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an oral antagonist against the action of opiates

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/08/22 15:39:50」(JST)

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Naltrexone is an opioid receptor antagonist used primarily in the management of alcohol dependence and opioid dependence. It is marketed in generic form as its hydrochloride salt, naltrexone hydrochloride, and marketed under the trade names Revia and Depade. In some countries including the United States, a once-monthly extended-release injectable formulation is marketed under the trade name Vivitrol. Also in the United States, Methylnaltrexone Bromide, a closely related drug, is marketed as Relistor, for the treatment of opioid induced constipation.

Naltrexone should not be confused with naloxone (which is used in emergency cases of opioid overdose) nor nalorphine. Using naloxone in place of naltrexone can cause acute opioid withdrawal symptoms; conversely, using naltrexone in place of naloxone in an overdose can lead to insufficient opioid antagonism and fail to reverse the overdose.

1 Medical uses
- 1.1 Alcohol dependence
- 1.2 Opioid dependence
- 1.3 Rapid opioid detoxification
- 1.4 Other uses
  - 1.4.1 Depersonalization disorder
  - 1.4.2 Low-dose naltrexone
  - 1.4.3 Tobacco dependence
  - 1.4.4 Self-injurious behaviors
  - 1.4.5 Behavioral addiction
  - 1.4.6 Countering adverse effects of interferon alpha
2 Formulations
3 Adverse effects
4 Contraindications
5 Pharmacogenetics
6 Mechanism of action
7 Structure and pharmacokinetics
8 See also
9 References
10 External links

Medical uses

Alcohol dependence

The main use of naltrexone is for the treatment of alcohol dependence. Naltrexone was approved by the U.S. Food and Drug Administration (FDA) for the treatment of alcohol dependence in 1994, following publication of the first two randomized, controlled trials in 1992. Since then a number of studies have confirmed its efficacy in reducing frequency and severity of relapse to drinking.^[1] The multi-center COMBINE study showed the usefulness of naltrexone in a primary care setting, without adjunct psychotherapy.^[2]

The standard regimen is one 50 mg tablet per day.

Naltrexone has been shown to reduce relapse rates after abstinence in multiple clinical studies.^[3] Additionally there is evidence that naltrexone helps reduce heavy drinking when used in people who continue drinking while taking naltrexone, but that it is less effective in helping patients achieve abstinence.^[4] Some authors argue that naltrexone demonstrated an advantage over placebo in reducing heavy drinking to normal levels rather than trying to achieve abstinence. Patients under what is called the Sinclair Method continue to drink when using naltrexone.^[5]

As noted in the Pharmacogenetics section below, studies since the early 21st century have identified a gene, which is prevalent in roughly 25-30% of the white population, that results in a much more effective response to the use naltrexone in reducing or ending dependence on alcohol. This gene is rarely present among blacks; it is common among 60-70 percent of Asians.^[6]

Opioid dependence

Naltrexone helps patients overcome opioid addiction by blocking the drugs’ euphoric effects. Unlike when used for alcohol dependence (discussed above), naltrexone has little effect on opioid cravings.^[7] Naltrexone has in general been better studied for alcohol dependence than in treating opioid dependence. It is also more frequently used for alcohol, despite originally being approved by the FDA in 1984 for opioid addiction.^[8]

A recent review of studies suggests that more research is needed to show naltrexone's effectiveness in treating opioid dependence (and to compare naltrexone to other options such as methadone and buprenorphine).^[9] While some patients do well with the oral formulation, there is a drawback in that it must be taken daily, and a patient whose cravings become overwhelming can obtain opioid intoxication simply by skipping a dose before resuming opioid use. Due to this issue, the usefulness of oral naltrexone in opioid dependence is limited by the low retention in treatment. Oral naltrexone remains an ideal treatment only for a small part of the opioid-dependent population, usually the ones with an unusually stable social situation and motivation (e.g., opioid-dependent health care professionals). Naltrexone treats the physical dependence on opioids, but further psychosocial interventions (such as counselling and group therapy) are often required to enable people to maintain abstinence.^[10]

Rapid opioid detoxification

Naltrexone is sometimes used for rapid detoxification ("rapid detox") regimens for opioid dependence. The principle of rapid detoxification is to induce opioid-receptor blockage while the patient is in a state of impaired consciousness, so as to attenuate the withdrawal symptoms experienced by the patient. Rapid detoxification under general anaesthesia (sometimes called "ultra-rapid detox") involves an unconscious patient and requires intubation and external ventilation. Rapid detoxification is also possible under lighter sedation. The rapid detoxification procedure is followed by oral naltrexone daily for up to 12 months for opioid dependence management. There are a number of practitioners who will use a naltrexone implant, usually placed in the lower abdomen, to replace the oral naltrexone. This implant procedure has not been shown scientifically to be successful in "curing" subjects of their addiction, though it does provide a better solution than oral naltrexone for medication compliance reasons. There is scientific disagreement as to the safety of this procedure, as well as whether this procedure should be performed under light sedation or general anesthesia, due to the rapid and sometimes severe withdrawal that occurs.^[11]^[12]

Rapid detoxification has been criticised by some for its questionable efficacy in long-term opioid dependence management.^[13] Rapid detoxification has often been misrepresented as a one-off "cure" for opioid dependence, when it is only intended as the initial step in an overall drug rehabilitation regimen. Rapid detoxification is effective for short-term opioid detoxification, but is approximately 10 times more expensive than conventional detoxification procedures. Aftercare can also be an issue,^[13] since at least one well-known center in the United States reported that they will remove an implant from any patient arriving in their facility before admission.^{[citation needed]}^[who?]

Other uses

Depersonalization disorder

Naltrexone is sometimes used in the treatment of depersonalization disorder. While studies have suggested it is less effective than naloxone for treating depersonalization, naloxone is impractical for daily use because it must be injected intravenously. A 2005 naltrexone study demonstrated an average of 30% reduction of depersonalization symptoms, as measured by 3 validated dissociation scales.^[14] Most of the efforts in studying naltrexone for depersonalization thus far have been directed by Dr. Daphne Simeon at the Icahn School of Medicine at Mount Sinai.

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.^[15] Much more research needs to be done before it can be recommended for clinical use.

Although there are scientific studies showing its efficacy in some conditions such as fibromyalgia,^[16] other, more dramatic claims for its use in conditions like cancer and HIV have less scientific support.^[15] This treatment has received significant attention on the Internet, especially through websites run by organizations promoting its use.^[17]

Tobacco dependence

A study done by The Chicago Stop Smoking Research Project at the University of Chicago found that Naltrexone did not help to improve a subject's chance of attaining smoking cessation when compared to a placebo.^[18]

Self-injurious behaviors

Some studies suggest that self-injurious behaviors present in persons with developmental disabilities (including autism) can sometimes be remedied with naltrexone.^[19] In these cases, it is believed that the self-injury is being done to release beta-endorphin, which binds to the same receptors as heroin and morphine.^[20] If the "rush" generated by self-injury is removed, the behavior may stop.

Behavioral addiction

There are indications that naltrexone might be beneficial in the treatment of impulse control disorders such as kleptomania, compulsive gambling, or trichotillomania (compulsive hair pulling), but there is conflicting evidence of its effectiveness for gambling.^[21]^[22]^[23] A 2008 case study reported successful use of naltrexone in suppressing and treating an internet pornography addiction.^[24]^{[dead link]}

Countering adverse effects of interferon alpha

Naltrexone is effective in suppressing the cytokine type mediated adverse neuropsychiatric effects of interferon alpha therapy.^[25]^[26]

Formulations

Depot injectable naltrexone (Vivitrol, formerly Vivitrex, but changed after a request by the FDA) was approved by the FDA on April 13, 2006 for the treatment of alcohol dependence.^[27] This version is made and marketed by Alkermes in the United States, and is marketed by Johnson & Johnson in Russia. Cephalon Inc. originally marketed the drug in the United States, however, Alkermes reclaimed Vivitrol commercialization rights in 2008.^[28] The recommended dose of Vivitrol 380 mg is delivered intramuscularly once a month. The injection should be administered by a healthcare professional.^[29]

Naltrexone Hydrochloride marketed as Naltima-50 (Intas Pharmaceuticals, India)

The clinical trial leading to the approval of Vivitrol showed that when compared with a placebo, 380 mg of Vivitrol resulted in a 25% decrease in the event rate of heavy drinking days and 190 mg resulted in a 17% decrease. The 6-month randomized, double-blind, placebo-controlled study was conducted between February 2002 and September 2003. Of the 899 individuals screened, 627 were diagnosed as alcohol-dependent adults and were randomized to receive treatment. The main outcome measure was the event rate of heavy drinking days in the intent-to-treat population. The study’s authors concluded that: “Long-acting naltrexone was well tolerated and resulted in reductions in heavy drinking among treatment-seeking alcohol dependent patients during 6 months of therapy.”^[30]

The FDA approved Vivitrol on October 12, 2010 for the prevention of relapse to opioid dependence, following opioid detoxification. This injectable version was previously approved only for alcohol dependence. The phase 3 clinical study upon which the FDA granted approval for Vivitrol in treating opioid dependence had an enrollment of 250 patients and treated for six months. Primary outcome measures were percentage of weekly urine tests negative for opioids and length of study retention during the double-blind period. Alkermes presented positive results from this study at the American Psychiatric Association 2010 Annual Meeting in May 2010. The study met its primary efficacy endpoint and data showed that patients treated once-monthly with Vivitrol demonstrated statistically significant higher rates of opioid-free urine screens, compared to patients treated with a placebo, as measured by the cumulative distribution of clean urine screens (p<0.0002).^[31]^[32]

“This drug approval represents a significant advancement in addiction treatment,” said Janet Woodcock, M.D., director of the FDA’s Center Drug Evaluation and Research.^[33] Nora Volkow, M.D., Director of the National Institute on Drug Abuse (NIDA), stated that: “As a depot formulation, dosed monthly, Vivitrol obviates the daily need for patients to motivate themselves to stick to a treatment regimen - a formidable task, especially in the face of multiple triggers of craving and relapse. This new option increases the pharmaceutical choices for treating opioid addiction, and may be seen as advantageous by those unwilling to consider agonist or partial agonist approaches to treatment. NIDA is continuing to support research on Vivitrol's effectiveness in this country, including a focus on criminal justice involved populations transitioning back into the community.”^[34]

A newer option is the naltrexone implant, which must be surgically inserted under the skin. The implant provides a sustained dose of naltrexone to the patient, thereby preventing the problems which may be associated with missing doses. It must be replaced every several months. Naltrexone implants are made by at least three companies, though none have been approved by the U.S. Food and Drug Administration (FDA) or the Australian Therapeutic Goods Administration.^[35] Naltrexone implants have been used successfully in Australia for a number of years as part of a long-term protocol for treating opiate addiction.^[36]

Adverse effects

The most common side effects reported with naltrexone are non-specific gastrointestinal complaints such as diarrhea and abdominal cramping.

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 non-addicted obese patients receiving 300 mg of naltrexone.^[37] Subsequent studies have suggested limited toxicity in other patient populations.

Naltrexone should not be started prior to several (typically 7-10) days of abstinence from opioids. 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.^[8]

It is important that one not attempt to use opioids while using naltrexone. Although naltrexone blocks the opioid receptor, it is possible to override this blockade with very high doses of opioids. However this is quite dangerous and may lead to opioid overdose, respiratory depression, and death. Similarly one will not show normal response to opioid pain medications when taking naltrexone. In a supervised medical setting pain relief is possible but may require higher than usual doses, and the individual should be closely monitored for respiratory depression. All individuals taking naltrexone are encouraged to keep a card or a note in their wallet in case of an injury or another medical emergency. This is to let medical personnel know that special procedures are required if opiate-based painkillers are to be used.

There has been some controversy regarding the use of opioid-receptor antagonists, such as naltrexone, in the long-term management of opioid dependence due to the effect of these agents in sensitizing the opioid receptors. That is, after therapy, the opioid receptors continue to have increased sensitivity for a period during which the patient is at increased risk of opioid overdose.^{[citation needed]} This effect reinforces the necessity of monitoring of therapy and provision of patient support measures by medical practitioners.

Contraindications

Naltrexone (50 mg per day) should not be used by persons with acute hepatitis or liver failure, or those with recent opioid use (typically 7–10 days).

Pharmacogenetics

A naltrexone treatment study by Anton et al., released by the National Institutes of Health in February 2008 and published in the Archives of General Psychiatry, has shown that alcoholics having a certain variant of the opioid receptor gene (G polymorphism of SNP Rs1799971 in the gene OPRM1) demonstrated strong response to naltrexone and were far more likely to experience success at cutting back or discontinuing their alcohol intake altogether, while for those lacking the gene variant, naltrexone appeared to be no different from placebo.^[6] The G allele of OPRM1 is most common in individuals of Asian descent, with 60% to 70% of people of Chinese, Japanese, and Indian ancestry having at least one copy, as opposed to 30% of Europeans and very few Africans.^[38]

Because of the characteristics of the patient group in the US, the first study was done on white patients, and the next without regard for ethnicity. Anton et al. found that patients of African descent did not have much success with naltrexone in treatment for alcohol dependence because of lacking the relevant gene.^[6]

As white patients with the gene had a five times greater rate of success in reducing drinking when given naltrexone than did patients without the gene, when used in a protocol of Medical Management (MM), Anton et al. concluded,

"Because almost 25% of the treatment-seeking population carries the Asp40 allele, genetic testing of individuals before naltrexone treatment might be worth the cost and effort, especially if structured behavioral treatment were not being considered."^[6] This would enable treatment to be targeted by genetics to patients for whom it would be most effective. They noted, "Naltrexone is relatively easy to administer and free of serious adverse effects and, as we observed in the Asp40 carriers we studied, it appears to be highly effective."^[6]

Studies have found naltrexone to be more efficacious among certain white subjects, because of the genetic basis, than among black subjects, who generally do not carry the relevant gene.^[39] A 2009 study of naltrexone as an alcohol dependence treatment among African Americans failed to find any statistically significant differences between naltrexone and a placebo.^[40] Studies have suggested that carriers of the G allele may experience higher levels of craving and stronger "high" upon alcohol consumption, compared to carriers of the dominant allele, and naltrexone somewhat blunts these responses, leading to a reduction in alcohol use in some studies.^[41]

Mechanism of action

Naltrexone and its active metabolite 6-β-naltrexol are competitive antagonists at μ- and κ-opioid receptors, and to a lesser extent at δ-opioid receptors.^[42] The plasma half-life of naltrexone is about 4 h, for 6-β-naltrexol 13 h. The blockade of opioid receptors is the basis behind its action in the management of opioid dependence—it reversibly blocks or attenuates the effects of opioids.

Naltrexone's 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]} Mechanism of action may be antagonism to endogenous opiates such as tetrahydropapaveroline, whose production is augmented in the presence of alcohol.^[43]

Structure and pharmacokinetics

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.

Naltrexone is metabolised mainly to 6β-naltrexol by the liver enzyme dihydrodiol dehydrogenase. Other metabolites include 2-hydroxy-3-methoxy-6β-naltrexol and 2-hydroxy-3-methoxy-naltrexone. These are then further metabolised by conjugation with glucuronide.

References

^ Latt NC, Jurd S, Houseman J, Wutzke SE (June 2002). "Naltrexone in alcohol dependence: a randomised controlled trial of effectiveness in a standard clinical setting". Med J Aust 176 (11): 530–4. PMID 12064984.
^ "Naltrexone or Specialized Alcohol Counseling an Effective Treatment for Alcohol Dependence When Delivered with Medical Management" (Press release). National Institutes of Health. May 2, 2006. Retrieved 2009-04-16.
^ Srisurapanont, M.; Jarusuraisin, N.; Leucht, S.; Vecchi, S.; Srisurapanont, M.; Soyka, M. (2005). Opioid antagonists for alcohol dependence. In Srisurapanont, Manit. "Cochrane Database of Systematic Reviews". Cochrane database of systematic reviews (Online) (12): CD001867. doi:10.1002/14651858.CD001867.pub2. PMID 15674887. edit
^ Pettinati, H. M.; O'Brien, C. P.; Rabinowitz, A. R.; Wortman, S. P.; Oslin, D. W.; Kampman, K. M.; Dackis, C. A. (2006). "The Status of Naltrexone in the Treatment of Alcohol Dependence". Journal of Clinical Psychopharmacology 26 (6): 610–625. doi:10.1097/01.jcp.0000245566.52401.20. PMID 17110818. edit
^ Eskapa, Roy (2008). The Cure for Alcoholism. BenBella Books. p. 35. ISBN 1-933771-55-0.
^ ^a ^b ^c ^d ^e Anton R, Oroszi G, O’Malley S, Couper D, Swift R, Pettinati H, Goldman D (2008). "An Evaluation of Opioid Receptor (OPRM1) as a Predictor of Naltrexone Response in the Treatment of Alcohol Dependence". Archives of General Psychiatry 65 (2): 135–144. doi:10.1001/archpsyc.65.2.135. PMC 2666924. PMID 18250251.
^ Dijkstra BA, De Jong CA, Bluschke SM, Krabbe PF, van der Staak CP (June 2007). "Does naltrexone affect craving in abstinent opioid-dependent patients?". Addict Biol 12 (2): 176–82. doi:10.1111/j.1369-1600.2007.00067.x. PMID 17508990.
^ ^a ^b Galanter, Marc; Kleber, Herbert. The American Psychiatric Publishing Textbook of Substance Abuse Treatment, 4th Edition. ISBN 1585622761
^ Minozzi S, Amato L, Vecchi S, Davoli M, Kirchmayer U, Verster A (2011). "Oral naltrexone maintenance treatment for opioid dependence". Cochrane Database Syst Rev (4): CD001333. doi:10.1002/14651858.CD001333.pub4. PMID 21491383.
^ Hanson, Merideth (2001). "Three". In Alex Gitterman. The Handbook of Social Work practice with vulnerable and resilient populations, 2nd Edition (Second ed.). New York: Columbia University Press. |accessdate= requires |url= (help)
^ Hamilton RJ, Olmedo RE, Shah S, et al. (January 2002). "Complications of ultrarapid opioid detoxification with subcutaneous naltrexone pellets". Acad Emerg Med 9 (1): 63–8. doi:10.1111/j.1553-2712.2002.tb01169.x. PMID 11772672.
^ (2002), Rapid Opioid Detoxification in Australia. Academic Emergency Medicine, 9: 960–964.
^ ^a ^b Wodak, Dr. Alex (Summer 07/08). "I woke up cured of Naltrexone!" (Online Version of published magazine article). User's News (New South Wales User's and AIDS Association). Retrieved 2009-03-22. "Maybe there was an increased risk of death when people took naltrexone for a while and then started taking heroin? Maybe the success rate of naltrexone, whether started with UROR or ROD, was not as great as some had claimed?" Check date values in: |date= (help)
^ Simeon, Daphne. "An Open Trial of Naltrexone in the Treatment of Depersonalization Disorder". Journal of Clinical Psychopharmacology. Retrieved 2011-10-13.
^ ^a ^b Novella, Steven (5 May 2010). "Low Dose Naltrexone – Bogus or Cutting Edge Science?". Science-Based Medicine. Retrieved 5 July 2011.
^ Younger, Jarred (22 April 2009). "Fibromyalgia Symptoms are Reduced by Low-Dose Naltrexone: A Pilot Study". Science-Based Medicine. Retrieved 21 April 2014.
^ Bowling, Allen C. "Low-dose naltrexone (LDN) The "411" on LDN". National Multiple Sclerosis Society. Retrieved 6 July 2011.
^ King A, de Wit H, Riley R, Cao D, Niaura R, Hatsukami D (2006). "Efficacy of naltrexone in smoking cessation: A preliminary study and an examination of sex differences". Nicotine & Tobacco Research 8 (5): 671–82. doi:10.1080/14622200600789767. PMID 17008194.
^ Smith, Stanley G.; Gupta, Krishan K.; Smith, Sylvia H. (June 1995). "Effects of naltrexone on self-injury, stereotypy, and social behavior of adults with developmental disabilities". Journal of Developmental and Physical Disabilities 7 (2): 137–146. doi:10.1007/BF02684958.
^ Manley, Cynthia (1998-03-20). "Self-injuries may have biochemical base: study". The Reporter.
^ Grant, J (2009-04-03). "Drug Suppresses The Compulsion To Steal, Study Shows". Science daily.
^ "A randomized, double blind, placebo controlled trial of naltrexone in the treatment of concurrent alcohol dependence and pathological gambling"
^ Suck Won Kim, Jon E Grant, David E Adson, Young Chul Shin, Double-blind naltrexone and placebo comparison study in the treatment of pathological gambling, Biological Psychiatry, Volume 49, Issue 11, 1 June 2001, Pages 914-921.(http://www.sciencedirect.com/science/article/pii/S0006322301010794)
^ Bostwick, J. M. (2008-02-01). "Internet Sex Addiction Treated With Naltrexone". Mayo Clinic Proceedings.
^ Vignau J, Karila L, Costisella O, Canva V (2005). "[Hepatitis C, interferon a and depression: main physiopathologic hypothesis]". Encephale (in French) 31 (3): 349–57. doi:10.1016/s0013-7006(05)82400-5. PMID 16142050.
^ Małyszczak K, Inglot M, Pawłowski T, Czarnecki M, Rymer W, Kiejna A (2006). "[Neuropsychiatric symptoms related to interferon alpha]". Psychiatr. Pol. (in Polish) 40 (4): 787–97. PMID 17068950.
^ “Alcoholism Once A Month Injectable Drug, Vivitrol, Approved By FDA,” Medical News Today, April 16, 2006.
^ “Alkermes reclaims Vivitrol commercialization rights from Cephalon,” Mass High Tech, December 1, 2008.
^ Vivitrol Prescribing Information
^ James C. Garbutt, MD; Henry R. Kranzler, MD; Stephanie S. O’Malley, PhD; David R. Gastfriend, MD; Helen M. Pettinati, PhD; Bernard L. Silverman, MD; John W. Loewy, PhD; Elliot W. Ehrich, MD; “Efficacy and Tolerability of Long-Acting Injectable Naltrexone for Alcohol DependenceA Randomized Controlled Trial,” Journal of the American Medical Association, Vol. 293 No. 13, April 6, 2005.
^ “Alkermes Announces Positive Results from Phase 3 Clinical Study of Naltrexone for Extended-Release Injectable Suspension for the Treatment of Opioid Dependence”, Drugs.com November 16, 2009.
^ Krupitsky E, Nunes EV, Ling W, Illeperuma A, Gastfriend DR, Silverman BL (April 2011). "Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial". Lancet 377 (9776): 1506–13. doi:10.1016/S0140-6736(11)60358-9. PMID 21529928.
^ “FDA approves injectable drug to treat opioid-dependence patients,” U.S. Food and Drug Administration press announcement.
^ Nora D. Volkow, M.D, “Message from the Director on Important Treatment Advances for Addiction to Heroin and other Opiates,” National Institute on Drug Abuse, National Institutes of Health, October 2010.
^ Therapeutic Goods Administration. "Australian Register of Therapeutic Goods Medicines" (Online database of approved medicines). Retrieved 2009-03-22.
^ Hulse, Gary K.; Morris, Noella; Arnold-Reed, Diane; Tait, Robert J. (October 2009). "Improving Clinical Outcomes in Treating Heroin Dependence: Randomized, Controlled Trial of Oral or Implant Naltrexone". Archives of General Psychiatry 66 (10): 1108–1115. doi:10.1001/archgenpsychiatry.2009.130. PMID 19805701.
^ Pfohl DN, Allen JI, Atkinson, RL, et al: Naltrexone hydrochloride (Trexan): a review of serum transaminase elevations at high dosage. Reports of false-positive urinalysis results were found for the following formulary and nonprescription medications brompheniramine, bupropion, chlorpromazine, clomipramine, dextromethorphan, diphenhydramine, doxylamine, ibuprofen, naproxen, promethazine, quetiapine, quinolones (ofloxacin and gatifloxacin), ranitidine, sertraline, thioridazine, trazodone, venlafaxine, verapamil, and a nonprescription nasal inhaler. False-positive urinalysis results for amphetamine and methamphetamine were the most commonly reported. Problems of Drug Dependence, 1985 (NIDA Research Monograph 67). Edited by Harris LS. Washington, DC, U.S. Government Printing Office, 1986, pp 66–72
^ "Rs1799971 (SNPedia)".
^ HR Kranzler et al (2001). "Efficacy of Naltrexone and Acamprosate for Alcoholism Treatment: A Meta‐Analysis". Alcoholism: Clinical and Experimental Research.
^ Laura A. Ray, David W. Oslin (2009). "Naltrexone for the treatment of alcohol dependence among African Americans: Results from the COMBINE Study". Drug and Alcohol Dependence. doi:10.1016/j.drugalcdep.2009.07.006.
^ Laura A. Ray et al (March 2012). "The Role of the Asn40Asp Polymorphism of the Mu Opioid Receptor Gene (OPRM1) on Alcoholism Etiology and Treatment: A Critical Review". Alcohol Clin Exp Res. PMC 3249007.
^ Shader RI (August 2003). "Antagonists, Inverse Agonists, and Protagonists."Journal of Clinical Psychopharmacology". 2003 Aug; 23 (4): 321–322. doi:10.1097/01.jcp.0000087502.38434.6c. PMID 12920405. Cite uses deprecated parameters (help)
^ Haber, H.; Roske, I.; Rottmann, M.; Georgi, M.; Melzig, M. F. (1997). "Alcohol induces formation of morphine precursors in the striatum of rats". Life Sciences 60 (2): 79–89. doi:10.1016/S0024-3205(96)00597-8. PMID 9000113. edit

External links

LDNscience.org, a website dedicated to promoting and studying the therapeutic indications of low dose naltrexone.

UpToDate Contents

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1. アルコール使用障害に対する薬物療法 pharmacotherapy for alcohol use disorder
2. オピオイドの乱用および依存の治療 treatment of opioid abuse and dependence
3. 離人症性・現実感喪失性障害の治療 treatment of depersonalization derealization disorder
4. オピオイド系薬剤を慢性的に使用している患者における急性疼痛マネージメント management of acute pain in the patient chronically using opioids
5. 物質使用障害および不安関連障害を併発した場合の治療 treatment of co occurring substance use disorder and anxiety related disorders

English Journal

An evaluation of hepatic enzyme elevations among HIV-infected released prisoners enrolled in two randomized placebo-controlled trials of extended release naltrexone.

Vagenas P1, Di Paola A1, Herme M1, Lincoln T2, Skiest DJ2, Altice FL3, Springer SA4.
Journal of substance abuse treatment.J Subst Abuse Treat.2014 Jul;47(1):35-40. doi: 10.1016/j.jsat.2014.02.008. Epub 2014 Mar 12.
Extended-release naltrexone (XR-NTX), an approved treatment for opioid or alcohol dependence, is a once-monthly injectable formulation of naltrexone. Hepatotoxicity concerns have limited its use, necessitating further investigation. This study aims to examine hepatic enzyme levels in participants of
PMID 24674234

Naltrexone-loaded poly[La-(Glc-Leu)] polymeric microspheres for the treatment of alcohol dependence: in vitro characterization and in vivo biocompatibility assessment.

Pagar KP1, Vavia PR.
Pharmaceutical development and technology.Pharm Dev Technol.2014 Jun;19(4):385-94. doi: 10.3109/10837450.2013.784334. Epub 2013 Apr 16.
The poly[La-(Glc-Leu)] copolymer was applied in the present investigation as polymeric carrier to fabricate naltrexone (NTX)-loaded poly[La-(Glc-Leu)] microspheres in the single emulsion solvent evaporation technique for the long-term treatment of alcohol dependence. Newly synthesized poly[La-(Glc-L
PMID 23590187

Ex vivo studies for the passive transdermal delivery of low-dose naltrexone from a cream; detection of naltrexone and its active metabolite, 6β-naltrexol, using a novel LC Q-ToF MS assay.

Dodou K1, Armstrong A, Kelly I, Wilkinson S, Carr K, Shattock P, Whiteley P.
Pharmaceutical development and technology.Pharm Dev Technol.2014 May 2. [Epub ahead of print]
Abstract Naltrexone (NTX) is a long-acting opiate antagonist. Low-dose naltrexone (LDN) therapy has shown promising results in the treatment of several autoimmune disorders. Our aim was to formulate NTX into a cream for the delivery of LDN and develop an analytical technique for the quantification o
PMID 24785567

Japanese Journal

アルコール依存症の治療--薬物療法を中心として (特集アルコール依存症の展開)

松下幸生
日本精神科病院協会雑誌 30(4), 329-334, 2011-04-00
NAID 40018810809

Pharmacological Characterization of Itch-Associated Response Induced by Repeated Application of Oxazolone in Mice

Tsukumo Yukihito,Harada Daisuke,Manabe Haruhiko
Journal of pharmacological sciences 113(3), 255-262, 2010-07-20
… Both severe and continuous scratching behaviors were suppressed by the opioid-receptor antagonist naltrexone, but not by the H<SUB>1</SUB> …
NAID 10029889358

Scratching Behavior of ICR-Derived Glomerulonephritis (ICGN) Mice

Miyamoto Yohei,Umeuchi Hideo,Kurokawa Takahiro [他],NAKAO Kaoru,OKANO Kiyoshi
日本獣醫學会会誌 72(9), 1243-1245, 2010
… Furthermore, the scratching may have reflected a pruritus associated with renal dysfunction because it was inhibited by an opioid antagonist, naltrexone (3 mg/kg), effective against pruritus in hemodialysis patients. …
NAID 130000264228

Related Pictures

★リンクテーブル★

リンク元	「オピオイド」「ナルトレキソン」「ナルトレクソン」
拡張検索	「naltrexone hydrochloride」

「オピオイド」

Naltrexone
Systematic (IUPAC) name
	17-(cyclopropylmethyl)-4,5α-epoxy- 3,14-dihydroxymorphinan-6-one
Clinical data
Trade names	Revia
AHFS/Drugs.com	monograph
MedlinePlus	a685041
Pregnancy cat.	B3 (AU) C (US)
Legal status	Prescription Only (S4) (AU) ℞-only (CA) POM (UK) ℞-only (US)
Routes	Oral, intramuscular
Pharmacokinetic data
Bioavailability	5–40%
Protein binding	21%
Metabolism	hepatic
Half-life	4 h (naltrexone),; 13 h (6-β-naltrexol)
Excretion	Urine
Identifiers
CAS number	16590-41-3
ATC code	N07BB04
PubChem	CID 5360515
IUPHAR ligand	1639
DrugBank	DB00704
ChemSpider	4514524
UNII	5S6W795CQM
KEGG	D05113
ChEBI	CHEBI:7465
ChEMBL	CHEMBL19019
Chemical data
Formula	C20H23NO4
Mol. mass	341.401 g/mol
	SMILES O=C4[C@@H]5Oc1c2c(ccc1O)C[C@H]3N(CC[C@]25[C@@]3(O)CC4)CC6CC6;
	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 ; Key:DQCKKXVULJGBQN-XFWGSAIBSA-N ;
Physical data
Melt. point	169 °C (336 °F)
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英: opioid
同: 類麻薬
関: オピオイド受容体

オピオイド受容体に結合するモルフィン様物質のことを指す。

内因性のオピオイドペプチドが発見され、これらは内因性オピオイドペプチドと呼ばれるようになった。

作用

縮瞳

モルフィンと多くのμ,κアゴニストは瞳孔の縮小を引き起こす。これは瞳孔を支配する副交感神経の興奮による。μアゴニストを中毒量投与すると縮瞳し、pinpoints pupupilsはpathognomonicである。(GOO.559)