Tìm theo
Sibutramine
Các tên gọi khác (3) :
  • Butramin
  • Sibutramina
  • Sibutraminum
Thực phẩm chức năng
Thuốc Gốc
Small Molecule
CAS: 106650-56-0
ATC: A08AA10
ĐG : Abbott Laboratories Ltd. , http://www.abbott.com
CTHH: C17H26ClN
PTK: 279.848
Sibutramine (trade name Meridia in the USA, Reductil in Europe and other countries), usually as sibutramide hydrochloride monohydrate, is an orally administered agent for the treatment of obesity. It is a centrally acting stimulant chemically related to amphetamines. Sibutramine is classified as a Schedule IV controlled substance in the United States. In October 2010, Sibutramine was withdrawn from Canadian and U.S. markets due to concerns that the drug increases the risk of heart attack and stroke in patients with a history of heart disease.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C17H26ClN
Phân tử khối
279.848
Monoisotopic mass
279.175377544
InChI
InChI=1S/C17H26ClN/c1-13(2)12-16(19(3)4)17(10-5-11-17)14-6-8-15(18)9-7-14/h6-9,13,16H,5,10-12H2,1-4H3
InChI Key
InChIKey=UNAANXDKBXWMLN-UHFFFAOYSA-N
IUPAC Name
{1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutyl}dimethylamine
Traditional IUPAC Name
sibutramine
SMILES
CC(C)CC(N(C)C)C1(CCC1)C1=CC=C(Cl)C=C1
Độ tan chảy
191-192 °C
Độ hòa tan
2.9 mg/mL (in pH 5.2 water)
logP
5.2
logS
-5.5
pKa (Strongest Basic)
9.77
PSA
3.24 Å2
Refractivity
83.92 m3·mol-1
Polarizability
32.9 Å3
Rotatable Bond Count
5
H Bond Acceptor Count
1
H Bond Donor Count
0
Physiological Charge
1
Number of Rings
2
Bioavailability
1
Ghose Filter
true
Dược Lực Học : Sibutramine is an orally administered agent for the treatment of obesity. Sibutramine exerts its pharmacological actions predominantly via its secondary (M1) and primary (M2) amine metabolites. The parent compound, sibutramine, is a potent inhibitor of serotonin and norepinephrine reuptake in vivo, but not in vitro. However, metabolites M1 and M2 inhibit the reuptake of these neurotransmitters both in vitro and in vivo. In human brain tissue, M1 and M2 also inhibit dopamine reuptake in vitro, but with ~3-fold lower potency than for the reuptake inhibition of serotonin or norepinephrine. Sibutramine, M1 and M2 exhibit no evidence of anticholinergic or antihistaminergic actions. In addition, receptor binding profiles show that sibutramine, M1 and M2 have low affinity for serotonin (5-HT1, 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C), norepinephrine (b, b1, b3, a1 and a2), dopamine (D1 and D2), benzodiazepine, and glutamate (NMDA) receptors. These compounds also lack monoamine oxidase inhibitory activity in vitro and in vivo.
Cơ Chế Tác Dụng : Sibutramine (trade name Meridia in the USA, Reductil in Europe and other countries), usually as sibutramide hydrochloride monohydrate, is an orally administered agent for the treatment of obesity. It is a centrally acting stimulant chemically related to amphetamines. Sibutramine is classified as a Schedule IV controlled substance in the United States. In October 2010, Sibutramine was withdrawn from Canadian and U.S. markets due to concerns that the drug increases the risk of heart attack and stroke in patients with a history of heart disease. Sibutramine produces its therapeutic effects by inhibition of norepinephrine (NE), serotonin (5-hydroxytryptamine, 5-HT), and to a lesser extent, dopamine reuptake at the neuronal synapse. By inhibiting the reuptake of these neurotransmitters, sibutramine promotes a sense of satiety and decrease in appetite, thereby reducing food intake. Data from animal studies also suggest that sibutramine may also increase energy expenditure through thermogenic effects in both the basal and fed states, but this has not been confirmed in humans. Sibutramine and its major pharmacologically active metabolites (M1 and M2) do not act via release of monoamines.
Dược Động Học :
▧ Absorption :
Rapid absorption following oral administration. Absolute bioavailability is not known, but at least 77% of a single oral dose of sibutramine is absorbed.
▧ Protein binding :
97% (to human plasma proteins)
▧ Metabolism :
Hepatic
▧ Route of Elimination :
Sibutramine is metabolized in the liver principally by the cytochrome P450 (3A4) isoenzyme, to desmethyl metabolites, M1 and M2. These active metabolites are further metabolized by hydroxylation and conjugation to pharmacologically inactive metabolites, M5 and M6. Approximately 85% (range 68-95%) of a single orally administered radiolabeled dose was excreted in urine and feces over a 15-day collection period with the majority of the dose (77%) excreted in the urine. The primary route of excretion for M1 and M2 is hepatic metabolism and for M5 and M6 is renal excretion.
▧ Half Life :
1.1 hours
▧ Clearance :
* Oral cl=1750 L/h [oral administration]
Độc Tính : Side effects include dry mouth, anorexia, insomnia, constipation and headache.
Chỉ Định : For the treatment of obesity.
Tương Tác Thuốc :
  • Almotriptan Increased risk of CNS adverse effects
  • Amitriptyline Increased risk of CNS adverse effects
  • Amoxapine Increased risk of CNS adverse effects
  • Citalopram Risk of serotoninergic syndrome
  • Clomipramine Increased risk of CNS adverse effects
  • Cyclosporine Sibutramine increases the effect and toxicity of cyclosporine
  • Desipramine Increased risk of CNS adverse effects
  • Desvenlafaxine Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
  • Dextromethorphan Combination associated with possible serotoninergic syndrome
  • Dihydroergotamine Possible serotoninergic syndrome with this combination
  • Doxepin Increased risk of CNS adverse effects
  • Ergotamine Possible serotoninergic syndrome with this combination
  • Erythromycin Erythromycin increases the effect and toxicity of sibutramine
  • Escitalopram Risk of serotoninergic syndrome
  • Fluoxetine Risk of serotoninergic syndrome
  • Fluvoxamine Risk of serotoninergic syndrome
  • Frovatriptan Increased risk of CNS adverse effects
  • Imipramine Increased risk of CNS adverse effects
  • Isocarboxazid Possible serotoninergic syndrome with this combination
  • Ketoconazole Ketoconazole increases the levels and toxicity of sibutramine
  • Lithium Possible serotoninergic syndrome with this combination
  • Methysergide Possible serotoninergic syndrome
  • Moclobemide Possible serotoninergic syndrome with this combination
  • Naratriptan Increased risk of CNS adverse effects
  • Nefazodone Risk of serotoninergic syndrome
  • Nortriptyline Increased risk of CNS adverse effects
  • Paroxetine Risk of serotoninergic syndrome
  • Pethidine Possible serotoninergic syndrome
  • Phenelzine Possible serotoninergic syndrome with this combination
  • Rasagiline Possible serotoninergic syndrome with this combination
  • Telithromycin Telithromycin may reduce clearance of Sibutramine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Sibutramine if Telithromycin is initiated, discontinued or dose changed.
  • Tramadol Sibutramine may incrase the serotonergic effect of the Tramadol. Concomitant therapy should be avoided.
  • Tranylcypromine Increased risk of serotonin syndrome. Avoid concomitant therapy.
  • Trazodone Increased risk of serotonin syndrome. Avoid concomitant therapy.
  • Trimipramine Increased risk of serotonin syndrome. Concomitant therapy is contraindicated.
  • Venlafaxine Increased risk of serotonin syndrome. Concurrent therapy should be avoided.
  • Vilazodone Sibutramine may enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Avoid combination.
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of sibutramine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of sibutramine if voriconazole is initiated, discontinued or dose changed.
  • Zolmitriptan Use of sibutramine, which inhibits serotonin reuptake, and zolmitriptan, a serotonin 5-HT1D receptor agonist, may cause serotonin syndrome. Concomitant therapy is contraindicated.
Liều Lượng & Cách Dùng : Capsule - Oral
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Meridia 5 mg capsule
    Giá bán buôn : USD >4.0
    Đơn vị tính : capsule
  • Biệt dược thương mại : Meridia 10 mg capsule
    Giá bán buôn : USD >4.02
    Đơn vị tính : capsule
  • Biệt dược thương mại : Meridia 15 mg capsule
    Giá bán buôn : USD >5.11
    Đơn vị tính : capsule
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Butramin
  • Công ty :
    Sản phẩm biệt dược : Medaria
  • Sản phẩm biệt dược : Meridia
  • Công ty :
    Sản phẩm biệt dược : Reductil
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01105
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=5210
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46507740
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07247
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D08513
ChemSpider
http://www.chemspider.com/Chemical-Structure.5021.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0074-2456-12
PharmGKB
http://www.pharmgkb.org/drug/PA451344
Wikipedia
http://en.wikipedia.org/wiki/Sibutramine
RxList
http://www.rxlist.com/cgi/generic/sibutramine.htm
PDRhealth
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/mer1254.shtml
Drugs.com
http://www.drugs.com/cdi/sibutramine.html
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