2906 Naltrexone 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] 16590-41-3 5360515 C20H23NO4 341.162710 White powder. 168-170°C 100 mg/mL (as hydrochloride salt) Although well absorbed orally, naltrexone is subject to significant first pass metabolism with oral bioavailability estimates ranging from 5 to 40%. Naltrexone is a pure opiate antagonist and has little or no agonist activity. The mechanism of action of naltrexone in alcoholism is not understood; however, involvement of the endogenous opioid system is suggested by preclinical data. Naltrexone is thought to act as a competitive antagonist at mc, kappa, and delta receptors in the CNS, with the highest affintiy for the mu receptor. Naltrexone competitively binds to such receptors and may block the effects of endogenous opioids. This leads to the antagonization of most of the subjective and objective effects of opiates, including respiratory depression, miosis, euphoria, and drug craving. The major metabolite of naltrexone, 6-beta-naltrexol, is also an opiate antagonist and may contribute to the antagonistic activity of the drug. 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. Route of 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. Half Life: 4 hours for naltrexone and 13 hours for the active metabolite 6 beta-naltrexol. LD50: 1,100-1,550 mg/kg (oral, mouse) LD50: 1,450 mg/kg (oral, rat) LD50: 1,490 mg/kg (oral, guinea pig) No indication of carcinogenicity to humans (not listed by IARC). 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. Tolerance can develop, in which the person needs larger doses to achieve the desired effect; this can lead to overdose and death. Accidents or injury can also occur due to the side effects of loss of coordination, slowed reaction time, sleepiness and impaired judgment. Drugs in this category have a high potential for physical and psychological dependence. High doses of naltrexone (generally ≥1,000 mg/kg) produce salivation, depression/reduced activity, tremors, and convulsions. Patients should be treated symptomatically in a closely supervised environment. (L1712) 2009-07-21T20:27:27Z 2014-12-24T20:25:52Z Naltrexone C07253 7465 Naltrexone DB00704 true [H][C@@]12OC3=C(O)C=CC4=C3[C@@]11CCN(CC3CC3)[C@]([H])(C4)[C@]1(O)CCC2=O C20H23NO4 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 341.4009 341.162708229 Exogenous Solid 1.92 HMDB14842 CHEMBL19019 4514524 <p>Bao-Shan Huang, Yansong Lu, Ben-Yi Ji, Aris P Christodoulou, &#8220;Preparation of naltrexone from codeine and 3-benzylmorphine.&#8221; U.S. Patent US6013796, issued March, 1990.</p>