2718 Methadone A synthetic opioid that is used as the hydrochloride. It is an opioid analgesic that is primarily a mu-opioid agonist. It has actions and uses similar to those of morphine. It also has a depressant action on the cough center and may be given to control intractable cough associated with terminal lung cancer. Methadone is also used as part of the treatment of dependence on opioid drugs, although prolonged use of methadone itself may result in dependence. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1082-3). In Australia methadone is a Schedule 8 (controlled) drug. 76-99-3 4095 C21H27NO 309.209260 Crystalline powder (MSDS A308) 235.0°C 5.90e-03 g/L Inhalation (MSDS, RxList, A308); dermal (MSDS, RxList, A308); ingestion (MSDS, RxList, A308); intravenous injection (MSDS, RxList, A308). Well absorbed following oral administration. The bioavailability of methadone ranges between 36 to 100%. Methadone is a mu-agonist; a synthetic opioid analgesic with multiple actions qualitatively similar to those of morphine, the most prominent of which involves the central nervous system and organs composed of smooth muscle. The principal therapeutic uses for methadone are for analgesia and for detoxification or maintenance in opioid addiction. The methadone abstinence syndrome, although qualitatively similar to that of morphine, differs in that the onset is slower, the course is more prolonged, and the symptoms are less severe. Some data also indicate that methadone acts as an antagonist at the N-methyl-D-aspartate (NMDA) receptor. The contribution of NMDA receptor antagonism to methadone's efficacy is unknown. Other NMDA receptor antagonists have been shown to produce neurotoxic effects in animals. Hepatic. Cytochrome P450 enzymes, primarily CYP3A4, CYP2B6, and CYP2C19 and to a lesser extent CYP2C9 and CYP2D6, are responsible for conversion of methadone to EDDP and other inactive metabolites, which are excreted mainly in the urine. Route of Elimination: The elimination of methadone is mediated by extensive biotransformation, followed by renal and fecal excretion. Unmetabolized methadone and its metabolites are excreted in urine to a variable degree. Half Life: 24-36 hours No indication of carcinogenicity to humans (not listed by IARC). For the treatment of dry cough, drug withdrawal syndrome, opioid type drug dependence, and pain (A308). Bradycardia and hypotension. In severe overdosage, particularly by the intravenous route, apnea, circulatory collapse, cardiac arrest, and death may occur (RxList, A308). Medical problems can include congested lungs, liver disease, tetanus, infection of the heart valves, skin abscesses, anemia and pneumonia. Death can occur from overdose. In severe overdosage, particularly by the intravenous route, apnea, circulatory collapse, cardiac arrest, and death may occur. Primary attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled ventilation. If a non-tolerant person, takes a large dose of methadone, effective opioid antagonists are available to counteract the potentially lethal respiratory depression. (L1712) 2009-07-15T20:47:26Z 2014-12-24T20:25:49Z Cytochrome P450 2C19 (CYP2C19) (P33261) (A308) Cytochrome P450 3A4 (CYP3A4) (P08684) (A308) Cytochrome P450 2B6 (CYP2B6) (P20813) (A308). Methadone C07163 6807 Methadone DB00333 true Cytochrome P450 2C19 (P33261) Cytochrome P450 3A4 (P08684) Cytochrome P450 2B6 (P20813) (A308) CCC(=O)C(CC(C)N(C)C)(C1=CC=CC=C1)C1=CC=CC=C1 C21H27NO InChI=1/C21H27NO/c1-5-20(23)21(16-17(2)22(3)4,18-12-8-6-9-13-18)19-14-10-7-11-15-19/h6-15,17H,5,16H2,1-4H3 InChIKey=USSIQXCVUWKGNF-UHFFFAOYNA-N 309.4452 309.209264491 Exogenous Solid 3.93 HMDB14477 CHEMBL651 3953 <p>Charles J. Barnett, &#8220;Modification of methadone synthesis process step.&#8221; U.S. Patent US4048211, issued August, 1952.</p>