Levomethadyl acetate

LAAM (L-a-acetylmethadol or levomethadyl acetate) is a full agonist at the i opioid receptor with pharmacologic properties similar to those of methadone. A number of studies have demonstrated that treatment with LAAM results in reduction of opioid use and beneficial effects comparable to those achieved with methadone (Ling et al. 1978 Tennant et al. 1986 Zangwell et al. 1986). However, retention rates are higher in patients who take methadone doses of 80—100 mg/day. 

Johnson RE, Chutuape MA, Strain EC, et al A comparison of levomethadyl acetate, buprenorphine, and methadone for opioid dependence. N EnglJ Med 343 1290-1297, 2000... 

Edwards G, Marshall EJ Cook CCH (2003). The Treatment of Drinking Problems A Guide for the Helping Professions, 4th ed. Cambridge Cambridge University Press Eissenberg T, Bigelow GE, Strain EC, Walsh SL, Brooner RK, Stitzer ML Johnson RE (1997). Dose-related efficacy of levomethadyl acetate for treatment of opioid dependence. Journal of the American Medical Association, 111, 1945-51... 

Scheme 5 Variations of methadone. Levomethadyl acetate, levomethadone ...

Opioid receptor binding Levomethadyl acetate has a moderate affinity for opioid receptors with selectivity for the p-type. Higher binding affinity is induced by the active metabolites /-alpha-nor-acetylmethadol, nor-methadol and methadol (Walczak et al., 1981 Carroll, 1976). 

Analgesic efficacy and clinical use Levomethadyl acetate, a methadone derivative, is a long-acting opioid analgesic, which is mostly used for the treatment of opioid dependence (Blaine etal., 1978 Ling, 1978)... 

Pharmacokinetic properties Levomethadyl acetate is well absorbed from the intestinal tract and is extensively metabolized to various active metabolites, which contribute to the long duration of action. The metabolites nor-acytylmethadol, di-nor-acetylmethadol, nor-methadol, and methadol are formed by N-demethylation and hydrolytic cleavage of the ester bond (Moody et al., 1997)... 

Side-effects Levomethadyl acetate induces opioid-type side-effects with respiratory depression, bradycardia and impairment of cardiac contractility (Wolven and Archer, 1976). The compound increases the QT-interval and may induce Torsade de pointes (Deamer et al., 2001). Because of the cardiovascular side effects (Q/T interval prolongation) Levomethadyl acetate was recently withdrawn from the market in most of the european countries. 

Deamer, R.L., Wilson, D.R., Clark, D.S., Prichard, J.G. Torsades de pointes associated with high dose levomethadyl acetate (ORLAAM), J. Addict. Dis. 2001, 20, 7-14. 

Alverine, azapropazone, benzhexol, diamphenethide, diethyltryptamine (-> yellow), dihydrocodeine, guai-phenesin, hordenine, levomethadyl acetate, normorphine, oxyphencyclimine, papaverine, terbutaline... 

Clomiphene, diethazine, levomethadyl acetate (— grey-green), methoxamine (- > green)... 

Gas Chromatography-Mass Spectrometry. In plasma, whole blood or tissues levomethadyl acetate and demethylated metabolites, sensitivity 5 ng/ml—T. A. Jennison et al., J. chromatogr. Sci., 1979, 17, 64-74. 

High Pressure Liquid Chromatography. In plasma or urine levomethadyl acetate and metabolites, sensitivity 6 ng/ml for levomethadyl acetate, L-a-noracetylmethadol and methadol, 10 ng/ml for L-a-dinoracetylmethadol, normethadol, and dinor-methadol—C.- H. Kiang et al., J. Chromat., 1981, 222 Biomed. AppL, 11, 81-93. 

After a single oral dose of 60 mg given to 5 subjects, peak plasma concentrations of 0.09 to 0.16 pg/ml (mean 0.13) of levomethadyl acetate and 0.04 to 0.05 pg/ml of L-a-noracetylmethadol were attained in about 2 to 4 hours and 2 to 6 hours, respectively following chronic oral treatment with 85 mg three times a week for three months to 3 subjects, peak plasma concentrations were levomethadyl acetate 0.16 to 0.23 pg/ml (mean 0.20), L-a-noracetylmethadol 0.15 to 0.30pg/ml (mean 0.24), and L-a-dinoracetylmethadol, mean 0.27 pg/ml (G. L. Henderson et al., Clin. Pharmac. Ther., 1977, 21, 16-25). 

The following postmortem tissue concentrations, pg/ml (mean, n), were reported in 9 heroin addicts who died unexpectedly during treatment with levomethadyl acetate ... 

Half-life. Plasma half-life, levomethadyl acetate about 50 hours, L-a-noracetylmethadol 30 to 65 hours, L-a-dinoracetylmethadol about 170 hours. 

Levomethadyl Acetate Hydro- Loperamide Hydrochloride Bromhexine Hydrochloride... 

Dimelor acetohexamide. dimenhydrinate diphenhydramine, dimepheptanol [ban, inn] (methadol NIH 2933) is one of the phenylpiperidine series, an OPIOID RECEPTOR AGONIST, which is active as an OPIOID ANALGESIC. It is also elaborated in a number of close analogues, derivatives or diastereoisomers with similar properties. These include methadyl acetate [ban, usan] = acetylmethadol [inn] alphamethadol (ban, inn] alphacetylmethadol [inn] levomethadyl levacetylmethadoi [inn] = levomethadyl acetate (usan) betamethadol [ban, usan) betacetylmethadol (inn) = betacemethadone. dimepropion [ban] (metamfepramone [inn]) is an ephedrine-like agent with SYMPATHOMIMETIC and CNS STIMULANT properties. It can be used as an appetite SUPPRESSANT. 

Levo-Dromoran levorphanol. levofenfluramine [inn) is the (/Q-form of fenfluramine hydrochloride. It is an (indirect-acting) SYMPATHOMIMETIC amine, levofloxacin ofloxacin, levoleucovorin calcium calcium levofolinale. levomenthol menthol, levomepromazine methotrimeprazine. levomethadone methadone, levomethadyl dimepheptanol. levomethadyl acetate dimepheptanol levacetylmethadol. 

---