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German scientists synthesized methadone during World War II because of a shortage of morphine. Although chemically unlike morphine or heroin, methadone produces many of the same effects. It was introduced into the United States in 1947 as an analgesic (Dolophine?). Today, methadone is primarily used for the treatment of narcotic addiction, although a growing number of prescriptions are being written for chronic pain management. It is available in oral solutions, tablets, and injectable Schedule II formulations.
Methadone's effects can last up to 24 hours, thereby permitting once-a-day oral administration in heroin detoxification and maintenance programs. High-dose methadone can block the effects of heroin, thereby discouraging the continued use of heroin by addicts in treatment. Chronic administration of methadone results in the development of tolerance and dependence. The withdrawal syndrome develops more slowly and is less severe, but more prolonged than that associated with heroin withdrawal. Ironically, methadone used to control narcotic addiction is encountered on the illicit market. Recent increases in the use of methadone for pain management have been associated with increasing numbers of overdose deaths.
Closely related to methadone, the synthetic compound levo alphacetylmethadol, or LAAM (ORLMM?), has an even longer duration of action (from 48 to 72 hours) than methadone, permitting a reduction in frequency of use. In 1994, it was approved as a Schedule II treatment drug for narcotic addiction. Both methadone and LAAM have high abuse potential. Their acceptability as narcotic treatment drugs is predicated upon their ability to substitute for heroin, the long duration of action, and their mode of oral administration. Recent data regarding cardiovascular toxicity of LAAM has limited the use of this drug as a first-line therapy for addiction treatment.
This drug is a semi-synthetic narcotic derived from thebaine. Buprenorphine was initially marketed in the United States as an analgesic (Buprenex?). In 2002, two new products (Suboxone? and Subutex?) were approved for the treatment of narcotic addiction. Like methadone and LAAM, buprenorphine is potent (30 to 50 times the analgesic potency of morphine), has a long duration of action, and does not need to be injected. Unlike the other treatment drugs, buprenorphine produces far less respiratory depression and is thought to be safer in overdose. All buprenorphine products are currently in Schedule III of the CSA.
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