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药品详细

Zopiclone(佐匹克隆)

化学结构式图
中文名
佐匹克隆
英文名
Zopiclone
分子式
C17H17ClN6O3
化学名
6-(5-chloropyridin-2-yl)-7-oxo-5H,6H,7H-pyrrolo[3,4-b]pyrazin-5-yl 4-methylpiperazine-1-carboxylate
分子量
Average: 388.808
Monoisotopic: 388.105066147
CAS号
43200-80-2
ATC分类
N05C 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Zopiclone is a novel hypnotic agent used in the treatment of insomnia. Its mechanism of action is based on modulating benzodiazepine receptors. In addition to zopiclone’s benzodiazepine pharmacological properties it also has some barbiturate like properties.

生产厂家
    封装厂家
    参考
    Synthesis Reference Not Available
    General Reference
    1. Liu HJ, Sato K, Shih HC, Shibuya T, Kawamoto H, Kitagawa H: Pharmacologic studies of the central action of zopiclone: effects on locomotor activity and brain monoamines in rats. Int J Clin Pharmacol Ther Toxicol. 1985 Mar;23(3):121-8. Pubmed
    2. Sato K, Hong YL, Yang MS, Shibuya T, Kawamoto H, Kitagawa H: Pharmacologic studies of central actions of zopiclone: influence on brain monoamines in rats under stressful condition. Int J Clin Pharmacol Ther Toxicol. 1985 Apr;23(4):204-10. Pubmed
    3. Dundar Y, Dodd S, Strobl J, Boland A, Dickson R, Walley T: Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis. Hum Psychopharmacol. 2004 Jul;19(5):305-22. Pubmed
    4. Blanchard JC, Julou L: Suriclone: a new cyclopyrrolone derivative recognizing receptors labeled by benzodiazepines in rat hippocampus and cerebellum. J Neurochem. 1983 Mar;40(3):601-7. Pubmed
    5. Julou L, Bardone MC, Blanchard JC, Garret C, Stutzmann JM: Pharmacological studies on zopiclone. Pharmacology. 1983;27 Suppl 2:46-58. Pubmed
    剂型
    规格
    化合物类型
    Type small molecule
    Classes
    • Lactams
    • Cyclopyrrolones
    Substructures
    • Carbamates and Derivatives
    • Amino Ketones
    • Pyridines and Derivatives
    • Piperazines
    • Ethers
    • Aliphatic and Aryl Amines
    • Aryl Halides
    • Aminopyridines and Derivatives
    • Pyrazines
    • Heterocyclic compounds
    • Aromatic compounds
    • Carboxamides and Derivatives
    • Lactams
    • Imines
    • Cyclopyrrolones
    • Pyrrolines
    适应症
    药理
    Indication For the short-term treatment of insomnia.
    Pharmacodynamics Zopiclone is a nonbenzodiazepine hypnotic from the pyrazolopyrimidine class and is indicated for the short-term treatment of insomnia. While Zopiclone is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties, it interacts with the gamma-aminobutyric acid-benzodiazepine (GABABZ) receptor complex. Subunit modulation of the GABABZ receptor chloride channel macromolecular complex is hypothesized to be responsible for some of the pharmacological properties of benzodiazepines, which include sedative, anxiolytic, muscle relaxant, and anticonvulsive effects in animal models. Zopiclone binds selectively to the brain alpha subunit of the GABA A omega-1 receptor.
    Mechanism of action Zopiclone exerts its action by binding on the benzodiazepine receptor complex and modulation of the GABABZ receptor chloride channel macromolecular complex. Both zopiclone and benzodiazepines act indiscriminately at the benzodiazepine binding site on α1, α2, α3 and α5 GABAA containing receptors as full agonists causing an enhancement of the inhibitory actions of GABA to produce the therapeutic (hypnotic and anxiolytic) and adverse effects of zopiclone.
    Absorption Rapidly absorbed following oral administration.
    Volume of distribution Not Available
    Protein binding Approximately 45%
    Metabolism
    Extensively metabolized in the liver via decarboxylation (major pathway), demethylation, and side chain oxidation. Metabolites include an N-oxide derivative (weakly active; approximately 12% of a dose) and an N-desmethyl metabolite (inactive; approximately 16%). Approximately 50% of a dose is converted to other inactive metabolites via decarboxylation. Hepatic microsomal enzymes are apparently not involved in zopiclone clearance.

    Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

    Substrate Enzymes Product
    Zopiclone
    		Zopiclone N-oxide Details
    Zopiclone
    		N-Desmethylzopiclone Details
    Zopiclone
    		CO2 Details
    Zopiclone
    		zopiclone-N-oxide Details
    Zopiclone
    		N-desmethylzopiclone Details
    Route of elimination Not Available
    Half life Elimination half life is approximately 5 hours (range 3.8 to 6.5 hours) and is prolonged to 11.9 hours in patients with hepatic insufficiency.
    Clearance Not Available
    Toxicity Rare individual instances of fatal outcomes following overdose with racemic zopiclone have been reported in European postmarketing reports, most often associated with overdose with other CNS-depressant agent. Signs and symptoms of overdose effects of CNS depressants can be expected to present as exaggerations of the pharmacological effects noted in preclinical testing.
    Affected organisms
    • Humans and other mammals
    Pathways Not Available
    理化性质
    Properties
    State solid
    Experimental Properties
    Property Value Source
    melting point 178 °C PhysProp
    water solubility 0.151 mg/mL at 25 °C MEYLAN,WM et al. (1996)
    logP 0.8 Not Available
    Predicted Properties
    Property Value Source
    water solubility 8.85e-01 g/l ALOGPS
    logP 0.97 ALOGPS
    logP 0.81 ChemAxon
    logS -2.6 ALOGPS
    pKa (strongest acidic) 13.04 ChemAxon
    pKa (strongest basic) 6.89 ChemAxon
    physiological charge 0 ChemAxon
    hydrogen acceptor count 6 ChemAxon
    hydrogen donor count 0 ChemAxon
    polar surface area 91.76 ChemAxon
    rotatable bond count 3 ChemAxon
    refractivity 95.89 ChemAxon
    polarizability 37.67 ChemAxon
    药物相互作用
    Drug Interaction
    Amprenavir Amprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if amprenavir is initiated, discontinued or dose changed.
    Atazanavir Atazanavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if atazanavir is initiated, discontinued or dose changed.
    Clarithromycin Clarithromycin, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if clarithromycin is initiated, discontinued or dose changed.
    Conivaptan Conivaptan, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if conivaptan is initiated, discontinued or dose changed.
    Darunavir Darunavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if darunavir is initiated, discontinued or dose changed.
    Delavirdine Delavirdine, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if delavirdine is initiated, discontinued or dose changed.
    Erythromycin The macrolide antibiotic, erythromycin, may increase the serum concentration of zopiclone. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if erythromycin is initiated, discontinued or dose changed.
    Fosamprenavir Fosamprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if fosamprenavir is initiated, discontinued or dose changed.
    Imatinib Imatinib, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if imatinib is initiated, discontinued or dose changed.
    Indinavir Indinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if indinavir is initiated, discontinued or dose changed.
    Isoniazid Isoniazid, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if isoniazid is initiated, discontinued or dose changed.
    Itraconazole Itraconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if itraconzole is initiated, discontinued or dose changed.
    Ketoconazole Ketonconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if ketoconazole is initiated, discontinued or dose changed.
    Lopinavir Lopinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if lopinavir is initiated, discontinued or dose changed.
    Methotrimeprazine Additive CNS depressant effects. Reduce zopiclone dose by half upon initiation of methotrimeprazine. Zopiclone dose may be adjusted once methotrimeprazine dose has been established. Monitor for increased CNS depression.
    Nefazodone Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if nefazodone is initiated, discontinued or dose changed.
    Nelfinavir Nelfinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if nelfinavir is initiated, discontinued or dose changed.
    Nicardipine Nicardipine, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if nicardipine is initiated, discontinued or dose changed.
    Posaconazole Posaconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if posaconazole is initiated, discontinued or dose changed.
    Quinidine Quinidine, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if quinidine is initiated, discontinued or dose changed.
    Ritonavir Ritonavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if ritonavir is initiated, discontinued or dose changed.
    Saquinavir Saquinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if saquinavir is initiated, discontinued or dose changed.
    Telithromycin Telithromycin, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if telithromycin is initiated, discontinued or dose changed.
    Tolbutamide Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Zopiclone. Consider alternate therapy or monitor for changes in Zopiclone therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
    Triprolidine The CNS depressants, Triprolidine and Zopiclone, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
    Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if voriconazole is initiated, discontinued or dose changed.
    食物相互作用
    Not Available

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