| 词条 | Naloxegol |
| 释义 |
| IUPAC_name = (5α,6α)-4,5-epoxy-6-(3,6,9,12,15,18,21-heptaoxadocos-1-yloxy)-17-(2-propen-1-yl)morphinan-3,14-diol | image = Naloxegol.svg | width = | image2 = | width2 = | Drugs.com = {{Drugs.com|parent|movantik}} | CAS_number = 854601-70-0 | CAS_supplemental = | ATC_prefix = A06 | ATC_suffix = AH03 | ATC_supplemental = | PubChem = 56959087 | DrugBank = | ChemSpiderID = 28651656 | ChEBI = 82975 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 44T7335BKE | KEGG = D10479 | C= 34| H= 53 | N=1 | O= 11 | molecular_weight = 651.785 g/mol | smiles = COCCOCCOCCOCCOCCOCCOCCO[C@H]1CC[C@]2([C@H]3Cc4ccc(c5c4[C@]2([C@H]1O5)CCN3CC=C)O)O | StdInChI = 1S/C34H53NO11/c1-3-9-35-10-8-33-30-26-4-5-27(36)31(30)46-32(33)28(6-7-34(33,37)29(35)25-26)45-24-23-44-22-21-43-20-19-42-18-17-41-16-15-40-14-13-39-12-11-38-2/h3-5,28-29,32,36-37H,1,6-25H2,2H3/t28-,29+,32-,33-,34+/m0/s1 | StdInChIKey = XNKCCCKFOQNXKV-ZRSCBOBOSA-N | synonyms = NKTR-118 | density = | melting_point = | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = | specific_rotation = | sec_combustion = | bioavailability = | protein_bound = ~4.2% | metabolism = Hepatic (CYP3A) | elimination_half-life = 6–11 h | excretion = Feces (68%), urine (16%) | licence_EU = yes | licence_US = Movantik | tradename = Movantik, Moventig | DailyMedID = | pregnancy_AU = | pregnancy_US = C | pregnancy_category = | legal_AU = | legal_CA = | legal_UK = | legal_US = Rx only | legal_status = | routes_of_administration = Oral }}Naloxegol (INN; PEGylated naloxol;[1] trade names Movantik and Moventig) is a peripherally selective opioid antagonist developed by AstraZeneca, licensed from Nektar Therapeutics, for the treatment of opioid-induced constipation.[2] It was approved in 2014 in adult patients with chronic, non-cancer pain.[3] Doses of 25 mg were found safe and well tolerated for 52 weeks.[4] When given concomitantly with opioid analgesics, naloxegol reduced constipation-related side effects, while maintaining comparable levels of analgesia.[5] Chemically, naloxegol is a pegylated (polyethylene glycol-modified) derivative of α-naloxol. Specifically, the 6-α-hydroxyl group of α-naloxol is connected via an ether linkage to the free hydroxyl group of a monomethoxy-terminated n=7 oligomer of PEG, shown extending at the lower left of the molecule image at right. The "n=7" defines the number of two-carbon ethylenes, and so the chain length, of the attached PEG chain, and the "monomethoxy" indicates that the terminal hydroxyl group of the PEG is "capped" with a methyl group.[6] The pegylation of the 6-α-hydroxyl side chain of naloxol prevents the drug from crossing the blood-brain barrier (BBB).[5] As such, it can be considered the antithesis of the peripherally-acting opiate loperamide which is utilized as an opiate-targeting anti-diarrheal agent that does not cause traditional opiate side-effects due to its inability to accumulate in the central nervous system in normal subjects. Naloxegol was previously a Schedule II drug in the United States because of its chemical similarity to opium alkaloids, but was recently reclassified as a prescription drug after the FDA concluded that the impermeability of the blood-brain barrier to this compound made it non-habit-forming, and so without the potential for abuse—specifically, naloxegol was officially decontrolled on 23 January 2015.[7] As a pure opioid antagonist Naloxegol has no potential for abuse. See also
References and notes1. ^{{cite book | author1 = Roland Seifert | author2 = Thomas Wieland | author3 = Raimund Mannhold |author4=Hugo Kubinyi |author5=Gerd Folkers | title = G Protein-Coupled Receptors as Drug Targets: Analysis of Activation and Constitutive Activity | url = https://books.google.com/books?id=pIrnOKH-7HcC&pg=PA227 | accessdate = 14 May 2012 | date = 17 July 2006 | publisher = John Wiley & Sons | isbn = 978-3-527-60695-5 | page = 227}} {{Laxatives}}{{Opioidergics}}{{nervous-system-drug-stub}}2. ^{{cite web | url = http://www.nektar.com/product_pipeline/cns_pain_oral_nktr-118and119.html | title = Nektar | R&D Pipeline | Products in Development | CNS/Pain | Oral Naloxegol (NKTR-118) and Oral NKTR-119 | work = | accessdate = 2012-05-14 | deadurl = yes | archiveurl = https://web.archive.org/web/20120213133752/http://www.nektar.com/product_pipeline/cns_pain_oral_nktr-118and119.html | archivedate = 2012-02-13 | df = }} 3. ^{{Cite news|url =http://www.astrazeneca-us.com/media/press-releases/Article/20140916-fda-approves-movantik-naloxegol-tablets-cii|title =FDA approves MOVANTIK™ (naloxegol) Tablets C-II for the treatment of opioid-induced constipation in adult patients with chronic non-cancer pain|last =|first =|date =16 September 2014|work =|access-date =|via =|archive-url =https://web.archive.org/web/20150510025921/http://www.astrazeneca-us.com/media/press-releases/Article/20140916-fda-approves-movantik-naloxegol-tablets-cii|archive-date =2015-05-10|dead-url =no|df =}} 4. ^{{Cite journal|url = |title = Randomised clinical trial: the long-term safety and tolerability of naloxegol in patients with pain and opioid-induced constipation.|last = |first = |date = Oct 2014|journal = Aliment. Pharmacol. Ther.|doi = 10.1111/apt.12899|pmid = 25112584|access-date = |volume=40 |pages=771–9}} 5. ^1 {{cite journal | journal = Drugs | date = 2015 | volume = 75 | issue = 4 | pages = 419–425 | doi = 10.1007/s40265-015-0357-2 | title = Naloxegol: a review of its use in patients with opioid-induced constipation | author = Garnock-Jones KP}} 6. ^Technically, the molecule that is attached via the ether link is O-methyl-heptaethylene glycol [that is, methoxyheptaethylene glycol, CH3OCH2CH2O(CH2CH2O)5CH2CH2OH], molecular weight 340.4, CAS number 4437-01-8. See {{cite book | author = Pubchem Staff | year = 2016 | title = PubChem Compound Database | chapter = Compound Summary for CID 526555, Pubchem Compound 4437-01 | url = https://pubchem.ncbi.nlm.nih.gov/compound/4437-01-8#section=Top | access-date = 28 January 2016 | location = Bethesda, MD, USA | publisher = NCBI, U.S. NLM | archive-url = https://web.archive.org/web/20160205030929/http://pubchem.ncbi.nlm.nih.gov/compound/4437-01-8#section=Top#section=Top | archive-date = 2016-02-05 | dead-url = no | df = }} 7. ^{{cite web|url=http://www.deadiversion.usdoj.gov/fed_regs/rules/2015/fr0123_3.htm|title=Schedules of Controlled Substances: Removal of Naloxegol From Control|author=|date=|website=www.deadiversion.usdoj.gov|access-date=2016-02-27|archive-url=https://web.archive.org/web/20160309173010/http://www.deadiversion.usdoj.gov/fed_regs/rules/2015/fr0123_3.htm|archive-date=2016-03-09|dead-url=no|df=}} 6 : Allyl compounds|Diols|Morphinans|Opioid antagonists|Peripherally selective drugs|Synthetic opioids |
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