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Methadone



Methadone Drug
Methadone is a synthetic opioid, used medically as an analgesic and in the treatment of narcotic addiction.


History


Methadone was first synthesized in 1937 by German scientists Max Bockmhl and Gustav Ehrhart at IG Farben (Hoechst-Am-Main) during their search for an analgesic that would be easier to use during surgery and also have low addiction potential. Methadone is a Schedule II drug under the Single Convention on Narcotic Drugs.

On September 11, 1941 Bockmhl and Ehrhart filed an application for a patent for a synthetic substance they called Hoechst 10820 or polamidon and whose structure had no relation to morphine or the opioid alkaloids (Bockmhl and Ehrhart, 1949). Although chemically unlike morphine or heroin, methadone also acts on the opioid receptors and thus produces many of the same effects. Chemically, methadone is the simplest of the opioids.

Methadone was introduced into the United States in 1947 by Eli Lilly and Company as an analgesic (They gave it the trade name Dolophine, which is now registered to Roxane Laboratories). Since then, it has been best known for its use in treating narcotic addiction, though it is also used in managing chronic pain due to its long duration of action and very low cost. In late 2004, the cost of a one month supply of methadone is 20 USD, as compared to an equivalent analgesic amount of Demerol at 120 USD. The old name Dolophine comes from the German Dolphium. The name derives from the Latin dolor (pain).

Methadone (as Dolophine) was first manufactured in the USA by Mallinckrodt pharmaceuticals, a St. Louis-based subsidiary of the Tyco International corporation. Mallinckrodt held the patent up until the early 1990s. Today a number of pharmaceutical companies produce and distribute methadone. However, the major producer remains Mallinckrodt. Mallinckrodt sells bulk methadone to most of the producers of generic preparations and also distributes its own brand name product in the form of tablets, dispersable tablets and oral concentrate under the name Methadose in the United States. Generally, one will only hear "dolophine" used by older addicts who used the product in the 1960s and 1970s. Medical professionals who believe that dolophine is the generic name for methadone, when actually it is the reverse, may also use the old brand name.

Pharmacology
Methadone has a slow metabolism and very high lipid solubility making it longer lasting than morphine-based drugs. Methadone has a typical half life of 24-48 hours, permitting the administration only once a day in heroin detoxification and maintenance programs. The most common mode of delivery at a Methadone clinic is in an oral solution. Methadone is almost as effective when administered orally as by injection. As with heroin, tolerance and dependence frequently develop. Current research in this area shows methadone has a unique affinity for the NMDA brain receptor. Some researchers propose that NMDA (N-methyl-D-aspartic acid) may regulate psychic dependence and tolerance by exhibiting opioid antagonist-like activity. Withdrawal symptoms are generally less acutely severe than those of morphine and heroin at equivalent doses, but are significantly more prolonged. Considered generally effective in management of heroin addiction and harm reduction (reduction of HIV rates, etc...). At proper dosing, it reduces the appetite for heroin. However, some heroin addicts feel that it is actually harder to quit methadone than heroin itself. Treatment at a methadone maintenance clinic is intended to be for an indefinite duration, as the treatment is not curative.

Clinical use
In recent years, Methadone has gained popularity among physicians for the treatment of chronic pain. The increased usage comes as doctors search for an opioid drug that can be dosed less frequently than short-acting drugs such as morphine or hydrocodone. Methadone, with its long half-life, oral bioavailability, and long duration of effect is a common second-choice drug for pain that doesn't respond to weaker agonists.

Abuse
Although not common, Methadone is encountered on the illicit drug market and has been associated with a number of overdose deaths. "Street Meth" demand comes primarily from opioid addicts unable to get into a legal methadone program; addicts seeking a high strongly prefer shorter-acting opioids. Studies have shown that the vast majority of methadone diverted to the illicit market comes from pain management prescriptions or theft from factories/shippers, not from maintenance patients.

Similar drugs
Closely related to methadone, the synthetic compound levo-alphacetylmethadol or LAAM (ORLAAM) has an even longer duration of action (from 48 to 72 hours), permitting a reduction in frequency of use. In 1994 it was approved as a treatment of narcotic addiction. Like methadone, LAAM is in Schedule II of the United States Controlled Substances Act. LAAM has since been removed from the US and European markets due to reports of rare cardiac side effects.

Buprenorphine has also been used in the treatment of narcotic addiction. In October, 2002, the FDA approved two compounds containing buprenorphine (Subutex and Suboxone) for the treatment of narcotic addiction. It is interesting to note that Subutex and Suboxone are in Schedule III of the United States Controlled Substances Act, which allows for their use on an outpatient basis, unlike methadone and LAAM. In the UK and many other countries, however, not only buprenorphine and methadone but also diamorphine (heroin) and other opioids are regularly used for outpatient treatment of opiate addiction, and treatment is generally provided in much less heavily regulated environments than in the United States. A recent study from Austria indicated that oral morphine provides better results than oral methadone, and studies of heroin maintenance have indicated that a low background dose of methadone combined with heroin maintenance may significantly improve outcomes for less-responsive patients.

Another close relative of methadone is dextropropoxyphene, first marketed in 1957 under the trade name of Darvon. Oral analgesic potency is one-half to one-third that of codeine, with 65 mg approximately equivalent to about 600 mg of aspirin. Dextropropoxyphene is prescribed for relief of mild to moderate pain. Bulk dextropropoxyphene is in Schedule II of the United States Controlled Substances Act, while preparations containing it are in Schedule IV. More than 100 tons of dextropropoxyphene are produced in the United States annually, and more than 25 million prescriptions are written for the products. This narcotic is associated with a number of toxic side effects and is among the top 10 drugs reported by medical examiners in recreational drug use deaths.

Other useful drug information: Zithromax | Vioxx | Fioricet | Ambien | Lamisil | Bactrim | Ranitidine

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