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Narcotic Analgesics And Antagonists
Published in S.J. Mulé, Henry Brill, Chemical and Biological Aspects of Drug Dependence, 2019
The acetylmethadols, exemplified by Formula 24, are obtained by acetylation of the reduction products of methadone. The formation of a new asymmetric carbon atom leads to additional isomers. Alpha-i-acetylmethadol can be obtained by a lithium aluminum hydride reduction of d-methadone, and subsequent acetylation of the newly formed secondary alcohol; the prefix alpha referring to the predominant product obtained. Chemical reduction of methadones (via sodium in propanol) gives, predominantly, d-betamethadol.41
Delavirdine
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Delavirdine significantly decreased methadone clearance and increased the methadone elimination half-life, resulting in an increase in AUC of 19% and in Cmin of 29%. The combined effect of delavirdine on the total concentration of levo-alpha acetylmethadol (LAAM) and its active metabolites, norLAAM and dinorLAAM, was to significantly increase AUC by 43%, Cmax by 30%, and Cmin by 59% while decreasing time to maximum concentration (tmax) (McCance-Katz et al., 2006a). Delavirdine increased buprenorphine concentrations, but the effect was not considered clinically significant, and no alterations in buprenorphine effects in the volunteers being studies were seen (McCance-Katz et al., 2006a; McCance-Katz et al., 2006b).
Opioid Use Disorder
Published in James MacKillop, George A. Kenna, Lorenzo Leggio, Lara A. Ray, Integrating Psychological and Pharmacological Treatments for Addictive Disorders, 2017
Monica Bawor, Brittany Dennis, James MacKillop, Zainab Samaan
Previously, a formulation of levo-α-acetylmethadol (LAAM) was approved for the management of OUD in Canada and the United States. LAAM has been demonstrated superior to methadone for reducing illicit opioid use; however, this formulation had higher attrition rates than MMT [96]. LAAM was removed from market when demonstrated to increase risk for QT prolongation and cardiac arrhythmia in patients with OUD [97], and is not recommended.
The role of xenobiotic-metabolizing enzymes in the placenta: a growing research field
Published in Expert Review of Clinical Pharmacology, 2020
Ricardo Blanco-Castañeda, Carlos Galaviz-Hernández, Paula C. S. Souto, Victor Vitorino Lima, Fernanda R. Giachini, Carlos Escudero, Alicia E Damiano, L. Jazel Barragán-Zúñiga, Gerardo Martínez-Aguilar, Martha Sosa-Macías
In at term human placenta, the enzyme CYP19 is responsible for the metabolism of methadone to 2-ethylidine-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) [73], and of Levo-α-acetylmethadol (LAAM) to L-α-acetyl-N-normethadol (norLAAM) [123]. Methadone and EDDP have been identified in matched placenta and umbilical cord specimens from pregnant women receiving methadone daily [122,196]. However, placental EDDP appears to derive primarily from maternal methadone metabolism, since less than 1% of methadone is converted to EDDP in the placenta [197]. Infants born from mothers receiving methadone have presented lower birth weight, length, and head circumference [198].
Current and emerging pharmacotherapies for opioid dependence treatments in adults: a comprehensive update
Published in Expert Opinion on Pharmacotherapy, 2022
Jonna M. Leyrer-Jackson, Amanda M. Acuña, M. Foster Olive
Levo-alpha-acetylmethadol (LAAM), a full MOR agonist, was approved for OUD treatment in 1993, but was withdrawn from the market in 2004 [95,96] for reasons that are discussed below. However, given its promising effects while on the market, researchers continue to probe its efficacy and safety, as well as other structurally similar compounds. At the time when LAAM was under development, methadone was the only FDA approved medication for OUD. Since methadone was intended to be taken daily, LAAM was originally formulated to be taken 3 times a week to decrease the need for frequent clinic visits [95,97–99]. However, several issues emerged regarding LAAM that explain its short-lived clinical use. First, some clinics would require an initial period of methadone treatment before switching to LAAM, which led to problematic symptomology as patients adjusted to LAAM, potentially driving a preference for methadone. Further, patients who ceased using LAAM did so due to inadequate withdrawal relief, possibly as a result of inflexible dosing and a lack of availability of take-home formulations [99]. The most compelling issue with LAAM was that it produced cardiac symptomology in the form of arrhythmias which could lead to mortality, although rare. As a result of all of these concerns, the FDA changed LAAM’s status from front-line therapy to recommended use only when other therapies were unsuccessful, which was later followed by its discontinuation [97]. Since its discontinuation, researchers have reported that the cardiac symptoms observed in LAAM may not have been any worse than those observed with methadone [96]. Indeed, two comparison studies between methadone and LAAM showed no adverse cardiac events in patients using either drug, but similar or better retention of those taking LAAM as compared to those prescribed methadone. Additionally, both studies reported fewer opioid-positive urine tests upon follow-up with LAAM patients in comparison to those taking methadone. A shared observation by the authors of both studies is that the physicians overseeing patient care were able to adjust doses of LAAM based on patient characteristics, which is likely responsible for the observed positive outcomes [97,100]. Thus, while LAAM is not currently being utilized its formulation has shown promising results in the past and may prove beneficial if a reintroduction of the therapy were to be initiated.