan chảy
175-176
Độ hòa tan
1.71e-01 g/l
logP
3.4
logS
-3.3
pKa (Strongest Basic)
8.83
PSA
36.86 Å2
Refractivity
89.82 m3·mol-1
Polarizability
32.82 Å3
Rotatable Bond Count
0
H Bond Acceptor Count
3
H Bond Donor Count
1
Physiological Charge
1
Number of Rings
4
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : Amoxapine is a tricyclic antidepressant of the dibenzoxazepine class, chemically distinct from the dibenzodiazepines, dibenzocycloheptenes, and dibenzoxepines. It has a mild sedative component to its action. The mechanism of its clinical action in man is not well understood. In animals, amoxapine reduced the uptake of nor-epinephirine and serotonin and blocked the response of dopamine receptors to dopamine. Amoxapine is not a monoamine oxidase inhibitor. Clinical studies have demonstrated that amoxapine has a more rapid onset of action than either amitriptyline or imipramine
Cơ Chế Tác Dụng : Amoxapine, the N-demethylated derivative of the antipsychotic agent loxapine, is a dibenzoxazepine-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, amoxapine does not affect mood or arousal, but may cause sedation. In depressed individuals, amoxapine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. In addition, TCAs down-regulate cerebral cortical β-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine H1 receptors, α1-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. See toxicity section below for a complete listing of side effects. Amoxapine may be used to treat neurotic and reactive depressive disorders, endogenous and psychotic depression, and mixed symptoms of depression and anxiety or agitation. Amoxapine acts by decreasing the reuptake of norepinephrine and serotonin (5-HT).
Dược Động Học :
▧ Absorption :
Rapidly and almost completely absorbed from the GI tract. Peak plasma concentrations occur within 1-2 hours of oral administration of a single dose.
▧ Volume of Distribution :
Widely distributed in body tissues with highest concentrations found in lungs, spleen, kidneys, heart, and brain. Lower concentrations can be detected in testes and muscle.
▧ Protein binding :
In vitro tests show that amoxapine binding to human plasma proteins is approximately 90%.
▧ Metabolism :
Amoxapine is almost completely metabolized in the liver to its major metabolite, 8-hydroxyamoxapine, and a minor metabolite, 7-hydroxyamoxapine. Both metabolites are phamacologically inactive and have half-lives of approximately 30 and 6.5 hours, respectively.
▧ Route of Elimination :
60-69% of a single orally administered dose of amoxapine is excreted in urine, principally as conjugated metabolites. 7-18% of the dose is excrete feces mainly as unconjugated metabolites. Less than 5% of the dose is excreted as unchanged drug in urine.
▧ Half Life :
8 hours
Độc Tính : Toxic manifestations of amoxapine overdosage differ significantly from those of other tricyclic antidepressants. Serious cardiovascular effects are seldom if ever observed. However, CNS effects, particularly grand mal convulsions, occur frequently, and treatment should be directed primarily toward prevention or control of seizures. Status epilepticus may develop and constitutes a neurologic emergency. Coma and acidosis are other serious complications of substantial amoxapine overdosage in some cases. Renal failure may develop two to five days after toxic overdose in patients who may appear otherwise recovered. Acute tubular necrosis with rhabdomuolysis and myolobinurla is the most common renal complication in such cases. This reaction probably occurs in less than 5% of overdose cases, and typically in those who have experienced multiple seizures.
Chỉ Định : For the relief of symptoms of depression in patients with neurotic or reactive depressive disorders as well as endogenous and psychotic depressions. May also be used to treat depression accompanied by anxiety or agitation.
Tương Tác Thuốc :
  • Altretamine Risk of severe hypotension
  • Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Atazanavir Atazanavir may increase the effect and toxicity of the tricyclic antidepressant, amoxapine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amoxapine if atazanavir if initiated, discontinued or dose changed.
  • Butabarbital Barbiturates like butabarbital may increase the metabolism of tricyclic antidepressants like amoxipine. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
  • Butalbital Barbiturates such as butalbital may increase the metabolism of tricyclic antidepressants amoxapine. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
  • Cimetidine Cimetidine may increase the effect of the tricyclic antidepressant, amoxapine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amoxapine if cimetidine is initiated, discontinued or dose changed.
  • Cisapride Increased risk of cardiotoxicity and arrhythmias
  • Clonidine The tricyclic antidepressant, amoxapine, decreases the effect of clonidine.
  • Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Dobutamine The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of dobutamine.
  • Donepezil Possible antagonism of action
  • Dopamine The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of dopamine.
  • Ephedra The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of ephedra.
  • Ephedrine The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of ephedrine.
  • Epinephrine The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of epinephrine.
  • Fenoterol The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of fenoterol.
  • Fluoxetine The SSRI, fluoxetine, may increase the serum concentration of the tricyclic antidepressant, amoxapine, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of amoxapine if fluoxetine is initiated, discontinued or dose changed.
  • Fluvoxamine The SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, amoxapine, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of amoxapine if fluvoxamine is initiated, discontinued or dose changed.
  • Galantamine Possible antagonism of action
  • Grepafloxacin Increased risk of cardiotoxicity and arrhythmias
  • Guanethidine The tricyclic antidepressant, amoxapine, decreases the effect of guanethidine.
  • Isocarboxazid Possibility of severe adverse effects
  • Isoprenaline The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of isoproterenol.
  • Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Mephentermine The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of mephentermine.
  • Metaraminol The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of metaraminol.
  • Methoxamine The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of methoxamine.
  • Moclobemide Possible severe adverse reaction with this combination
  • Norepinephrine The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of norepinephrine.
  • Orciprenaline The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of orciprenaline.
  • Phenelzine Possibility of severe adverse effects
  • Phenylephrine The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of phenylephrine.
  • Phenylpropanolamine The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of phenylpropanolamine.
  • Pirbuterol The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of pirbuterol.
  • Procaterol The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of procaterol.
  • Pseudoephedrine The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of pseudoephedrine.
  • Rasagiline Possibility of severe adverse effects
  • Rifabutin The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, amoxapine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amoxapine if rifabutin is initiated, discontinued or dose changed.
  • Rifampicin The rifamycin, rifampin, may decrease the effect of the tricyclic antidepressant, amoxapine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amoxapine if rifampin is initiated, discontinued or dose changed.
  • Ritonavir Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, amoxapine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amoxapine if ritonavir if initiated, discontinued or dose changed.
  • Rivastigmine Possible antagonism of action
  • Salbutamol The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of salbutamol.
  • Sibutramine Increased risk of CNS adverse effects
  • Sparfloxacin Increased risk of cardiotoxicity and arrhythmias
  • Tacrine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Amoxapine, 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 Amoxapine. Consider alternate therapy or monitor for therapeutic/adverse effects of Amoxapine if Terbinafine is initiated, discontinued or dose changed.
  • Terbutaline The tricyclic antidepressant, amoxapine, increases the sympathomimetic effect of terbutaline.
  • Terfenadine 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 Tramadol increases the risk of serotonin syndrome and seizures.
  • Tranylcypromine Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.
  • Trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Trimethobenzamide Trimethobenzamide and Amoxapine, 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 Amoxapine, 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 Amoxapine, 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 amoxapine, 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 - 100 mg
Tablet - Oral - 150 mg
Tablet - Oral - 25 mg
Tablet - Oral - 50 mg
Dữ Kiện Thương Mại
Giá thị trường
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    Sản phẩm biệt dược : Asendin
  • Công ty :
    Sản phẩm biệt dược : Asendis
  • Công ty : Eisai
    Sản phẩm biệt dược : Défanyl
  • Công ty : Wyeth
    Sản phẩm biệt dược : Demolox
  • Công ty : Psyco Remedies
    Sản phẩm biệt dược : Oxamine
  • Công ty :
    Sản phẩm biệt dược : Oxcap
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00543
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=2170
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46509117
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00228
ChemSpider
http://www.chemspider.com/Chemical-Structure.2085.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=22870
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0591-5713-01
PharmGKB
http://www.pharmgkb.org/drug/PA448405
Wikipedia
http://en.wikipedia.org/wiki/Amoxapine
RxList
http://www.rxlist.com/cgi/generic/amoxapine.htm
Drugs.com
http://www.drugs.com/cdi/amoxapine.html
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