Naltrexone

개요This drug does not have agonistic properties. It is similar to naloxone in terms of pharmacological characteristics; however, it differs in two important ways—long-lasting action and that its metabolite 6-β-naltrexol is also a strong antagonist. Naltrexone is potentially hepatotoxic. Naltrexone is used for blocking pharmacological effects of opioids upon their overdose.

역사Naloxone was discovered by Drs. Jack Fischman and Mozez Lewenstein of the Memorial Sloan Kettering Institute for Cancer Research in 1961, based on a theory proposed by their colleague, Dr. Harold Blumberg at the Long Island-based Endo Laboratories. Intravenous naloxone (Envizio) was approved by the Food and Drug Administration (FDA) for opioid overdose reversal in 1971 and was shortly adopted as a standard emergency treatment at many of the nation’s premier academic medical centers.

역사Naltrexone was first synthesized in 1963 by Endo Laboratories, which was patented by Endo Laboratories in 1967 under the developmental code name EN-1639A. Naltrexone was later purchased in 1969 by DuPont Pharmaceuticals. It was developed by the National Institute on Drug Abuse in the 1970s and early 1980s . In 1984, it was approved by the Food and Drug Administration (FDA) for the treatment of heroin addiction . In 1995, Naltrexone was approved by the FDA for the treatment of alcoholism, when the brand name was changed by DuPont to Revia. A new extended-release formulation of naltrexone has been developed and was approved by the FDA in 2006 for use in the treatment of alcohol dependence.

용도Labeled Naltrexone, intended for use as an internal standard for the quantification of Naltrexone by GC- or LC-mass spectrometry.

일반 설명Naltrexone is a pure opioid antagonist at allopioid receptor subtypes with the highest affinity for theμ-receptor. Naltrexone is orally bioavailable and blocksthe effects of opiate agonists for approximately 24 hoursafter a single dose of 50 mg. It produces no opioid agonisteffects and is devoid of any intrinsic actions other thanopioid receptor blockade. Theoretically, it should workwell to treat opioid dependence but in clinical practice,patients have shown poor compliance and high relapserates. Naltrexone has also been studied to treat alcohol dependencewith mixed results. To address the complianceissues and effectively remove the “choice” of taking theantagonist, naltrexone was developed into an extendedreleaseinjectable microsphere formulation for IM injectiononce a month (Vivitrol). This formulation providessteady-state plasma concentrations of naltrexone threefoldto fourfold higher than the 50-mg oral dose 4 times aday. Currently, Vivitrol is only indicated for the treatmentof alcohol dependence. A Cochrane review found insufficientevidence from randomized controlled trials toevaluate its effectiveness for treating opioid dependence. Currently, phase II and phase III clinical trials ofan implantable pellet form of naltrexone are being conductedfor treating opioid dependence.The CYP450 system is not involved in naltrexonemetabolism. Naltrexone is reduced to the active antagonist6-β-naltrexol by dihydrodiol dehydrogenase, a cytosolicenzyme. Naltrexone has a black box warning, because ithas the potential to cause hepatocellular injury when givenin excessive doses.