Acetyl methadol

Modification of the ketonic side chain is also consistent with retention of analgesic activity. Thus, reduction of methadone with lithium aluminum hydride affords the alcohol, 128 (apparently as a single diastereomer). Acetylation gives acetyl-methadol (129). ... 

Oda, Y., Kharasch, E. D., Metabolism of methadone and levo-a-acetyl-methadol (LAAM) by human intestinal cytochrome P450 3A4 (CYP3A4) potential contribution of intestinal metabolism to presystemic clearance and bioactivation, J. Pharmacol. Exp. Ther. 2001, 298, 1021-1032. 

A derivative of methadone, L-a-acetyl-methadol (LAAM) has been approved for the treatment of opioid addiction. In some addicts whose degree of tolerance is not known, the patient is first given methadone to stabilize the withdrawal signs and is then switched to LAAM. LAAM has an advantage over methadone in that it has a longer duration of action. Dosing is required only three times per week in most addicts to prevent withdrawal. 

There are not currently any medications that have been approved for treatment of MDMA addiction. In actuality, very few drugs of abuse have possible medical (pharmaceutical) treatments. Heroin addiction is one disease that is treatable by pharmaceutical means. Heroin addiction is often treated with methadone or levo-alpha-acetyl methadol (LAAM) administration. Similarly, alcohol addiction may be treated with pharmacological tools. However, most stimulants, such as cocaine, amphetamine, and MDMA, do not have medications available for treatment of addiction. 

Levo-alpha-acetyl methadol. A long-acting equivalent of methadone... 

Like methadone, LAAM (levo-alpha-acetyl-methadol) is a synthetic opiate used to treat heroin addiction. LAAM can block the effects of heroin for up to 72 hours. This makes outpatient treatment much more convenient, given that patients need to dose only two to three times a week. Naloxone and naltrexone are new medications that are also effective at blocking the pleasurable effects of heroin, helping motivated individuals to abstain. 

LAAM, the abbreviation of levo alpha acetyl methadol, is another opiate blocker that has been used to wean addicts. It persists up to 72 hours. 

These maintenance therapies supply regular doses of a drug that keeps the addict from experiencing withdrawal symptoms, drug cravings, or highs. Methadone and LAAM (levo-alpha-acetyl-methadol) are medications often used in these programs. 

Dimethylamino-4,4-diphenyl-3-heptanol (435.0 mg, 1.40 mmol) dissolved in ethyl acetate (10 ml) was treated with acetyl chloride (183.0 mg, 2.33 mmol). The mixture was refluxed for 2 h. After allowing the solution to cool to room temperature the solvent was removed under reduced pressure to leave a white foam, this crystallised from ethyl acetate to give 6-dimethylamino-4,4-diphenyl-3-acetoxyheptane hydrochloride (levo-a-acetyl methadol hydrochloride) (420.0 mg, 79%). 

Different substitution substances work for different periods of time, and this affects how they are administered. The longest-lasting substance is laevo-alpha-acetyl-methadol (LAAM), which can be taken as little as three times a week. Slow-release morphine can be given every other day, whereas methadone and MephenonR... 

Cumulative toxic effects such as motor depression, incipient coma, respiratory depression, severe nausea, vomiting, and mental confusion were observed following the subcutaneous administration of 30 mg. of dZ-a-acetyl-methadol twice daily for 2 days, and after 15 mg. of i-a-acetylmethadol twice daily for 3 days. Due to the long duration of action cumulative effects are obtained with multiple daily doses. 

Simultaneous Determination of Acetyl-methadol and Its Active Biotransformation Products in Human Biofluids... 

LAH reduces all three ketones and gives only one of the two possible diastereoisomeric alcohols designated the a-racemate in the cases of the branched chain ketones. The branched ketones give a//3 mixtures after treatment with sodium propanol from which the major (/3) isomer may be isolated. Similar results follow reduction of antipodal forms of methadone and isomethadone.(38) Both racemic methadols are inferior in potency to methadone (a, 0.08 yS, 0.2 methadone, 1) in the MHP test, but activity is more than restored on O-acetylation (a-acetate, 1.3 13-2). Racemic a-acety-... 

The acetylation of some primary aliphatic amines such as histamine. mescaline. and the bis-N-demethylated metabolite of of-j-methadol" "" also has been reported. In comparison with oxidative deamination processes. N-acetylation is only a minor pathway in the metabolism of this cla.ss of compounds. 

These compounds were recently developed (1952) and their pharmacology is incomplete. Reduction of d-methadone yields an a-methadol which is levorotatory. Acetyl-a-methadol is also levorotatory. Z-a-Meth-adol designates the levorotatory alcohol derived from d-methadone, and d-a-methadol the dextrorotatory alcohol derived from Z-methadone (92). Z-/3-Methadol designates the levorotatory alcohol from Z-methadone and d- -methadol the dextrorotatory alcohol from d-methadone. 

The a- and /3- racemic dZ-methadols are less effective than dZ-methadone the acetyl esters have toxicities similar to the parent compound, but produce more pronounced analgesia than does dZ-methadone (7). d-a-Afethadol and Z- -methadol were less effective than the parent compound Z-methadone. However, Z-a-methadol, Z-a-acetylmethadol, and d-/3 ac-etylmethadol exhibited analgesic activity when administered orally or subcutaneously these compounds are derived from d-methadone which has only slight analgesic activity (7). 

---