Tìm theo
Clozapine
Các tên gọi khác (4 ) :
  • Clozapin
  • Clozapina
  • Clozapine
  • Clozapinum
Thuốc điều trị về tâm thần
Thuốc Gốc
Small Molecule
CAS: 5786-21-0
ATC: N05AH02
ĐG : Alamo Pharmaceuticals LLC
CTHH: C18H19ClN4
PTK: 326.823
A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. [PubChem]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C18H19ClN4
Phân tử khối
326.823
Monoisotopic mass
326.129824335
InChI
InChI=1S/C18H19ClN4/c1-22-8-10-23(11-9-22)18-14-4-2-3-5-15(14)20-16-7-6-13(19)12-17(16)21-18/h2-7,12,20H,8-11H2,1H3
InChI Key
InChIKey=QZUDBNBUXVUHMW-UHFFFAOYSA-N
IUPAC Name
6-chloro-10-(4-methylpiperazin-1-yl)-2,9-diazatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,9,12,14-heptaene
Traditional IUPAC Name
6-chloro-10-(4-methylpiperazin-1-yl)-2,9-diazatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,9,12,14-heptaene
SMILES
CN1CCN(CC1)C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12
Độ tan chảy
183-184 °C
Độ hòa tan
11.8 mg/L
logP
3.23
logS
-3.2
pKa (strongest acidic)
15.9
pKa (Strongest Basic)
7.35
PSA
30.87 Å2
Refractivity
97.36 m3·mol-1
Polarizability
35.77 Å3
Rotatable Bond Count
0
H Bond Acceptor Count
4
H Bond Donor Count
1
Physiological Charge
1
Number of Rings
4
Bioavailability
1
Rule of Five
true
Ghose Filter
true
pKa
7.5
Dược Lực Học : Clozapine is a psychotropic agent belonging to the chemical class of benzisoxazole derivatives and is indicated for the treatment of schizophrenia. Clozapine is a selective monoaminergic antagonist with high affinity for the serotonin Type 2 (5HT2), dopamine Type 2 (D2), 1 and 2 adrenergic, and H1 histaminergic receptors. Clozapine acts as an antagonist at other receptors, but with lower potency. Antagonism at receptors other than dopamine and 5HT2 with similar receptor affinities may explain some of the other therapeutic and side effects of Clozapine. Clozapine's antagonism of muscarinic M1-5 receptors may explain its anticholinergic effects. Clozapine's antagonism of histamine H1 receptors may explain the somnolence observed with this drug. Clozapine's antagonism of adrenergic a1 receptors may explain the orthostatic hypotension observed with this drug.
Cơ Chế Tác Dụng : A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. [PubChem] Clozapine's antipsychotic action is likely mediated through a combination of antogistic effects at D2 receptors in the mesolimbic pathway and 5-HT2A receptors in the frontal cortex. D2 antagonism relieves positive symptoms while 5-HT2A antagonism alleviates negative symptoms.
Dược Động Học :
▧ Absorption :
Rapid and almost complete
▧ Protein binding :
97% (bound to serum proteins)
▧ Metabolism :
Hepatic
▧ Route of Elimination :
Approximately 50% of the administered dose is excreted in the urine and 30% in the feces.
▧ Half Life :
8 hours (range 4-12 hours)
Độc Tính : Clozapine carries a black-box warning for agranulocytosis.
Chỉ Định : For use in patients with treatment-resistant schizophrenia.
Tương Tác Thuốc :
  • ado-trastuzumab emtansine Avoid combination due to the increased potential for agranulocytosis.
  • Aflibercept Avoid combination with systemic aflibercept due to enhanced adverse effects of clozapine, including the risk of agranulocytosis
  • Aldesleukin Avoid combination due to enhanced adverse effects of clozapine, especially the risk of agranulocytosis.
  • Alprazolam Increased risk of toxicity
  • Bevacizumab Avoid combination due to increased adverse effects of clozapine, especially the risk of agranulocytosis.
  • Bromazepam Bromazepam may increase the adverse effects of clozapine. Consider alternate therapy or a reduction in the bromazepam dose. Monitor for respiratory depression and hypotension if concomitant therapy is initiated.
  • Caffeine Caffeine increases the effect and toxicity of clozapine
  • Carbamazepine Carbamazepine may decrease the serum concentration of clozapine by increasing its metabolism. Concomitant therapy should also be avoided due to increased risk of bone marrow suppression. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of clozapine if carbamazepine is initiated, discontinued or dose changed.
  • Chlordiazepoxide Increased risk of toxicity
  • Cimetidine Cimetidine may increase the serum concentratin of clozapine. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of clozapine if cimetidine is initiated, discontinued or dose changed.
  • Cinolazepam Increased risk of toxicity
  • Ciprofloxacin Ciprofloxacin may increase clozapine serum levels
  • Citalopram The antidepressant increases the effect of clozapine
  • Clobazam Increased risk of toxicity
  • Clonazepam Increased risk of toxicity
  • Clorazepate Increased risk of toxicity
  • Diazepam Increased risk of toxicity
  • Dihydrocodeine CNS depressants may enhance the adverse effects and toxicity of other CNS depressants. It is recommended to monitor therapy.
  • Donepezil Possible antagonism of action
  • Erythromycin Erythromycin increases the effect of clozapine
  • Estazolam Increased risk of toxicity
  • Ethotoin Hydantoin decreases the effect of clozapine
  • Flunitrazepam Increased risk of toxicity
  • Fluoxetine The antidepressant increases the effect of clozapine
  • Flurazepam Increased risk of toxicity
  • Fluvoxamine The antidepressant increases the effect of clozapine
  • Fosphenytoin Hydantoin decreases the effect of clozapine
  • Galantamine Possible antagonism of action
  • Gemtuzumab ozogamicin Avoid combination due to adverse effects of clozapine including the risk of agranulocytosis.
  • Halazepam Increased risk of toxicity
  • Haloperidol Clozapine, a moderate CYP2D6 inhibitor, may increase the serum concentration of haloperidol by decreasing its metabolism. Additive CNS despresant and anticholinergic effects may also occur. Monitor for changes in the therapeutic and adverse effects of haloperidol if clozapine is initiated, discontinued or dose changed. Also monitor for increased CNS depressant and anticholinergic effects during concomitant therapy.
  • Ibritumomab Avoid combination due to enhanced adverse effects of clozapine, including agranulocytosis.
  • Josamycin Erythromycin increases the effect of clozapine
  • Ketazolam Increased risk of toxicity
  • Lamotrigine Lamotrigine increases the effect and toxicity of clozapine
  • Lorazepam Increased risk of toxicity
  • Mephenytoin Hydantoin decreases the effect of clozapine
  • Midazolam Increased risk of toxicity
  • Modafinil Modafinil increases the effect and toxicity of clozapine
  • Nitrazepam Increased risk of toxicity
  • Norfloxacin Ciprofloxacin may increase clozapine serum levels
  • Obinutuzumab Risk of agranulocytosis may be increased due to enhanced adverse effects of clozapine by myelosuppressive agents. It is recommanded that combination may be avoided.
  • Oxazepam Increased risk of toxicity
  • Paclitaxel Avoid combination due to the potential enhancement of agranulocytosis by clozapine.
  • Phenytoin Phenytoin may decrease the effect of clozapine.
  • Prazepam Increased risk of toxicity
  • Quazepam Increased risk of toxicity
  • Rifabutin Rifabutin decreases the effect of clozapine
  • Rifampicin Rifampin decreases the effect of clozapine
  • Ritonavir Ritonavir increases the effect and toxicity of clozapine
  • Rivastigmine Possible antagonism of action
  • Sertraline The antidepressant increases the effect of clozapine
  • Tacrine The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Clozapine, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
  • Tamoxifen Clozapine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
  • Tamsulosin Clozapine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Clozapine is initiated, discontinued, or dose changed.
  • Temazepam The benzodiazepine, Temazepam, may increase the adverse effects of Clozapine. Monitor for respiratory depression and hypotension if concomitant therapy is initiated.
  • Tetrabenazine 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.
  • Thiabendazole The strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Clozapine by decreasing Clozapine metabolism and clearance. Monitor for changes in the therapeutic and adverse effects of Clozapine if Thiabendazole is initiated, discontinued or dose changed.
  • Tofacitinib Avoid combination due to the increased risk of clozapine induced agranulocytosis.
  • Tramadol Clozapine may decrease the effect of Tramadol by decreasing active metabolite production.
  • Triazolam Increased risk of toxicity
  • Trimethobenzamide Trimethobenzamide and Clozapine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
  • Triprolidine Triprolidine and Clozapine, 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 Clozapine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
  • Vilazodone Selective Serotonin Reuptake Inhibitors may decrease the metabolism of clozapine. If concurrent use of these agents is employed, monitor for increased toxic effects of clozapine if a selective serotonin reuptake inhibitor (SSRI) is initiated/dose increased, or decreased effects if a SSRI is discontinued/dose decreased.
Liều Lượng & Cách Dùng : Tablet - Oral
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Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00363
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=2818
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46506474
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C06924
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00283
ChemSpider
http://www.chemspider.com/Chemical-Structure.2716.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=22869
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/57664-345-88
PharmGKB
http://www.pharmgkb.org/drug/PA449061
Wikipedia
http://en.wikipedia.org/wiki/Clozapine
RxList
http://www.rxlist.com/cgi/generic3/clozapine.htm
PDRhealth
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/clo1089.shtml
Drugs.com
http://www.drugs.com/clozapine.html
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