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药品详细

Clonazepam(氯硝西泮)

化学结构式图
中文名
氯硝西泮
英文名
Clonazepam
分子式
C15H10ClN3O3
化学名
5-(2-chlorophenyl)-7-nitro-2,3-dihydro-1H-1,4-benzodiazepin-2-one
分子量
Average: 315.711
Monoisotopic: 315.041068908
CAS号
1622-61-3
ATC分类
N03A 未知
药物类型
small molecule
阶段
illicit, approved
商品名
同义名
基本介绍

An anticonvulsant used for several types of seizures, including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures, although tolerance may develop. It is seldom effective in generalized tonic-clonic or partial seizures. The mechanism of action appears to involve the enhancement of gamma-aminobutyric acid receptor responses. [PubChem]

生产厂家
  • Actavis elizabeth llc
  • Alphapharm party ltd
  • Apotex inc
  • Barr laboratories inc
  • Caraco pharmaceutical laboratories ltd
  • Hoffmann la roche inc
  • Mylan pharmaceuticals inc
  • Par pharmaceutical inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Vintage pharmaceuticals inc
  • Watson laboratories inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Dreifuss FE, Penry JK, Rose SW, Kupferberg HJ, Dyken P, Sato S: Serum clonazepam concentrations in children with absence seizures. Neurology. 1975 Mar;25(3):255-8. Pubmed
  2. Robertson MD, Drummer OH: Postmortem drug metabolism by bacteria. J Forensic Sci. 1995 May;40(3):382-6. Pubmed
  3. Rosen GM, Turner MJ 3rd: Synthesis of spin traps specific for hydroxyl radical. J Med Chem. 1988 Feb;31(2):428-32. Pubmed
  4. Rosen GM, Demos HA, Rauckman EJ: Not all aromatic nitro compounds form free radicals. Toxicol Lett. 1984 Aug;22(2):145-52. Pubmed
  5. Earley JV, Fryer RI, Ning RY: Quinazolines and 1,4-benzodiazepines. LXXXIX: Haptens useful in benzodiazepine immunoassay development. J Pharm Sci. 1979 Jul;68(7):845-50. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Benzodiazepines
  • Lactams
Substructures
  • Benzodiazepines
  • Nitrobenzenes
  • Oxoazaniums
  • Amino Ketones
  • Benzene and Derivatives
  • Aryl Halides
  • Carboxylic Acids and Derivatives
  • Halobenzenes
  • Nitro compounds
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Diazepines
  • Lactams
  • Imines
  • Anilines
适应症
药理
Indication Clonazepam is used as an anticonvulsant in the treatment of the Lennox-Gastaut syndrome (petit mal variant), akinetic and myoclonic seizures. It can also be used for the treatment of panic disorders.
Pharmacodynamics Clonazepam, a benzodiazepine, is used primarily as an anticonvulsant in the treatment of absence seizures, petit mal variant seizures (Lennox-Gastaut syndrome), akinetic and myoclonic seizures, and nocturnal myoclonus. It enhances the activity of gamma aminobutyric acid (GABA), which is a major inhibitory neurotransmitter in the central nervous system. In animals, convulsions are antagonized occurs following administration of clonazepam. In humans, clonazepam suppresses the spike and wave discharge in absence seizures (petit mal) and decreases the frequency, amplitude, duration, and spread of discharge in minor motor seizures.
Mechanism of action Allosteric interactions between central benzodiazepine receptors and gamma-aminobutyric acid (GABA) receptors potentiate the effects of GABA. As GABA is an inhibitory neurotransmitter, this results in increased inhibition of the ascending reticular activating system. Benzodiazepines, in this way, block the cortical and limbic arousal that occurs following stimulation of the reticular pathways.
Absorption Clonazepam is rapidly and completely absorbed after oral administration. The absolute bioavailability of clonazepam is about 90%. Cmax, oral administration = 1 -4 hours.
Volume of distribution Not Available
Protein binding 85% bound to plasma proteins.
Metabolism
Hepatic (cytochrome P450, including CYP3A). Biotransformation occurs mainly by reduction of the 7-nitro group to the 4-amino derivative. This derivative can be acetylated, hydroxylated, and glucuronidated.
Route of elimination Clonazepam is highly metabolized, with less than 2% unchanged clonazepam being excreted in the urine. Metabolites of Klonopin are excreted by the kidneys. Clonazepam also undergoes acetylation via NAT2.
Half life 30-40 hours
Clearance Not Available
Toxicity Somnolence, confusion, coma, and diminished reflexes. The most commonly reported adverse event when clonazepam is used for seizure disorders is CNS depression. LD50, oral, rats = >15000 mg/kg.
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 236.5 - 238.5 °C MSDS
water solubility 100 mg/L (at 25 °C) MERCK INDEX (1996)
logP 2.41 HANSCH,C ET AL. (1995)
Predicted Properties
Property Value Source
water solubility 1.06e-02 g/l ALOGPS
logP 2.76 ALOGPS
logP 3.15 ChemAxon
logS -4.5 ALOGPS
pKa (strongest acidic) 11.89 ChemAxon
pKa (strongest basic) 1.86 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 87.28 ChemAxon
rotatable bond count 2 ChemAxon
refractivity 84.02 ChemAxon
polarizability 29.59 ChemAxon
药物相互作用
Drug Interaction
Cimetidine Cimetidine may increase the effect of the benzodiazepine, clonazepam.
Clozapine Increased risk of toxicity
Fluconazole Fluconazole may increase the effect of the benzodiazepine, clonazepam.
Indinavir The protease inhibitor, indinavir, may increase the effect of the benzodiazepine, clonazepam.
Itraconazole Itraconazole may increase the effect of the benzodiazepine, clonazepam.
Kava Kava may increase the effect of the benzodiazepine, clonazepam.
Ketoconazole Ketoconazole may increase the effect of the benzodiazepine, clonazepam.
Nelfinavir The protease inhibitor, nelfinavir, may increase the effect of the benzodiazepine, clonazepam.
Omeprazole Omeprazole may increase the effect of the benzodiazepine, clonazepam.
Ritonavir The protease inhibitor, ritonavir, may increase the effect of the benzodiazepine, clonazepam.
Saquinavir The protease inhibitor, saquinavir, may increase the effect of the benzodiazepine, clonazepam.
St. John's Wort St. John's Wort may decrease the effect of the benzodiazepine, clonazepam.
Telithromycin Telithromycin may reduce clearance of Clonazepam. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Clonazepam if Telithromycin is initiated, discontinued or dose changed.
Tipranavir Tipranavir may decrease the metabolism and clearance of Clonazepam. Consider alternate therapy or monitor for Clonazepam toxic effects if Tipranavir is initiated or dose increased.
Triprolidine The CNS depressants, Triprolidine and Clonazepam, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Vigabatrin Vigabatrin increases Cmax of clonazepam by 30% and decreases Tmax by 45%
Voriconazole Voriconazole may increase the serum concentration of clonazepam by decreasing its metabolism. Monitor for clonazepam toxicity if voriconazole is initiated or dose increased.
食物相互作用
  • Avoid alcohol.
  • Avoid excessive quantities of coffee or tea (Caffeine).
  • Take without regard to meals.

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