Tìm theo
Tetrabenazine
Các tên gọi khác (9 ) :
  • 1,2,4,6,7,11b-hexahydro-3-Isobutyl-9,10-dimethoxy-2H-benzo[a]quinolizin-2-one
  • 2-oxo-3-Isobutyl-9,10-dimethoxy-1,2,3,4,6,7-hexahydro-11bh-benzo[a]quinolizine
  • 2-oxo-3-Isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-benzoquinolizine
  • TBZ
  • Tetra benazin
  • Tetrabenazina
  • Tetrabenazinum
  • Tetrabenzaine
  • Tetrabenzine
adrenergic uptake inhibitors
Thuốc Gốc
Small Molecule
CAS: 58-46-8
ATC: N07XX06
ĐG : Laboratories Fournier Sca
CTHH: C19H27NO3
PTK: 317.4226
A drug formerly used as an antipsychotic but now used primarily in the symptomatic treatment of various hyperkinetic disorders. It is a monoamine depletor and used as symptomatic treatment of chorea associated with Huntington's disease. FDA approved on August 15, 2008.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C19H27NO3
Phân tử khối
317.4226
Monoisotopic mass
317.199093735
InChI
InChI=1S/C19H27NO3/c1-12(2)7-14-11-20-6-5-13-8-18(22-3)19(23-4)9-15(13)16(20)10-17(14)21/h8-9,12,14,16H,5-7,10-11H2,1-4H3
InChI Key
InChIKey=MKJIEFSOBYUXJB-UHFFFAOYSA-N
IUPAC Name
9,10-dimethoxy-3-(2-methylpropyl)-1H,2H,3H,4H,6H,7H,11bH-pyrido[2,1-a]isoquinolin-2-one
Traditional IUPAC Name
tetrabenazine
SMILES
COC1=C(OC)C=C2C3CC(=O)C(CC(C)C)CN3CCC2=C1
Độ tan chảy
126 °C
Độ hòa tan
Sparingly soluble
logP
3.4
logS
-2.9
pKa (strongest acidic)
18.24
pKa (Strongest Basic)
7.41
PSA
38.77 Å2
Refractivity
91.31 m3·mol-1
Polarizability
36.59 Å3
Rotatable Bond Count
4
H Bond Acceptor Count
4
H Bond Donor Count
0
Physiological Charge
1
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
pKa
6.51
Dược Lực Học : Prolongation of the QTc interval has been observed at doses of 50 mg. In rats, it has been observed that tetrabenazine or its metabolites bind to melanin-containing tissues such as the eyes and skin. After a single oral dose of radiolabeled tetrabenazine, radioactivity was still detected in eye and fur at 21 days post dosing.
Cơ Chế Tác Dụng : A drug formerly used as an antipsychotic but now used primarily in the symptomatic treatment of various hyperkinetic disorders. It is a monoamine depletor and used as symptomatic treatment of chorea associated with Huntington's disease. FDA approved on August 15, 2008. Tetrabenazine is a reversible human vesicular monoamine transporter type 2 inhibitor (Ki = 100 nM). It acts within the basal ganglia and promotes depletion of monoamine neurotransmitters serotonin, norepinephrine, and dopamine from stores. It also decreases uptake into synaptic vesicles. Dopamine is required for fine motor movement, so the inhibition of its transmission is efficacious for hyperkinetic movement. Tetrabenazine exhibits weak in vitro binding affinity at the dopamine D2 receptor (Ki = 2100 nM).
Dược Động Học :
▧ Absorption :
Following oral administration of tetrabenazine, the extent of absorption is at least 75%. After single oral doses ranging from 12.5 to 50 mg, plasma concentrations of tetrabenazine are generally below the limit of detection because of the rapid and extensive hepatic metabolism of tetrabenazine. Food does not affect the absorption of tetrabenazine. Cmax, oral = 4.8 ng/mL in HD or tardive dyskinesia patients; Tmax, oral = 69 min in HD or tardive dyskinesia patients
▧ Volume of Distribution :
Steady State, IV, in HD or tardive dyskinesia patients: 385L. Tetrabenazine is rapidly distributed to the brain following IV injection. The site with the highest binding is the striatum, while the lowest binding was observed in the cortex.
▧ Protein binding :
Tetrabenazine = 82 - 88%; α-HTBZ = 60 - 68%; β-HTBZ = 59 - 63%.
▧ Metabolism :
Tetrabenazine is hepatically metabolized. Carbonyl reductase in the liver is responsible for the formation of two major active metabolites: α-dihydrotetrabenazine (α-HTBZ) and β-dihydrotetrabenazine (β-HTBZ). α-HTBZ is further metabolized into 9-desmethyl-α-DHTBZ, a minor metabolite by CYP2D6 and with some contribution of CYP1A2. β-HTBZ is metabolized to another major circulating metabolite, 9-desmethyl-β-DHTBZ, by CYP2D6. The Tmax of this metabolite is 2 hours post-administration of tetrabenazine.
▧ Route of Elimination :
After oral administration, tetrabenazine is extensively hepatically metabolized, and the metabolites are primarily renally eliminated (75%). Tetrabenazine is also cleared fecally (7% to 16%). Unchanged tetrabenazine has not been found in human urine. Urinary excretion of α-HTBZ or β-HTBZ (the major metabolites) accounted for less than 10% of the administered dose.
▧ Half Life :
α-HTBZ = 7 hours; β-HTBZ = 5 hours; 9-desmethyl-β-DHTBZ = 12 hours.
▧ Clearance :
IV, 1.67 L/min in HD or tardive dyskinesia patients
Độc Tính : Dose-limiting adverse effects are sedation, parkinsonism, akathsia, and depression. LD50 oral, mouse: 550 mg/kg
Chỉ Định : Treatment of hyperkinetic movement disorders like chorea in Huntington's disease, hemiballismus, senile chorea, Tourette syndrome and other tic disorders, and tardive dyskinesia
Tương Tác Thuốc :
  • Acetophenazine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects. Similar pharmacologic properties thus combination therapy will worsen the severity of sedative, parkinsonian, and extrapyramidal adverse effects.
  • Aripiprazole May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
  • Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Chlorpromazine May cause dopamine deficiency. Similar pharmacologic properties thus combination therapy will worsen the severity of sedative, parkinsonian, and extrapyramidal adverse effects.
  • Clozapine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects. Similar pharmacologic properties thus combination therapy will worsen the severity of sedative, parkinsonian, and extrapyramidal adverse effects.
  • Cocaine CYP2D6 Inhibitors (Strong) such as cocaine may increase the serum concentration of tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Patients receiving a strong inhibitor of CYP2D6 together with tetrabenazine should not exceed 50mg of tetrabenazine. Also, patients already taking tetrabenazine prior to starting a strong CYP2D6 inhibitor should have their tetrabenazine dose reduced by 50% upon initiation of the strong CYP2D6 inhibitor.
  • Droperidol May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects. May cause dopamine deficiency. Similar pharmacologic properties thus combination therapy will worsen the severity of sedative, parkinsonian, and extrapyramidal adverse effects.
  • Fluoxetine Strong CYP2D6 inhibitors may increase exposure of the metabolites of tetrabenazine. Consider a reduction of dose.
  • Flupentixol May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects. Similar pharmacologic properties thus combination therapy will worsen the severity of sedative, parkinsonian, and extrapyramidal adverse effects.
  • Fluphenazine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects. Similar pharmacologic properties thus combination therapy will worsen the severity of sedative, parkinsonian, and extrapyramidal adverse effects.
  • Furazolidone Tetrabenazine may increase the adverse/toxic effects of Furazolidine. Concomitant therapy is contraindicated.
  • Haloperidol May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects. May cause dopamine deficiency. Similar pharmacologic properties thus combination therapy will worsen the severity of sedative, parkinsonian, and extrapyramidal adverse effects.
  • Isocarboxazid Tetrabenazine may increase the adverse/toxic effects of Isocarboxazid. Concomitant therapy is contraindicated.
  • L-DOPA Tetrabenazine may cause Parkinsonian symptoms and neutralize the effect of Levodopa.
  • Linezolid Tetrabenazine may increase the adverse/toxic effects of Linezolid. Concomitant therapy is contraindicated.
  • Lithium Inhibit biochemical and behavioural effects of tetrabenazine. Heed caution when using agents in combination.
  • Loxapine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
  • Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Mesoridazine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
  • Metoclopramide Similar pharmacologic properties thus combination therapy will worsen the severity of sedative, parkinsonian, and extrapyramidal adverse effects.
  • Moclobemide Tetrabenazine may increase the adverse/toxic effects of Moclobemide. Concomitant therapy is contraindicated.
  • Molindone May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
  • Olanzapine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
  • Paliperidone May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects. Similar pharmacologic properties thus combination therapy will worsen the severity of sedative, parkinsonian, and extrapyramidal adverse effects.
  • Paroxetine Paroxetine is a strong CYP2D6 inhibitor thus increasing half life of dihydrotetrabenazine moieties. Dose of tetrabenazine should be reduced
  • Perphenazine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
  • Phenelzine Tetrabenazine may increase the adverse/toxic effects of Phenelzine. Concomitant therapy is contraindicated.
  • Pimozide May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
  • Procarbazine Tetrabenazine may increase the adverse/toxic effects of Procarbazine. Concomitant therapy is contraindicated.
  • Prochlorperazine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
  • Quetiapine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
  • Quinidine Strong CYP2D6 inhibitors may increase exposure of the metabolites of tetrabenazine. Consider a reduction of dose.
  • Rasagiline Tetrabenazine may increase the adverse/toxic effects of Rasagiline. Concomitant therapy is contraindicated.
  • Reserpine Reserpine may increase the adverse/toxic effects of tetrabenazine as they have similar pharmacologic properties. Concomitant therapy is contraindicated.
  • Risperidone May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
  • Selegiline Tetrabenazine may increase the adverse/toxic effects of Selegiline. Concomitant therapy is contraindicated.
  • Tacrolimus May cause additive QTc-prolonging effects. Concomitant therapy should be avoided.
  • Telithromycin Telithromycin may increase the QTc-prolonging effect of Tetrabenazine. Concomitant therapy should be avoided.
  • Terbinafine Terbinafine may reduce the metabolism and clearance of Tetrabenazine. Consider alternate therapy or monitor for therapeutic/adverse effects of Tetrabenazine if Terbinafine is initiated, discontinued or dose changed.
  • Thioridazine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
  • Thiothixene Additive QTc prolongation may occur. QTc prolongation can lead to Torsade de Pointes (TdP). Concomitant therapy should be avoided.
  • Toremifene May cause additive QTc-prolonging effects. Concomitant therapy is contraindicated.
  • Tranylcypromine Tetrabenazine may increase the adverse/toxic effects of Tranylcypromine. Concomitant therapy is contraindicated.
  • Trifluoperazine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
  • Trimipramine May cause additive QTc-prolonging effects. Concomitant therapy should be avoided.
  • Triprolidine The CNS depressants, Triprolidine and Tetrabenazine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
  • Voriconazole Additive QTc prolongation may occur. Concomitant therapy should be avoided.
  • Vorinostat Additive QTc prolongation may occur. Concomitant therapy should be avoided.
  • Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.
  • Zuclopenthixol Additive QTc prolongation may occur. QTc prolongation can lead to Torsade de Pointes (TdP). Concomitant therapy should be avoided.
Liều Lượng & Cách Dùng : Tablet - Oral - 12.5 mg, 25 mg
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Xenazine 12.5 mg tablet
    Giá bán buôn : USD >37.29
    Đơn vị tính : tablet
  • Biệt dược thương mại : Xenazine 25 mg tablet
    Giá bán buôn : USD >74.57
    Đơn vị tính : tablet
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Nitoman
  • Công ty :
    Sản phẩm biệt dược : Rubigen
  • Sản phẩm biệt dược : Xenazine
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB04844
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=6018
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46506426
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C11168
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D08575
ChemSpider
http://www.chemspider.com/Chemical-Structure.5796.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50017701
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/67386-421-01
PharmGKB
http://www.pharmgkb.org/drug/PA140222719
Wikipedia
http://en.wikipedia.org/wiki/Tetrabenazine
RxList
http://www.rxlist.com/xenazine-drug.htm
Drugs.com
http://www.drugs.com/cdi/tetrabenazine.html
... loading
... loading