(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

• ChemBase ID: 585
• Molecular Formular: C20H23NO4
• Molecular Mass: 341.40092
• Monoisotopic Mass: 341.16270822
• SMILES: O1[C@@H]2[C@]34[C@](O)([C@H](N(CC3)CC3CC3)Cc3c4c1c(O)cc3)CCC2=O
• Canonical SMILES: O=C1CC[C@@]2([C@@]34[C@H]1Oc1c4c(C[C@H]2N(CC3)CC2CC2)ccc1O)O
• InChI: InChI=1S/C20H23NO4/c22-13-4-3-12-9-15-20(24)6-5-14(23)18-19(20,16(12)17(13)25-18)7-8-21(15)10-11-1-2-11/h3-4,11,15,18,22,24H,1-2,5-10H2/t15-,18+,19+,20-/m1/s1
• InChIKey: DQCKKXVULJGBQN-XFWGSAIBSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (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
• IUPAC Traditional name: naltrexone
• Brand Name: N-Cyclopropylmethylnoroxymorphone; Naltrexona [INN-Spanish]; Naltrexone Hcl; Naltrexone [Usan:Ban:Inn]; Naltrexonum [INN-Latin]; ReVia; Vivitrex; MorViva; Celupan
• Synonyms: naltrexone; PTI-555; Naltrexone

Database IDs

• CAS Number: 16590-41-3
• PubChem SID: 160964048; 46505333
• PubChem CID: 5360515

CALCULATED PROPERTIES

JChem

• Acid pKa: 10.106068
• H Acceptors: 5
• H Donor: 2
• LogD (pH = 5.5): -1.4911842
• LogD (pH = 7.4): 0.13493212
• Log P: 1.3626752
• Molar Refractivity: 91.5015 cm^3
• Polarizability: 35.902298 Å^3
• Polar Surface Area: 70.0 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.07
• LOG S: -2.05
• Solubility (Water): 3.07e+00 g/l

PROPERTIES

Physical Property

• Solubility: 100 mg/mL (as hydrochloride salt)
• Hydrophobicity(logP): 0.7

DETAILS

DrugBank - DB00704

• Drug Groups: approved; investigational
• Description: 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]
• 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.
• Pharmacology: 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.
• 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
• Biotransformation: 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.
• Absorption: Although well absorbed orally, naltrexone is subject to significant first pass metabolism with oral bioavailability estimates ranging from 5 to 40%.
• Half Life: 4 hours for naltrexone and 13 hours for the active metabolite 6 beta-naltrexol.
• Protein Binding: 21% bound to plasma proteins over the therapeutic dose range.
• 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.
• Distribution: * 1350 L [intravenous administration]
• Clearance: * ~ 3.5 L/min [after IV administration]
• References: 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] ; 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] ; 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]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

REFERENCES

• 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
• 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
• 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