Genomes and Genes
Summary: A narcotic analgesic with a long onset and duration of action.
- Katchman A, McGroary K, Kilborn M, Kornick C, Manfredi P, Woosley R, et al. Influence of opioid agonists on cardiac human ether-a-go-go-related gene K(+) currents. J Pharmacol Exp Ther. 2002;303:688-94 pubmed
- Oliveto A, Farren C, Kosten T. Effect of LAAM dose on opiate use in opioid-dependent patients. A pilot study. Am J Addict. 1998;7:272-82 pubmed..22 +/- 0.08 and 0.53 +/- 0.12, under the high- and low-dose conditions, respectively (F = 11.8; P = 0.01). These results show that LAAM dose regimen affects the degree of abstinence from opioids. ..
- Eissenberg T, Stitzer M, Bigelow G, Buchhalter A, Walsh S. Relative potency of levo-alpha-acetylmethadol and methadone in humans under acute dosing conditions. J Pharmacol Exp Ther. 1999;289:936-45 pubmed
- Kuo I, Brady J, Butler C, Schwartz R, Brooner R, Vlahov D, et al. Feasibility of referring drug users from a needle exchange program into an addiction treatment program: experience with a mobile treatment van and LAAM maintenance. J Subst Abuse Treat. 2003;24:67-74 pubmed..0001). Although LAAM is no longer considered a first line treatment for heroin addiction, these results demonstrate the feasibility of utilizing long-acting agonist therapies such as LAAM to treat opioid dependence among NEP attenders. ..
- Jones H, Fitzgerald H, Johnson R. Males and females differ in response to opioid agonist medications. Am J Addict. 2005;14:223-33 pubmed..Within-subject change results indicate that all three medications benefit both sexes. Clinical trials should be designed to examine the impact of sex on outcomes. ..
- Lenne M, Dietze P, Rumbold G, Redman J, Triggs T. The effects of the opioid pharmacotherapies methadone, LAAM and buprenorphine, alone and in combination with alcohol, on simulated driving. Drug Alcohol Depend. 2003;72:271-8 pubmed..The findings are important in terms of the widespread implementation of these treatment options in Victoria given that a large proportion of pharmacotherapy clients drive. ..
- Cone E, Preston K. Toxicologic aspects of heroin substitution treatment. Ther Drug Monit. 2002;24:193-8 pubmed..Overall, the many recent developments in testing methodology provide more effective means to assess patients in heroin substitution programs and should contribute to improvements in public health. ..
- Hamilton K, Franklin L, Roy S, Schrott L. Prenatal opiate exposure attenuates LPS-induced fever in adult rats: role of interleukin-1beta. Brain Res. 2007;1133:92-9 pubmed..However, alterations in signaling mechanisms downstream from IL-1beta may play a role in the altered fever response in adult rats treated prenatally with opiates. ..
- Nekhayeva I, Nanovskaya T, Hankins G, Ahmed M. Role of human placental efflux transporter P-glycoprotein in the transfer of buprenorphine, levo-alpha-acetylmethadol, and paclitaxel. Am J Perinatol. 2006;23:423-30 pubmed..Therefore, it is reasonable to assume that the activity of P-gp could be one of the factors affecting the extent of fetal exposure to LAAM during pregnancy. ..
- Huang W, Bemis P, Slawson M, Moody D. Determination of l-alpha-acetylmethadol (LAAM), norLAAM, and dinorLAAM in clinical and in vitro samples using liquid chromatography with electrospray ionization and tandem mass spectrometry. J Pharm Sci. 2003;92:10-20 pubmed..An accurate and precise method for determination of LAAM and its metabolites, norLAAM and dinorLAAM, that is suitable for both in vivo and in vitro metabolism studies has been developed and validated. ..
- Oda Y, Kharasch E. Metabolism of methadone and levo-alpha-acetylmethadol (LAAM) by human intestinal cytochrome P450 3A4 (CYP3A4): potential contribution of intestinal metabolism to presystemic clearance and bioactivation. J Pharmacol Exp Ther. 2001;298:1021-32 pubmed
- Vaupel D, Jasinski D. l-alpha-Acetylmethadol, l-alpha-acetyl-N-normethadol and l-alpha-acetyl-N,N-dinormethadol: comparisons with morphine and methadone in suppression of the opioid withdrawal syndrome in the dog. J Pharmacol Exp Ther. 1997;283:833-42 pubmed..The usefulness of LAAM as a treatment for opiate addiction is likely due in part to the equivalent efficacies and higher potencies of its nor and dinor metabolites. ..
- Reid M, Angrist B, Baker S, O leary S, Stone J, Schwartz M, et al. A placebo controlled, double-blind study of mecamylamine treatment for cocaine dependence in patients enrolled in an opiate replacement program. Subst Abus. 2005;26:5-14 pubmed..05) and self-rated severity of cocaine dependence (p < 0.05) in the placebo group. This pilot study does not support the effectiveness of mecamylamine for the treatment of cocaine dependence in methadone or LAAM maintained patients. ..
- Gerak L, Galici R, France C. Self administration of cocaine in monkeys receiving LAAM acutely or chronically. Physiol Behav. 2008;93:20-6 pubmed..These studies indicated that LAAM administration did not attenuate the reinforcing effects of cocaine, suggesting that LAAM would not likely alter cocaine abuse in patients undergoing treatment for opioid abuse. ..
- Strathdee S, Ricketts E, Huettner S, Cornelius L, Bishai D, Havens J, et al. Facilitating entry into drug treatment among injection drug users referred from a needle exchange program: Results from a community-based behavioral intervention trial. Drug Alcohol Depend. 2006;83:225-32 pubmed..Such initiatives could be implemented at more than 140 needle exchange programs currently operating in the United States. These data also support the need for more accessible programs such as mobile or office-based drug abuse treatment. ..
- Ishøy T, Iversen C. [Substitutions therapy of opiate addiction in Denmark]. Ugeskr Laeger. 2003;165:3620-3 pubmed
- Morrish G, Foster D, Somogyi A. Differential in vitro inhibition of M3G and M6G formation from morphine by (R)- and (S)-methadone and structurally related opioids. Br J Clin Pharmacol. 2006;61:326-35 pubmed..These findings indicate a mechanism for reduced morphine clearance in methadone-maintained patients and reduced relative formation of the opioid active M6G compared with M3G. ..
- Eap C, Bouchoux G, Scherbaum N, Gastpar M, Powell Golay K, Baumann P. Determination of human plasma levels of levo-alpha-acetylmethadol and its metabolites by gas chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2004;805:141-6 pubmed..No interference was noted from methadone. This sensitive and specific analytical method could be useful for assessing the in vivo relationship between LAAM's blood levels, clinical efficacy and/or cardiotoxicity ..
- Kang J, Chen X, Wang H, Rampe D. Interactions of the narcotic l-alpha-acetylmethadol with human cardiac K+ channels. Eur J Pharmacol. 2003;458:25-9 pubmed
- Kleber H. Pharmacologic treatments for heroin and cocaine dependence. Am J Addict. 2003;12 Suppl 2:S5-S18 pubmed..In this paper, we discuss the use of medication in the context of general principles of opioid and cocaine addiction treatment. Both established medications and promising directions in pharmacotherapy will be addressed. ..
- Newcombe D, Bochner F, White J, Somogyi A. Evaluation of levo-alpha-acetylmethdol (LAAM) as an alternative treatment for methadone maintenance patients who regularly experience withdrawal: a pharmacokinetic and pharmacodynamic analysis. Drug Alcohol Depend. 2004;76:63-72 pubmed..LAAM converted methadone non-holders into LAAM holders. LAAM may therefore be useful in selected MMT non-holders and improve retention in opioid treatment programs. ..
- Kharasch E, Whittington D, Hoffer C, Krudys K, Craig K, Vicini P, et al. Paradoxical role of cytochrome P450 3A in the bioactivation and clinical effects of levo-alpha-acetylmethadol: importance of clinical investigations to validate in vitro drug metabolism studies. Clin Pharmacokinet. 2005;44:731-51 pubmed..These results highlight the need for clinical investigations to validate in vitro drug metabolism studies. ..
- Möllenhoff A, Nolte I, Kramer S. Anti-nociceptive efficacy of carprofen, levomethadone and buprenorphine for pain relief in cats following major orthopaedic surgery. J Vet Med A Physiol Pathol Clin Med. 2005;52:186-98 pubmed..For this reason, suitable methods must be found to improve analgesia, particularly in the immediate post-operative phase. ..
- Caplehorn J. Comments on Ritter et al.'s report of a comparative trial of LAAM and methadone maintenance. Addiction. 2004;99:509-10; author reply 510-1 pubmed
- Lintzeris N, Ritter A, Dunlop A, Muhleisen P. Training primary health care professionals to provide buprenorphine and LAAM treatment. Subst Abus. 2002;23:245-54 pubmed..Findings of the evaluation of these initiatives and the subsequent Australian postregistration training program for buprenorphine are described. ..
- Neff J, Moody D. Differential N-demethylation of l-alpha-acetylmethadol (LAAM) and norLAAM by cytochrome P450s 2B6, 2C18, and 3A4. Biochem Biophys Res Commun. 2001;284:751-6 pubmed..These studies show that the N-demethylation of LAAM and norLAAM is not restricted to P450 3A4, particularly P450s 2B6 and 2C18, and suggest that the mechanism of sequential metabolism for 3A4 differs from that of 2B6 and 2C18. ..
- Moody D, Alburges M, Parker R, Collins J, Strong J. The involvement of cytochrome P450 3A4 in the N-demethylation of L-alpha-acetylmethadol (LAAM), norLAAM, and methadone. Drug Metab Dispos. 1997;25:1347-53 pubmed..Knowledge of these enzymatic pathways is essential for assessment of the impact of metabolic drug-drug interactions on therapeutic success and/or adverse events...
- Sell S, McMahon L, Koek W, France C. Monoaminergic drugs and directly observable signs of LAAM withdrawal in rhesus monkeys. Behav Pharmacol. 2005;16:53-8 pubmed
- Newcombe D, Somogyi A, Bochner F, White J. Impaired psychomotor function and plasma methadone and levo-alpha-acetylmethadol (LAAM) concentrations in opioid-substitution patients. Exp Clin Psychopharmacol. 2017;25:223-233 pubmed publisher..These patients should be made aware that their ability to undertake complex tasks may be affected. (PsycINFO Database Record ..
- McCance Katz E, Rainey P, Smith P, Morse G, Friedland G, Gourevitch M, et al. Drug interactions between opioids and antiretroviral medications: interaction between methadone, LAAM, and nelfinavir. Am J Addict. 2004;13:163-80 pubmed..While no toxicities were observed, clinicians should be aware of the potential for drug interactions when patients require treatment with nelfinavir and these opiate medications. ..
- Deshmukh S, Nanovskaya T, Hankins G, Ahmed M. N-demethylation of levo-alpha-acetylmethadol by human placental aromatase. Biochem Pharmacol. 2004;67:885-92 pubmed..Taken together, the above data indicate that CYP 19/aromatase is the enzyme responsible for the N-demethylation of LAAM to norLAAM in term human placentas obtained from healthy pregnant women. ..
- Krantz M, Mehler P. Treating opioid dependence. Growing implications for primary care. Arch Intern Med. 2004;164:277-88 pubmed..Mainstreaming opioid addiction treatment has many advantages; its success will depend on resolution of ethical and delivery system issues as well as improved and expanded training of physicians in addiction medicine. ..
- Kreek M, Vocci F. History and current status of opioid maintenance treatments: blending conference session. J Subst Abuse Treat. 2002;23:93-105 pubmed..Future regulatory reform will likely involve the establishment of rules for "office based opioid treatment." ..
- Borg L, Ho A, Wells A, Joseph H, Appel P, Moody D, et al. The use of levo-alpha-acetylmethadol (LAAM) in methadone patients who have not achieved heroin abstinence. J Addict Dis. 2002;21:13-22 pubmed..While subject acceptance of LAAM was high, subjects were not in a "steady-state," with evidence of ongoing illicit opioid abuse. ..
- Armstrong S, Cozza K. Med-psych drug-drug interactions update. Psychosomatics. 2002;43:169-70 pubmed
- Moody D, Walsh S, Rollins D, Neff J, Huang W. Ketoconazole, a cytochrome P450 3A4 inhibitor, markedly increases concentrations of levo-acetyl-alpha-methadol in opioid-naive individuals. Clin Pharmacol Ther. 2004;76:154-66 pubmed
- Lesher G, Beierschmitt W. l-alpha-Acetylmethadol administration to lactating rat dams. Effect on hepatic aniline hydroxylase and ethylmorphine N-demethylase activities in rat pups. Drug Metab Dispos. 1988;16:9-14 pubmed..These changes, induced by LAAM administered via lactation, are reversible and do not interfere with the normal development of sex-dependent differences in hepatic EMDM activity observed in rats following sexual maturation. ..
- Freddi R, Duca P, Gritti I, Mariotti M, Vertemati M. Behavioral and degeneration changes in the basal forebrain systems of aged rats: a quantitative study in the region of the basal forebrain after levo-acetyl-carnitine treatments assessed by Abercrombie estimation. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33:419-26 pubmed publisher
- Wolstein J, Gastpar M, Finkbeiner T, Heinrich C, Heitkamp R, Poehlke T, et al. A randomized, open-label trial comparing methadone and Levo-Alpha-Acetylmethadol (LAAM) in maintenance treatment of opioid addiction. Pharmacopsychiatry. 2009;42:1-8 pubmed publisher..Our study confirmed the results of previous investigations with LAAM as being efficacious and well tolerated in opioid dependence. A discussion to reconsider the availability of LAAM is recommended. ..
- Johnson R, Chutuape M, Strain E, Walsh S, Stitzer M, Bigelow G. A comparison of levomethadyl acetate, buprenorphine, and methadone for opioid dependence. N Engl J Med. 2000;343:1290-7 pubmed..002). As compared with low-dose methadone, levomethadyl acetate, buprenorphine, and high-dose methadone substantially reduce the use of illicit opioids. ..
- Schuett H, Eipel C, Maletzki C, Menger M, Vollmar B. NO counterbalances HO-1 overexpression-induced acceleration of hepatocyte proliferation in mice. Lab Invest. 2007;87:602-12 pubmed..The present findings stress the role of NO to counterbalance vascular tone in HO-1 overexpressing animals for maintenance of adequate perfusion and salutary shear force within the hepatic microvasculature upon liver resection. ..
- Gowing L, Ali R, White J. Which substitution pharmacotherapy is most effective in treating opioid dependence?. Med J Aust. 2002;176:493-4 pubmed
- Schrott L, Sparber S. Suppressed fever and hypersensitivity responses in chicks prenatally exposed to opiates. Brain Behav Immun. 2004;18:515-25 pubmed..However, effects found in the chicks treated with 10 mg NLAAM/kg may have been partly related to the greater toxicity and/or protracted postnatal withdrawal in this group. ..
- Linehan M, Dimeff L, Reynolds S, Comtois K, Welch S, Heagerty P, et al. Dialectical behavior therapy versus comprehensive validation therapy plus 12-step for the treatment of opioid dependent women meeting criteria for borderline personality disorder. Drug Alcohol Depend. 2002;67:13-26 pubmed..A noteworthy secondary finding was that DBT participants were significantly more accurate in their self-report of opiate use than were those assigned to CVT + 12S. ..
- White J, Danz C, Kneebone J, La Vincente S, Newcombe D, Ali R. Relationship between LAAM-methadone preference and treatment outcomes. Drug Alcohol Depend. 2002;66:295-301 pubmed..For those who chose methadone, there were no differences in outcomes between the LAAM and methadone maintenance periods. Preference for LAAM is associated with treatment outcomes as good or better than those with methadone. ..
- Kinlock T, Battjes R, Schwartz R. A novel opioid maintenance program for prisoners: preliminary findings. J Subst Abuse Treat. 2002;22:141-7 pubmed..Nonetheless, study findings may also be applicable to methadone maintenance treatment, suggesting such treatment may be a promising means of engaging prisoners with preincarceration heroin dependence into continuing treatment. ..
- Maas B, Kerr T, Fairbairn N, Montaner J, Wood E. Pharmacokinetic interactions between HIV antiretroviral therapy and drugs used to treat opioid dependence. Expert Opin Drug Metab Toxicol. 2006;2:533-43 pubmed..This review was undertaken to summarise current knowledge on the interactions between the opioids and antiretrovirals and to make recommendations on the treatment of HIV-positive opioid-dependent patients. ..
- Schrott L, Franklin L, Serrano P. Prenatal opiate exposure impairs radial arm maze performance and reduces levels of BDNF precursor following training. Brain Res. 2008;1198:132-40 pubmed publisher..These data suggest that prenatal opiate exposure and/or postnatal withdrawal compromise expression of proteins involved in the neural plasticity underlying learning. ..
- Ling W, Rawson R, Compton M. Clinical treatment of opioid addiction and dependence. Methods Mol Med. 2003;84:285-95 pubmed
- Trafton J, Oliva E, Horst D, Minkel J, Humphreys K. Treatment needs associated with pain in substance use disorder patients: implications for concurrent treatment. Drug Alcohol Depend. 2004;73:23-31 pubmed..Pain complicates the treatment of SUD and should be addressed as an important co-morbidity during treatment. ..
- Kreek M. Methadone-related opioid agonist pharmacotherapy for heroin addiction. History, recent molecular and neurochemical research and future in mainstream medicine. Ann N Y Acad Sci. 2000;909:186-216 pubmed