请输入您要查询的百科知识：

　

词条 Naltrexone
释义

  1. Medical uses

     Alcoholism  Opioid use   Others  Available forms 

  2. Contraindications

  3. Side effects

  4. Pharmacology

     Pharmacodynamics  Mechanism of action  Pharmacokinetics  Pharmacogenetics 

  5. Chemistry

     Analogues 

  6. History

  7. Society and culture

     Generic names  Brand names  Controversies 

  8. Research

     Depersonalization  Low-dose  Self-injury  Behavioral disorders  Interferon alpha 

  9. See also

  10. References

{{Distinguish|Naloxone|Nalmexone}}{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 464372546
| IUPAC_name = (4R,4aS,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7-one
| image = Naltrexone_skeletal.svg
| width = 200px
| image2 = Naltrexone-3D-balls.png
| width2 = 250px
| tradename = ReVia, Vivitrol, others
| Drugs.com = {{drugs.com|monograph|naltrexone}}
| MedlinePlus = a685041
| pregnancy_AU = B3
| pregnancy_US = C
| legal_AU = S4
| legal_CA = Rx-only
| legal_UK = POM
| legal_US = Rx-only
| legal_status = Rx-only
| routes_of_administration = By mouth, intramuscular injection, subcutaneous implant
| bioavailability = 5–40%
| protein_bound = 21%
| metabolism = Liver
| elimination_half-life = Naltrexone: 4 hours
6β-Naltrexol: 13 hours
| excretion = Urine
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 16590-41-3
| ATC_prefix = N07
| ATC_suffix = BB04
| ATC_supplemental =
| PubChem = 5360515
| IUPHAR_ligand = 1639
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00704
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4514524
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 5S6W795CQM
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D05113
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 7465
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 19019
| synonyms = EN-1639A; UM-792; N-Cyclopropyl-methylnoroxymorphone; N-Cyclopropylmethyl-14-hydroxydihydro-morphinone; 17-(Cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxymorphinan-6-one
| C=20 | H=23 | N=1 | O=4
| molecular_weight = 341.401 g/mol
| SMILES = O=C4[C@@H]5Oc1c2c(ccc1O)C[C@H]3N(CC[C@]25[C@@]3(O)CC4)CC6CC6
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = DQCKKXVULJGBQN-XFWGSAIBSA-N
| melting_point = 169
}}Naltrexone, sold under the brand names ReVia and Vivitrol among others, is a medication primarily used to manage alcohol or opioid dependence.[1] An opioid-dependent person should not receive naltrexone before detoxification.[1] It is taken by mouth or by injection into a muscle.[1] Effects begin within 30 minutes.[1] A decreased desire for opioids, though, may take a few weeks.[1]

Side effects may include trouble sleeping, anxiety, nausea, and headaches.[1] In those still on opioids, opioid withdrawal may occur.[1] Use is not recommended in people with liver failure.[1] It is unclear if use is safe during pregnancy.[1][1] Naltrexone is an opioid antagonist and works by blocking the effects of opioids, both those from inside and outside the body.[2]

Naltrexone was first made in 1965 and was approved for medical use in the United States in 1984.[2][3] As of 2017, the wholesale cost of tablets is about US$0.74 per day in the US.[4][5] The extended-release injections cost about $1,267 per month ($41.20 per day).[5] Naltrexone, as bupropion/naltrexone, is also used to treat obesity.[6]

{{TOC limit|3}}

Medical uses

Alcoholism

Naltrexone has been best studied as a treatment for alcoholism.[7] Naltrexone has been shown to decrease the amount and frequency of drinking.[8] It does not appear to change the percentage of people drinking.[9] Its overall benefit has been described as "modest".[10]

Acamprosate may work better than naltrexone for eliminating drinking, while naltrexone may decrease the desire for alcohol to a greater extent.[11]

The Sinclair method is a method of using opiate antagonists such as naltrexone to treat alcoholism. The person takes the medication about an hour (and only then) before drinking to avoid side effects that arise from chronic use.[12][13] The opioid antagonist blocks the positive-reinforcement effects of alcohol and allows the person to stop or reduce drinking.[13]

Opioid use

Long-acting injectable naltrexone decreases heroin use more than placebo.[14] It has benefits over methadone and buprenorphine in that it is not a restricted medication.[14] It may decrease cravings for opioids after a number of weeks, and decreases the risk of overdose.[2][15] It is given once per month and has better compliance than the oral formulation.[16]

A 2011 review found insufficient evidence to determine the effect of naltrexone taken by mouth in opioid dependence.[17] While some do well with this formulation, it must be taken daily, and a person whose cravings become overwhelming can obtain opioid intoxication simply by skipping a dose. Due to this issue, the usefulness of oral naltrexone in opioid use disorders is limited by the low retention in treatment. Naltrexone by mouth remains an ideal treatment for a small number of people with opioid use, usually those with a stable social situation and motivation. With additional contingency management support, naltrexone may be effective in a broader population.[18]

Others

Naltrexone is not useful for quitting smoking.[19]

Available forms

Naltrexone is available and most commonly used in the form of an oral tablet (50 mg).[34] Vivitrol, a naltrexone formulation for depot injection containing 380 mg of the medication per vial, is also available.[34][20] Additionally, naltrexone subcutaneous implants that are surgically implanted are available.[21] While these are manufactured in Australia, they are not authorized for use within Australia, but only for export.[22] By 2009, naltrexone implants showed encouraging results.[23]

Contraindications

Naltrexone should not be used by persons with acute hepatitis or liver failure, or those with recent opioid use (typically 7–10 days).

Side effects

The most common side effects reported with naltrexone are gastrointestinal complaints such as diarrhea and abdominal cramping. These adverse effects are analogous to the symptoms of opioid withdrawal, as the mu receptor blockade will increase GI motility.

Naltrexone has been reported to cause liver damage (when given at doses higher than recommended). It carries an FDA boxed warning for this rare side effect. Due to these reports, some physicians may check liver function tests prior to starting naltrexone, and periodically thereafter. Concerns for liver toxicity initially arose from a study of nonaddicted obese patients receiving 300 mg of naltrexone.[24] Subsequent studies have suggested limited toxicity in other patient populations.

Naltrexone should not be started until several (typically 7-10) days of abstinence from opioids have been achieved. This is due to the risk of acute opioid withdrawal if naltrexone is taken, as naltrexone will displace most opioids from their receptors. The time of abstinence may be shorter than 7 days, depending on the half-life of the specific opioid taken. Some physicians use a naloxone challenge to determine whether an individual has any opioids remaining. The challenge involves giving a test dose of naloxone and monitoring for opioid withdrawal. If withdrawal occurs, naltrexone should not be started.[25]

Pharmacology

Pharmacodynamics

Naltrexone at opioid receptors
Affinities ({{abbrlink|Ki|Inhibitor constant) Ratio Ref
MOR|μ-Opioid receptorDOR|δ-Opioid receptorKOR|κ-Opioid receptor MOR:DOR:KOR
1.0 nM
0.0825 nM 		149 nM
8.02 nM 		3.9 nM
0.509 nM 		1:149:4
1:97:6 		[26]
[27]

Naltrexone and its active metabolite 6β-naltrexol are competitive antagonists at the μ-opioid receptor (MOR), the κ-opioid receptor (KOR) to a lesser extent, and, to a far lesser extent, at the δ-opioid receptor (DOR).[28]

Mechanism of action

The blockade of opioid receptors is the basis behind naltrexone's action in the management of opioid dependence—it reversibly blocks or attenuates the effects of opioids. Its mechanism of action in alcohol dependence is not fully understood, but as an opioid receptor antagonist is likely to be due to the modulation of the dopaminergic mesolimbic pathway (one of the primary centers for risk-reward analysis in the brain, and a tertiary "pleasure center") which is hypothesized to be a major center of the reward associated with addiction that all major drugs of abuse are believed to activate.{{Citation needed|date=December 2009}} Mechanism of action may be antagonism to endogenous opioids such as tetrahydropapaveroline, whose production is augmented in the presence of alcohol.[29]

Pharmacokinetics

Naltrexone is metabolized in the liver mainly to 6β-naltrexol by the enzyme dihydrodiol dehydrogenase. Other metabolites include 2-hydroxy-3-methoxy-6β-naltrexol and 2-hydroxy-3-methoxy-naltrexone. These are then further metabolized by conjugation with glucuronide.{{Citation needed|date=June 2017}} The plasma half-life of naltrexone and its metabolite 6β-naltrexol are about 4 hours and 13 hours, respectively.{{Citation needed|date=June 2017}}

Pharmacogenetics

Tentative evidence suggests that family history and presence of the Asn40Asp polymorphism predicts naltrexone being effective.[30][31]

Chemistry

Naltrexone can be described as a substituted oxymorphone – here the tertiary amine methyl-substituent is replaced with methylcyclopropane. Naltrexone is the N-cyclopropylmethyl derivative of oxymorphone.{{Citation needed|date=June 2017}}

Analogues

The closely related medication, methylnaltrexone, is used to treat opioid-induced constipation, but does not treat addiction as it does not cross the blood–brain barrier. Nalmefene is similar to naltrexone and is used for the same purposes as naltrexone. Naltrexone should not be confused with naloxone, which is used in emergency cases of opioid overdose. Other related opioid antagonists include nalodeine and samidorphan.

History

Naltrexone was first synthesized in 1963 by Metossian at Endo Laboratories, a small pharmaceutical company in New York City.[32] It was characterized by Blumberg, Dayton, and Wolf in 1965 and was found to be an orally active, long-acting, and very potent opioid antagonist.[32][33][34][3] The drug showed advantages over earlier opioid antagonists such as cyclazocine, nalorphine, and naloxone, including its oral activity, a long duration of action allowing for once-daily administration, and a lack of dysphoria, and was selected for further development.[3] It was patented by Endo Laboratories in 1967 under the developmental code name EN-1639A and Endo Laboratories was acquired by DuPont in 1969.[35] Clinical trials for opioid dependence began in 1973, and a developmental collaboration of DuPont with the National Institute on Drug Abuse for this indication started the next year in 1974.[35] The drug was approved by the FDA for the oral treatment of opioid dependence in 1984, with the brand name Trexan, and for the oral treatment of alcohol dependence in 1995, when the brand name was changed by DuPont to ReVia.[35][36] A depot formulation for intramuscular injection was approved by the FDA under the brand name Vivitrol for alcohol dependence in 2006 and opioid dependence in 2010.[20][36]

Society and culture

Generic names

Naltrexone is the generic name of the drug and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|BAN|British Approved Name}}, {{abbrlink|DCF|Dénomination Commune Française}}, and {{abbrlink|DCIT|Denominazione Comune Italiana}}, while naltrexone hydrochloride is its {{abbrlink|USP|United States Pharmacopeia}} and {{abbrlink|BANM|British Approved Name}}.[60][61][62][63]

Brand names

Naltrexone is or has been marketed under a variety of brand names, including Adepend, Antaxone, Celupan, Depade, Nalorex, Narcoral, Nemexin, Revia/ReVia, Trexan, and Vivitrol.[37][38][39][40] It is also marketed in combination with bupropion (bupropion/naltrexone) as Contrave and was marketed with morphine (morphine/naltrexone) as Embeda.[40] A combination of naltrexone with buprenorphine (buprenorphine/naltrexone) has been developed, but has not been marketed.[41]

Controversies

The FDA authorized use of injectable naltrexone for opioid addiction using a single study[42] that was led by Evgeny Krupitsky at Bekhterev Research Psychoneurological Institute, St Petersburg State Pavlov Medical University, St Petersburg, Russia,[43] a country where opioid agonists such as methadone and buprenorphine are not available. The study was a "double-blind, placebo-controlled, randomized", 24-week trial running "from July 3, 2008, through October 5, 2009" with "250 patients with opioid dependence disorder" at "13 clinical sites in Russia" on the use of injectable naltrexone (XR-NTX) for opioid dependence. The study was funded by the Boston-based biotech Alkermes firm which produces and markets naltrexone in the United States. A 2011 article reported that this single trial of naltrexone was performed not by comparing it to the best available, evidence-based treatment (methadone or buprenorphine), but by comparing it with a placebo.[44] A subsequent RCT in Norway did compare injectable naltrexone to buprenorphine and found them to be similar in outcomes.[45]

In May 2017, United States Secretary of Health and Human Services Tom Price, praised [Vivitrol] as the future of opioid addiction treatment after visiting the company's plant in Ohio.[74] His remarks set off sharp criticism with almost 700 experts in the field of substance abuse submitting a letter to Price cautioning him about Vivitrol's "marketing tactics" and warning him that his comment "ignore widely accepted science".[46] The experts pointed out that Vivitrol's competitors, buprenorphine and methadone, are "less expensive", "more widely used", and have been "rigorously studied".

Price had claimed that buprenorphine and methadone were "simply substitute[s]" for "illicit drugs"[47] whereas according to the letter, "the substantial body of research evidence supporting these treatments is summarized in guidance from within your own agency, including the Substance Abuse and Mental Health Services Administration, the US Surgeon General, the National Institute on Drug Abuse, and the Centers for Disease Control and Prevention. To briefly summarize, buprenorphine and methadone have been demonstrated to be highly effective in managing the core symptoms of opioid use disorder, reducing the risk of relapse and fatal overdose, and encouraging long-term recovery."[46]

According to a June 11, 2017, The New York Times article, Alkermes "has spent years coaxing, with a deft lobbying strategy that has targeted lawmakers and law enforcement officials. The company has spent millions of dollars on contributions to officials struggling to stem the epidemic of opioid abuse. It has also provided thousands of free doses to encourage the use of Vivitrol in jails and prisons, which have by default become major detox centers".[47]

Research

Depersonalization

Naltrexone is sometimes used in the treatment of dissociative symptoms such as depersonalization and derealization.[48][49] Some studies suggest it might help.[50] Other small, preliminary studies have also shown benefit.[48][49] Blockade of the KOR by naltrexone and naloxone is thought to be responsible for their effectiveness in ameliorating depersonalization and derealization.[48][49] Since these drugs are less efficacious in blocking the KOR relative to the MOR, higher doses than typically used seem to be necessary.[48][49]

Low-dose

{{Main|Low-dose naltrexone}}

"Low-dose naltrexone" (LDN) describes the "off-label" use of naltrexone at low doses for diseases not related to chemical dependency or intoxication, such as multiple sclerosis.[88] More research needs to be done before it can be recommended for clinical use.

Although some scientific studies show its efficacy in some conditions such as fibromyalgia,[51] other, more dramatic claims for its use in conditions such as cancer and HIV have less scientific support.[52] This treatment has received significant attention on the Internet, especially through websites run by organizations promoting its use.[53]

Self-injury

One study suggests that self-injurious behaviors present in persons with developmental disabilities (including autism) can sometimes be remedied with naltrexone.[54]

In these cases, the self-injury is believed to be done to release beta-endorphin, which binds to the same receptors as heroin and morphine.[55] If the "rush" generated by self-injury is removed, the behavior may stop.

Behavioral disorders

Some indications exist that naltrexone might be beneficial in the treatment of impulse-control disorders such as kleptomania, compulsive gambling, or trichotillomania (compulsive hair pulling), but evidence of its effectiveness for gambling is conflicting.[56][57][58] A 2008 case study reported successful use of naltrexone in suppressing and treating an internet pornography addiction.[59]

Interferon alpha

Naltrexone is effective in suppressing the cytokine-mediated adverse neuropsychiatric effects of interferon alpha therapy.[60][61]

See also

  • Opioid antagonist § List of opioid antagonists
  • One Little Pill (2014 film) - documentary about using naltrexone to treat alcohol use disorder

References

1. ^{{cite journal|last1=Tran|first1=TH|last2=Griffin|first2=BL|last3=Stone|first3=RH|last4=Vest|first4=KM|last5=Todd|first5=TJ|title=Methadone, Buprenorphine, and Naltrexone for the Treatment of Opioid Use Disorder in Pregnant Women.|journal=Pharmacotherapy|date=July 2017|volume=37|issue=7|pages=824–839|doi=10.1002/phar.1958|pmid=28543191}}
2. ^1 2 3 4 5 6 7 8 9 10 11 {{cite web|title=Naltrexone Monograph for Professionals - Drugs.com|url=https://www.drugs.com/monograph/naltrexone.html|website=Drugs.com|publisher=American Society of Health-System Pharmacists|accessdate=9 November 2017|deadurl=no|archiveurl=https://web.archive.org/web/20171109134845/https://www.drugs.com/monograph/naltrexone.html|archivedate=9 November 2017|df=}}
3. ^1 2 {{cite book|last1=Sadock|first1=Benjamin J.|last2=Sadock|first2=Virginia A.|last3=Sussman|first3=Norman|title=Kaplan & Sadock's Pocket Handbook of Psychiatric Drug Treatment|date=2012|publisher=Lippincott Williams & Wilkins|isbn=9781451154467|page=265|url=https://books.google.ca/books?id=qp-H3UruKvIC&pg=PT265|language=en|deadurl=no|archiveurl=https://web.archive.org/web/20171205042100/https://books.google.ca/books?id=qp-H3UruKvIC&pg=PT265|archivedate=2017-12-05|df=}}
4. ^{{cite web|url=http://www.whocc.no/atc_ddd_index/?code=N07BB04|title=Naltrexone|website=ATC/DDD Index|publisher=WHO Collaborating Centre for Drug Statistics Methodology|access-date=11 July 2016|quote="DDD ... 50 mg"|deadurl=no|archiveurl=https://web.archive.org/web/20160303220724/http://www.whocc.no/atc_ddd_index/?code=N07BB04|archivedate=3 March 2016|df=}}
5. ^1 {{cite web|title=NADAC as of 2017-11-29|url=https://data.medicaid.gov/Drug-Pricing-and-Payment/NADAC-as-of-2017-11-29/pmhw-skdi|website=Centers for Medicare and Medicaid Services|accessdate=3 December 2017|language=en|deadurl=no|archiveurl=https://web.archive.org/web/20171203153928/https://data.medicaid.gov/Drug-Pricing-and-Payment/NADAC-as-of-2017-11-29/pmhw-skdi|archivedate=3 December 2017|df=}}
6. ^{{cite journal|title=Naltrexone/bupropion for obesity.|journal=Drug and Therapeutics Bulletin|date=November 2017|volume=55|issue=11|pages=126–129|doi=10.1136/dtb.2017.11.0550|pmid=29117992}}
7. ^{{cite journal|last1=Aboujaoude|first1=E|last2=Salame|first2=WO|title=Naltrexone: A Pan-Addiction Treatment?|journal=CNS Drugs|date=August 2016|volume=30|issue=8|pages=719–33|doi=10.1007/s40263-016-0373-0|pmid=27401883}}
8. ^{{cite journal|last1=Rösner|first1=S|last2=Hackl-Herrwerth|first2=A|last3=Leucht|first3=S|last4=Vecchi|first4=S|last5=Srisurapanont|first5=M|last6=Soyka|first6=M|title=Opioid antagonists for alcohol dependence.|journal=The Cochrane Database of Systematic Reviews|date=8 December 2010|issue=12|pages=CD001867|pmid=21154349|doi=10.1002/14651858.CD001867.pub2}}
9. ^{{cite journal |doi=10.1111/add.12875 |pmid=25664494 |title=The efficacy of acamprosate and naltrexone in the treatment of alcohol dependence, Europe versus the rest of the world: A meta-analysis |journal=Addiction |volume=110 |issue=6 |pages=920–30 |year=2015 |last1=Donoghue |first1=Kim |last2=Elzerbi |first2=Catherine |last3=Saunders |first3=Rob |last4=Whittington |first4=Craig |last5=Pilling |first5=Stephen |last6=Drummond |first6=Colin }}
10. ^{{cite journal |doi=10.2174/138161210791516459 |pmid=20482515 |title=Efficacy and Tolerability of Naltrexone in the Management of Alcohol Dependence |journal=Current Pharmaceutical Design |volume=16 |issue=19 |pages=2091–7 |year=2010 |last1=c. Garbutt |first1=James }}
11. ^{{cite journal |doi=10.1111/j.1360-0443.2012.04054.x |pmid=23075288 |pmc=3970823 |title=Meta-analysis of naltrexone and acamprosate for treating alcohol use disorders: When are these medications most helpful? |journal=Addiction |volume=108 |issue=2 |pages=275–93 |date=October 17, 2012 |last1=Maisel |first1=Natalya C. |last2=Blodgett |first2=Janet C. |last3=Wilbourne |first3=Paula L. |last4=Humphreys |first4=Keith |last5=Finney |first5=John W. }}
12. ^{{cite web|last1=Anderson|first1=Kenneth|title=Drink Your Way Sober with Naltrexone|url=https://www.psychologytoday.com/blog/overcoming-addiction/201307/drink-your-way-sober-naltrexone|website=Psychology Today|accessdate=18 July 2016|date=Jul 28, 2013|deadurl=no|archiveurl=https://web.archive.org/web/20160917232955/https://www.psychologytoday.com/blog/overcoming-addiction/201307/drink-your-way-sober-naltrexone|archivedate=17 September 2016|df=}}
13. ^1 {{cite journal |doi=10.1093/alcalc/36.1.2 |pmid=11139409 |title=Evidence about the use of naltrexone and for different ways of using it in the treatment of alcoholism |journal=Alcohol and Alcoholism |volume=36 |issue=1 |pages=2–10 |year=2001 |last1=Sinclair |first1=J. D. }}
14. ^1 {{cite journal|last1=Sharma|first1=A|last2=Kelly|first2=SM|last3=Mitchell|first3=SG|last4=Gryczynski|first4=J|last5=O'Grady|first5=KE|last6=Schwartz|first6=RP|title=Update on Barriers to Pharmacotherapy for Opioid Use Disorders.|journal=Current Psychiatry Reports|date=June 2017|volume=19|issue=6|pages=35|doi=10.1007/s11920-017-0783-9|pmid=28526967}}
15. ^{{cite journal|last1=Sharma|first1=B|last2=Bruner|first2=A|last3=Barnett|first3=G|last4=Fishman|first4=M|title=Opioid Use Disorders.|journal=Child and Adolescent Psychiatric Clinics of North America|date=July 2016|volume=25|issue=3|pages=473–87|doi=10.1016/j.chc.2016.03.002|pmid=27338968|pmc=4920977}}
16. ^{{cite journal |doi=10.1001/archpsyc.63.2.210 |pmid=16461865 |pmc=4200530 |title=Injectable, Sustained-Release Naltrexone for the Treatment of Opioid Dependence |journal=Archives of General Psychiatry |volume=63 |issue=2 |pages=210–8 |year=2006 |last1=Comer |first1=Sandra D. |last2=Sullivan |first2=Maria A. |last3=Yu |first3=Elmer |last4=Rothenberg |first4=Jami L. |last5=Kleber |first5=Herbert D. |last6=Kampman |first6=Kyle |last7=Dackis |first7=Charles |last8=o'Brien |first8=Charles P. }}
17. ^{{cite journal|last1=Minozzi|first1=S|last2=Amato|first2=L|last3=Vecchi|first3=S|last4=Davoli|first4=M|last5=Kirchmayer|first5=U|last6=Verster|first6=A|title=Oral naltrexone maintenance treatment for opioid dependence.|journal=The Cochrane Database of Systematic Reviews|date=13 April 2011|issue=4|pages=CD001333|doi=10.1002/14651858.CD001333.pub4|pmid=21491383}}
18. ^{{cite journal |doi=10.1111/j.1360-0443.2006.01369.x |pmid=16548929 |title=Efficacy of maintenance treatment with naltrexone for opioid dependence: A meta-analytical review |journal=Addiction |volume=101 |issue=4 |pages=491–503 |year=2006 |last1=Johansson |first1=Björn Axel |last2=Berglund |first2=Mats |last3=Lindgren |first3=Anna }}
19. ^{{cite journal|first1=Sean P.|last1=David|first2=Tim|last2=Lancaster|first3=Lindsay F.|last3=Stead|first4=A. Eden|last4=Evins|title=Opioid antagonists for smoking cessation|journal=The Cochrane Database of Systematic Reviews|date=6 June 2013|issn=1469-493X|pages=CD003086|issue=6|pmid=23744347|pmc=4038652|doi=10.1002/14651858.CD003086.pub3|first5=Judith J.|last5=Prochaska}}
20. ^1 "Alcoholism Once A Month Injectable Drug, Vivitrol, Approved By FDA {{webarchive|url=https://web.archive.org/web/20090105124047/http://www.medicalnewstoday.com/articles/41707.php |date=2009-01-05 }}," Medical News Today, April 16, 2006.
21. ^{{cite web | url = https://www.ebs.tga.gov.au/ebs/ANZTPAR/PublicWeb.nsf/cuMedicines?OpenView | title = Australian Register of Therapeutic Goods Medicines | accessdate = 2009-03-22 | author = Therapeutic Goods Administration | authorlink = | format = Online database of approved medicines | deadurl = no | archiveurl = https://web.archive.org/web/20090514095145/https://www.ebs.tga.gov.au/ebs/ANZTPAR/PublicWeb.nsf/cuMedicines?OpenView | archivedate = 2009-05-14 | df = }}
22. ^{{cite web| url = https://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs%2FPublicHTML%2FpdfStore.nsf&docid=12AA89E8C8E53B46CA257FA7004211EE&agid=(PrintDetailsPublic)&actionid=1 | title = Australian Register of Therapeutic Goods Medicines | accessdate = 2017-04-27 | author = Therapeutic Goods Administration| authorlink = | format = Online database of approved medicines, specific entry for "O'Neil Long Acting Naltrexone Implant" }}
23. ^{{cite journal |doi=10.1001/archgenpsychiatry.2009.130 |pmid=19805701 |title=Improving Clinical Outcomes in Treating Heroin Dependence |journal=Archives of General Psychiatry |volume=66 |issue=10 |pages=1108–15 |year=2009 |last1=Hulse |first1=Gary K. |last2=Morris |first2=Noella |last3=Arnold-Reed |first3=Diane |last4=Tait |first4=Robert J. }}
24. ^{{cite journal |pmid=3092099 |url=https://archives.drugabuse.gov/pdf/monographs/download67.html |year=1986 |author1=Pfohl |first1=David N. |title=Naltrexone hydrochloride (Trexan): A review of serum transaminase elevations at high dosage |journal=NIDA Research Monograph |volume=67 |pages=66–72 |last2=Allen |first2=John I. |last3=Atkinson |first3=Richard L. |last4=Knopman |first4=David S. |last5=Malcolm |first5=Robert J. |last6=Mitchell |first6=James E. |last7=Morley |first7=John E. |deadurl=no |archiveurl=https://web.archive.org/web/20170121150620/https://archives.drugabuse.gov/pdf/monographs/download67.html |archivedate=2017-01-21 |df= }}
25. ^Galanter, Marc; Kleber, Herbert. The American Psychiatric Publishing Textbook of Substance Abuse Treatment, 4th Edition. {{ISBN|1585622761}}{{page needed|date=January 2017}}
26. ^{{cite journal | vauthors = Raynor K, Kong H, Chen Y, Yasuda K, Yu L, Bell GI, Reisine T | title = Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors | journal = Mol. Pharmacol. | volume = 45 | issue = 2 | pages = 330–4 | year = 1994 | pmid = 8114680 | doi = | url = http://molpharm.aspetjournals.org/content/45/2/330.short}}
27. ^{{cite journal |pmid=7562497 |url=http://jpet.aspetjournals.org/content/274/3/1263.short |year=1995 |author1=Codd |first1=E. E. |title=Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: Structural determinants and role in antinociception |journal=The Journal of Pharmacology and Experimental Therapeutics |volume=274 |issue=3 |pages=1263–70 |last2=Shank |first2=R. P. |last3=Schupsky |first3=J. J. |last4=Raffa |first4=R. B. |deadurl=no |archiveurl=https://web.archive.org/web/20170202020241/http://jpet.aspetjournals.org/content/274/3/1263.short |archivedate=2017-02-02 |df= }}
28. ^{{cite journal |doi=10.1007/s40263-013-0096-4 |pmid=23881605 |pmc=4600601 |title=Targeted Opioid Receptor Antagonists in the Treatment of Alcohol Use Disorders |journal=CNS Drugs |volume=27 |issue=10 |pages=777–87 |year=2013 |last1=Niciu |first1=Mark J. |last2=Arias |first2=Albert J. }}
29. ^{{cite journal |doi=10.1016/S0024-3205(96)00597-8 |pmid=9000113 |title=Alcohol induces formation of morphine precursors in the striatum of rats |journal=Life Sciences |volume=60 |issue=2 |pages=79–89 |year=1996 |last1=Haber |first1=Hanka |last2=Roske |first2=Irmgard |last3=Rottmann |first3=Matthias |last4=Georgi |first4=Monika |last5=Melzig |first5=Matthias F. }}
30. ^{{cite journal |doi=10.1111/j.1530-0277.2011.01633.x |pmid=21895723 |pmc=3249007 |title=The Role of the Asn40Asp Polymorphism of the Mu Opioid Receptor Gene (OPRM1) on Alcoholism Etiology and Treatment: A Critical Review |journal=Alcoholism: Clinical and Experimental Research |volume=36 |issue=3 |pages=385–94 |year=2012 |last1=Ray |first1=Lara A. |last2=Barr |first2=Christina S. |last3=Blendy |first3=Julie A. |last4=Oslin |first4=David |last5=Goldman |first5=David |last6=Anton |first6=Raymond F. }}
31. ^{{cite journal |last1=Garbutt |first1=JC |last2=Greenblatt |first2=AM |last3=West |first3=SL |last4=Morgan |first4=LC |last5=Kampov-Polevoy |first5=A |last6=Jordan |first6=HS |last7=Bobashev |first7=GV |title=Clinical and biological moderators of response to naltrexone in alcohol dependence: a systematic review of the evidence. |journal=Addiction |date=August 2014 |volume=109 |issue=8 |pages=1274–84 |doi=10.1111/add.12557 |pmid=24661324}}
32. ^1 {{cite book|author=National Research Council (U.S.). Committee on Problems of Drug Dependence|title=Report of the Thirty-sixth Annual Scientific Meeting: Committee on Problems of Drug Dependence, Mexico City, March 10-14, 1974|url=https://books.google.com/books?id=pEYrAAAAYAAJ&pg=PA265|year=1974|publisher=National Academies|pages=265–|id=NAP:13963}}
33. ^{{cite book|author1=Howard Padwa|author2=Jacob Cunningham|title=Addiction: A Reference Encyclopedia|url=https://books.google.com/books?id=hdMAnL5neAAC&pg=PA207|year=2010|publisher=ABC-CLIO|isbn=978-1-59884-229-6|pages=207–}}
34. ^{{cite book|author=G Bennett|title=Treating Drug Abusers|url=https://books.google.com/books?id=ft6IAgAAQBAJ&pg=PT112|date=14 January 2004|publisher=Routledge|isbn=978-1-134-93173-6|pages=112–}}
35. ^1 2 {{cite book|author=Joseph Wouk|title=Google Ldn !|url=https://books.google.com/books?id=9hOBAgAAQBAJ&pg=RA1-PA78|date=1 March 2009|publisher=Lulu.com|isbn=978-0-578-00439-6|pages=78–88}}
36. ^1 2 3 {{cite book|author=H. Thomas Milhorn|title=Substance Use Disorders: A Guide for the Primary Care Provider|url=https://books.google.com/books?id=wH86DwAAQBAJ&pg=PA88|date=17 October 2017|publisher=Springer International Publishing|isbn=978-3-319-63040-3|pages=88–}}
37. ^1 {{cite book|author=J. Elks|title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA851|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=851–}}
38. ^1 {{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA715|year=2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=715–}}
39. ^1 {{cite book|author1=I.K. Morton|author2=Judith M. Hall|title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA189|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=189–}}
40. ^1 2 {{cite web |url=https://www.drugs.com/international/naltrexone.html |title=Archived copy |accessdate=2017-12-04 |deadurl=no |archiveurl=https://web.archive.org/web/20171204114601/https://www.drugs.com/international/naltrexone.html |archivedate=2017-12-04 |df= }}
41. ^{{cite journal | vauthors = McCann DJ | title = Potential of buprenorphine/naltrexone in treating polydrug addiction and co-occurring psychiatric disorders | journal = Clin. Pharmacol. Ther. | volume = 83 | issue = 4 | pages = 627–30 | year = 2008 | pmid = 18212797 | doi = 10.1038/sj.clpt.6100503 | url = }}
42. ^{{cite web|url=https://psmag.com/social-justice/vivitrol-help-control-addictions-57261|title=A Shot in the Dark: Can Vivitrol Help Us Control Our Addictions?|last1=Armstrong|first1=Walter|date=7 May 2013|website=Pacific Standard|deadurl=no|archiveurl=https://web.archive.org/web/20170913135050/https://psmag.com/social-justice/vivitrol-help-control-addictions-57261|archivedate=13 September 2017|df=}}
43. ^{{cite journal |title=Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial |first1=Evgeny |last1=Krupitsky |first2=Edward V. |last2=Nunes |first3=Walter |last3=Ling |first4=Ari |last4=Illeperuma |first5=David R. |last5=Gastfriend |first6=Bernard L. |last6=Silverman |url=https://www.researchgate.net/publication/51086253 |format=PDF |journal=The Lancet |date=April 28, 2011 |volume=377 |issue=9776 |pages=1506–13 |access-date=June 11, 2017 |doi=10.1016/s0140-6736(11)60358-9 |pmid=21529928 |deadurl=no |archiveurl=https://web.archive.org/web/20170912192327/https://www.researchgate.net/profile/Evgeny_Krupitsky/publication/51086253_Krupitsky_E_Nunes_EV_Ling_W_Illeperuma_A_Gastfriend_DR_Silverman_BL_Injectable_extended-release_naltrexone_for_opioid_dependence_a_double-blind_placebo-controlled_multicentre_randomised_trial_Lancet_3/links/0deec521d0385a2aff000000/Krupitsky-E-Nunes-EV-Ling-W-Illeperuma-A-Gastfriend-DR-Silverman-BL-Injectable-extended-release-naltrexone-for-opioid-dependence-a-double-blind-placebo-controlled-multicentre-randomised-trial-L.pdf |archivedate=September 12, 2017 |df= }}
44. ^{{cite journal |doi=10.1016/S0140-6736(11)61333-0 |title=Injectable extended-release naltrexone for opioid dependence – Authors' reply |journal=The Lancet |volume=378 |issue=9792 |pages=666 |year=2011 |last1=Wolfe |first1=Daniel |last2=Carrieri |first2=MP |last3=Dasgupta |first3=Nabarun |last4=Bruce |first4=Douglas |last5=Wodak |first5=Alex }}
45. ^{{cite journal|last1=Tanum|first1=L|last2=Solli|first2=KK|last3=Latif|first3=ZE|last4=Benth|first4=JŠ|last5=Opheim|first5=A|last6=Sharma-Haase|first6=K|last7=Krajci|first7=P|last8=Kunøe|first8=N|title=The Effectiveness of Injectable Extended-Release Naltrexone vs Daily Buprenorphine-Naloxone for Opioid Dependence: A Randomized Clinical Noninferiority Trial|journal=JAMA Psychiatry|date=18 October 2017|doi=10.1001/jamapsychiatry.2017.3206|pmid=29049469|volume=74|issue=12|pages=1197–1205}}
46. ^1 {{cite web |url=https://www.documentcloud.org/documents/3723472-Tom-Price-Letter-Re-MAT.html |title=Letter to Tom Price |date=May 2017 |access-date=June 11, 2017 |deadurl=no |archiveurl=https://web.archive.org/web/20170625103407/http://www.documentcloud.org/documents/3723472-Tom-Price-Letter-Re-MAT.html |archivedate=June 25, 2017 |df= }}
47. ^1 2 {{cite news |url=https://www.nytimes.com/2017/06/11/health/vivitrol-drug-opioid-addiction.html |newspaper=The New York Times |date=June 11, 2017 |access-date=June 11, 2017 |title=Seizing on Opioid Crisis, a Drug Maker Lobbies Hard for Its Product |quote="Advertising for Vivitrol on a subway car in Brooklyn last month. Marketing for the drug has shifted into high gear." |first1=Abby |last1=Goodnough |first2=Kate |last2=Zernike |deadurl=no |archiveurl=https://web.archive.org/web/20170611133547/https://www.nytimes.com/2017/06/11/health/vivitrol-drug-opioid-addiction.html |archivedate=June 11, 2017 |df= }}
48. ^1 2 3 {{cite book|author1=Daphne Simeon|author2=Jeffrey Abugel|title=Feeling Unreal: Depersonalization Disorder and the Loss of the Self|url=https://books.google.com/books?id=ONLyq-mVLuIC&pg=PA166|date=10 October 2008|publisher=Oxford University Press|isbn=978-0-19-976635-2|pages=166–}}
49. ^1 2 3 {{cite book|author1=Ulrich F. Lanius, PhD|author2=Sandra L. Paulsen, PhD|author3=Frank M. Corrigan, MD|title=Neurobiology and Treatment of Traumatic Dissociation: Towards an Embodied Self|url=https://books.google.com/books?id=0i-FAwAAQBAJ&pg=PA489|date=13 May 2014|publisher=Springer Publishing Company|isbn=978-0-8261-0632-2|pages=489–}}
50. ^{{cite journal |doi=10.1586/14737175.8.1.19 |pmid=18088198 |title=Depersonalization disorder: Pharmacological approaches |journal=Expert Review of Neurotherapeutics |volume=8 |issue=1 |pages=19–26 |year=2014 |last1=Sierra |first1=Mauricio }}
51. ^{{cite journal |doi=10.1111/j.1526-4637.2009.00613.x |pmid=19453963 |pmc=2891387 |title=Fibromyalgia Symptoms Are Reduced by Low-Dose Naltrexone: A Pilot Study |journal=Pain Medicine |volume=10 |issue=4 |pages=663–72 |year=2009 |last1=Younger |first1=Jarred |last2=MacKey |first2=Sean }}
52. ^1 {{cite web|last=Novella|first=Steven|title=Low Dose Naltrexone – Bogus or Cutting Edge Science?|url=http://www.sciencebasedmedicine.org/index.php/low-dose-naltrexone-bogus-or-cutting-edge-science/|date=5 May 2010|accessdate=5 July 2011|work=Science-Based Medicine|deadurl=no|archiveurl=https://web.archive.org/web/20110708043917/http://www.sciencebasedmedicine.org/index.php/low-dose-naltrexone-bogus-or-cutting-edge-science/|archivedate=8 July 2011|df=}}
53. ^{{cite web|last=Bowling|first=Allen C.|title=Low-dose naltrexone (LDN) The "411" on LDN|url=http://www.nationalmssociety.org/multimedia-library/momentum-magazine/back-issues/momentum-spring-09/index.aspx|publisher=National Multiple Sclerosis Society|accessdate=6 July 2011|deadurl=yes|archiveurl=https://web.archive.org/web/20111222063116/http://www.nationalmssociety.org/multimedia-library/momentum-magazine/back-issues/momentum-spring-09/index.aspx|archivedate=22 December 2011|df=}}
54. ^{{cite journal |doi=10.1007/BF02684958 |title=Effects of naltrexone on self-injury, stereotypy, and social behavior of adults with developmental disabilities |journal=Journal of Developmental and Physical Disabilities |volume=7 |issue=2 |pages=137–46 |year=1995 |last1=Smith |first1=Stanley G. |last2=Gupta |first2=Krishan K. |last3=Smith |first3=Sylvia H. }}
55. ^{{cite news | publisher=The Reporter | last=Manley | first=Cynthia | date=1998-03-20 | url=http://www.mc.vanderbilt.edu/reporter/index.html?ID=461 | title=Self-injuries may have biochemical base: study | deadurl=no | archiveurl=https://web.archive.org/web/20090105011250/http://www.mc.vanderbilt.edu/reporter/index.html?ID=461 | archivedate=2009-01-05 | df= }}
56. ^{{cite journal |doi=10.1016/j.biopsych.2008.11.022 |pmid=19217077 |laysummary=https://www.sciencedaily.com/releases/2009/04/090401101900.htm |laysource=Science Daily |laydate=April 3, 2009 |title=A Double-Blind, Placebo-Controlled Study of the Opiate Antagonist, Naltrexone, in the Treatment of Kleptomania |journal=Biological Psychiatry |volume=65 |issue=7 |pages=600–6 |year=2009 |last1=Grant |first1=Jon E. |last2=Kim |first2=Suck Won |last3=Odlaug |first3=Brian L. }}
57. ^{{cite web|url=http://ichgcp.net/clinical-trials-registry/NCT00326807|title=A Randomized, Double-Blind, Placebo-Controlled Trial of Naltrexone in the Treatment of Concurrent Alcohol Dependence and Pathological Gambling - ICH GCP - Clinical Trials Registry|publisher=|deadurl=no|archiveurl=https://web.archive.org/web/20150626114447/http://ichgcp.net/clinical-trials-registry/NCT00326807|archivedate=2015-06-26|df=}}
58. ^{{cite journal |doi=10.1016/S0006-3223(01)01079-4 |pmid=11377409 |title=Double-blind naltrexone and placebo comparison study in the treatment of pathological gambling |journal=Biological Psychiatry |volume=49 |issue=11 |pages=914–21 |year=2001 |last1=Kim |first1=Suck Won |last2=Grant |first2=Jon E |last3=Adson |first3=David E |last4=Shin |first4=Young Chul }}
59. ^{{cite journal |doi=10.4065/83.2.226 |pmid=18241634 |title=Internet Sex Addiction Treated with Naltrexone |journal=Mayo Clinic Proceedings |volume=83 |issue=2 |pages=226–30 |year=2008 |last1=Bostwick |first1=J. Michael |last2=Bucci |first2=Jeffrey A. }}
60. ^{{cite journal |doi=10.1016/s0013-7006(05)82400-5 |id={{INIST|16920336}} |pmid=16142050 |title=Hépatite C, Interféron α et dépression : Principales hypothèses physiopathologiques |trans-title=Hepatitis C, interferon a and depression: main physiopathologic hypothesis |language=French |journal=L'Encéphale |volume=31 |issue=3 |pages=349–57 |year=2005 |last1=Vignau |first1=J. |last2=Karila |first2=L. |last3=Costisella |first3=O. |last4=Canva |first4=V. }}
61. ^{{cite journal |pmid=17068950 |url=http://www.psychiatriapsychoterapia.pl/?a=articles_show&id=459 |year=2006 |author1=Małyszczak |first1=Krzysztof |title=Objawy neuropsychiatryczne w trakcie leczenia interferonem alfa |trans-title=Neuropsychiatric symptoms related to interferon alpha |language=Polish |journal=Psychiatria Polska |volume=40 |issue=4 |pages=787–97 |last2=Inglot |first2=Małgorzata |last3=Pawłowski |first3=Tomasz |last4=Czarnecki |first4=Marcin |last5=Rymer |first5=Weronika |last6=Kiejna |first6=Andrzej |deadurl=no |archiveurl=https://web.archive.org/web/20170202010519/http://www.psychiatriapsychoterapia.pl/?a=articles_show&id=459 |archivedate=2017-02-02 |df= }}
{{Antiaddictives}}{{Opioid receptor modulators}}

11 : Alcohol abuse|Cyclopropanes|Diols|Ethers|GABAA receptor negative allosteric modulators|Kappa antagonists|Ketones|Morphinans|Phenols|Opioid antagonists|RTT
随便看

　

开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。

　

Copyright © 2023 OENC.NET All Rights Reserved
京ICP备2021023879号 更新时间：2024/11/11 1:22:11