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药品详细

Naltrexone(纳曲酮)

化学结构式图
中文名
纳曲酮
英文名
Naltrexone
分子式
C20H23NO4
化学名
(1S,5R,13R,17S)-4-(cyclopropylmethyl)-10,17-dihydroxy-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7(18),8,10-trien-14-one
分子量
Average: 341.4009
Monoisotopic: 341.162708229
CAS号
16590-41-3
ATC分类
N07B 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. [PubChem]

生产厂家
  • Actavis totowa llc
  • Alkermes inc
  • Barr laboratories inc
  • Duramed pharmaceuticals inc
  • Mallinckrodt inc
  • Sandoz inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Schmitz JM, Stotts AL, Rhoades HM, Grabowski J: Naltrexone and relapse prevention treatment for cocaine-dependent patients. Addict Behav. 2001 Mar-Apr;26(2):167-80. Pubmed
  2. Krystal JH, Gueorguieva R, Cramer J, Collins J, Rosenheck R: Naltrexone is associated with reduced drinking by alcohol dependent patients receiving antidepressants for mood and anxiety symptoms: results from VA Cooperative Study No. 425, “Naltrexone in the treatment of alcoholism”. Alcohol Clin Exp Res. 2008 Jan;32(1):85-91. Epub 2007 Dec 7. Pubmed
  3. Ray LA, Chin PF, Miotto K: Naltrexone for the treatment of alcoholism: clinical findings, mechanisms of action, and pharmacogenetics. CNS Neurol Disord Drug Targets. 2010 Mar;9(1):13-22. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Morphinans
  • Benzylisoquinolines
Substructures
  • Morphinans
  • Benzofurans
  • Hydroxy Compounds
  • Naphthalenes
  • Phenols and Derivatives
  • Benzylisoquinolines
  • Cyclopropane and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Phenylpiperidines
  • Methoxyphenols
  • Aliphatic and Aryl Amines
  • Alcohols and Polyols
  • Phenanthrenes
  • Catechols
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Phenylpropylamines
  • (Iso)quinolines and Derivatives
  • Cyclohexenes and Derivatives
  • Phenyl Esters
  • Amphetamines
  • Catecholamines and Derivatives
  • Piperidines
  • Ketones
适应症
药理
Indication Used as an adjunct to a medically supervised behaviour modification program in the maintenance of opiate cessation in individuals who were formerly physically dependent on opiates and who have successfully undergone detoxification. Also used for the management of alcohol dependence in conjunction with a behavioural modification program.
Pharmacodynamics Naltrexone, a pure opioid antagonist, is a synthetic congener of oxymorphone with no opioid agonist properties. Naltrexone is indicated in the treatment of alcohol dependence and for the blockade of the effects of exogenously administered opioids. It markedly attenuates or completely blocks, reversibly, the subjective effects of intravenously administered opioids. When co-administered with morphine, on a chronic basis, naltrexone blocks the physical dependence to morphine, heroin and other opioids. In subjects physically dependent on opioids, naltrexone will precipitate withdrawal symptomatology.
Mechanism of action Naltrexone is a pure opiate antagonist and has little or no agonist activity. The mechanism of action of naltrexone in alcoholism is not understood; however, involvement of the endogenous opioid system is suggested by preclinical data. Naltrexone is thought to act as a competitive antagonist at mc, κ, and δ receptors in the CNS, with the highest affintiy for the μ receptor. Naltrexone competitively binds to such receptors and may block the effects of endogenous opioids. This leads to the antagonization of most of the subjective and objective effects of opiates, including respiratory depression, miosis, euphoria, and drug craving. The major metabolite of naltrexone, 6-β-naltrexol, is also an opiate antagonist and may contribute to the antagonistic activity of the drug.
Absorption Although well absorbed orally, naltrexone is subject to significant first pass metabolism with oral bioavailability estimates ranging from 5 to 40%.
Volume of distribution
  • 1350 L [intravenous administration]
Protein binding 21% bound to plasma proteins over the therapeutic dose range.
Metabolism
Hepatic. When administered orally, naltrexone undergoes extensive biotransformation and is metabolized to 6 beta-naltrexol (which may contribute to the therapeutic effect) and other minor metabolites.

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

Substrate Enzymes Product
Naltrexone
    		6-beta-naltrexol Details
    Route of elimination Both parent drug and metabolites are excreted primarily by the kidney (53% to 79% of the dose), however, urinary excretion of unchanged naltrexone accounts for less than 2% of an oral dose and fecal excretion is a minor elimination pathway. The renal clearance for naltrexone ranges from 30 to 127 mL/min and suggests that renal elimination is primarily by glomerular filtration.
    Half life 4 hours for naltrexone and 13 hours for the active metabolite 6 beta-naltrexol.
    Clearance
    • ~ 3.5 L/min [after IV administration]
    Toxicity In the mouse, rat and guinea pig, the oral LD50s were 1,100-1,550 mg/kg; 1,450 mg/kg; and 1,490 mg/kg; respectively. High doses of naltrexone (generally ≥1,000 mg/kg) produce salivation, depression/reduced activity, tremors, and convulsions.
    Affected organisms
    • Humans and other mammals
    Pathways Not Available
    理化性质
    Properties
    State solid
    Experimental Properties
    Property Value Source
    melting point 168-170 °C PhysProp
    water solubility 100 mg/mL (as hydrochloride salt) Not Available
    logP 1.92 HANSCH,C ET AL. (1995)
    Predicted Properties
    Property Value Source
    water solubility 3.07e+00 g/l ALOGPS
    logP 2.07 ALOGPS
    logP 1.36 ChemAxon
    logS -2 ALOGPS
    pKa (strongest acidic) 7.39 ChemAxon
    pKa (strongest basic) 11.54 ChemAxon
    physiological charge 1 ChemAxon
    hydrogen acceptor count 5 ChemAxon
    hydrogen donor count 2 ChemAxon
    polar surface area 70 ChemAxon
    rotatable bond count 2 ChemAxon
    refractivity 91.5 ChemAxon
    polarizability 35.97 ChemAxon
    药物相互作用
    食物相互作用
    • Take without regard to meals.

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