The glycosylation of AGP and its associations with the binding to methadone.
Methadone remains the most common form of pharmacological therapy for opioid dependence; however, there is a lack of explanation for the reports of its relatively low success rate in achieving complete abstinence. One hypothesis is that in vivo binding of methadone to the plasma glycoprotein alpha-1-acid glycoprotein (AGP), to a degree dependent on the molecular structure, may render the drug inactive. This study sought to determine whether alterations present in the glycosylation pattern of AGP in patients undergoing various stages of methadone therapy (titration < two weeks, harm reduction < one year, long-term > one and a half years) could affect the affinity of the glycoprotein to bind methadone. The composition of AGP glycosylation was determined using high pH anion exchange chromatography (HPAEC) and intrinsic fluorescence analysed to determine the extent of binding to methadone. The monosaccharides galactose and N-acetyl-glucosamine were elevated in all methadone treatment groups indicating alterations in AGP glycosylation. AGP from all patients receiving methadone therapy exhibited a greater degree of binding than the normal population. This suggests that analysing the glycosylation of AGP in patients receiving methadone may aid in determining whether the therapy is likely to be effective.
School of Life, Sport and Social Sciences, Edinburgh Napier University, Sighthill Campus, Edinburgh, UK.
Jennifer L
JL
Behan
Yvonne E
YE
Cruickshank
Gerri
G
Matthews-Smith
Malcolm
M
Bruce
Kevin D
KD
Smith
D000117:Acetylglucosamine / Q000097:blood; D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000009:adverse effects*; D002852:Chromatography, Ion Exchange; D005260:Female; D005690:Galactose / Q000097:blood; D006023:Glycoproteins / Q000097:blood*; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D008297:Male; D008691:Methadone / Q000008:administration & dosage*; D011485:Protein Binding; D019966:Substance-Related Disorders / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome
D000701:Analgesics, Opioid; D006023:Glycoproteins; D008691:Methadone; D000117:Acetylglucosamine; D005690:Galactose