The Effect of CYP2B6, CYP2D6, and CYP3A4 Alleles on Methadone Binding: A Molecular Docking Study
Current methadone maintenance therapy (MMT) is yet to ensure 100% successful treatment as the optimum dosage has yet to be determined. Overdose leads to death while lower dose causes the opioid withdrawal effect. Single-nucleotide polymorphisms (SNP) in cytochrome P450s (CYPs), the methadone metabol...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Hindawi Limited
2013-01-01
|
Series: | Journal of Chemistry |
Online Access: | http://dx.doi.org/10.1155/2013/249642 |
id |
doaj-72b2377fcde0410a9539490573a99156 |
---|---|
record_format |
Article |
spelling |
doaj-72b2377fcde0410a9539490573a991562020-11-24T22:49:59ZengHindawi LimitedJournal of Chemistry2090-90632090-90712013-01-01201310.1155/2013/249642249642The Effect of CYP2B6, CYP2D6, and CYP3A4 Alleles on Methadone Binding: A Molecular Docking StudyNik Nur Syazana Bt Nik Mohamed Kamal0Theam Soon Lim1Gee Jun Tye2Rusli Ismail3Yee Siew Choong4Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 11800 Minden, Penang, MalaysiaInstitute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 11800 Minden, Penang, MalaysiaInstitute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 11800 Minden, Penang, MalaysiaFaculty of Medicine, University of Malaya, 50603 Kuala Lumpur, MalaysiaInstitute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 11800 Minden, Penang, MalaysiaCurrent methadone maintenance therapy (MMT) is yet to ensure 100% successful treatment as the optimum dosage has yet to be determined. Overdose leads to death while lower dose causes the opioid withdrawal effect. Single-nucleotide polymorphisms (SNP) in cytochrome P450s (CYPs), the methadone metabolizers, have been showen to be the main factor for the interindividual variability of methadone clinical effects. In this study, we investigated the effect of SNPs in three major methadone metabolizers (CYP2B6, CYP2D6, and CYP3A4) on methadone binding affinity. Results showed that CYP2B6*11, CYP2B6*12, CYP2B6*18, and CYP3A4*12 have significantly higher binding affinity to R-methadone compared to wild type. S-methadone has higher binding affinity in CYP3A4*3, CYP3A4*11, and CYP3A4*12 compared to wild type. R-methadone was shown to be the active form of methadone; thus individuals with CYP alleles that binds better to R-methadone will have higher methadone metabolism rate. Therefore, a higher dosage of methadone is necessary to obtain the opiate effect compared to a normal individual and vice versa. These results provide an initial prediction on methadone metabolism rate for individuals with mutant type CYP which enables prescription of optimum methadone dosage for individuals with CYP alleles.http://dx.doi.org/10.1155/2013/249642 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nik Nur Syazana Bt Nik Mohamed Kamal Theam Soon Lim Gee Jun Tye Rusli Ismail Yee Siew Choong |
spellingShingle |
Nik Nur Syazana Bt Nik Mohamed Kamal Theam Soon Lim Gee Jun Tye Rusli Ismail Yee Siew Choong The Effect of CYP2B6, CYP2D6, and CYP3A4 Alleles on Methadone Binding: A Molecular Docking Study Journal of Chemistry |
author_facet |
Nik Nur Syazana Bt Nik Mohamed Kamal Theam Soon Lim Gee Jun Tye Rusli Ismail Yee Siew Choong |
author_sort |
Nik Nur Syazana Bt Nik Mohamed Kamal |
title |
The Effect of CYP2B6, CYP2D6, and CYP3A4 Alleles on Methadone Binding: A Molecular Docking Study |
title_short |
The Effect of CYP2B6, CYP2D6, and CYP3A4 Alleles on Methadone Binding: A Molecular Docking Study |
title_full |
The Effect of CYP2B6, CYP2D6, and CYP3A4 Alleles on Methadone Binding: A Molecular Docking Study |
title_fullStr |
The Effect of CYP2B6, CYP2D6, and CYP3A4 Alleles on Methadone Binding: A Molecular Docking Study |
title_full_unstemmed |
The Effect of CYP2B6, CYP2D6, and CYP3A4 Alleles on Methadone Binding: A Molecular Docking Study |
title_sort |
effect of cyp2b6, cyp2d6, and cyp3a4 alleles on methadone binding: a molecular docking study |
publisher |
Hindawi Limited |
series |
Journal of Chemistry |
issn |
2090-9063 2090-9071 |
publishDate |
2013-01-01 |
description |
Current methadone maintenance therapy (MMT) is yet to ensure 100% successful treatment as the optimum dosage has yet to be determined. Overdose leads to death while lower dose causes the opioid withdrawal effect. Single-nucleotide polymorphisms (SNP) in cytochrome P450s (CYPs), the methadone metabolizers, have been showen to be the main factor for the interindividual variability of methadone clinical effects. In this study, we investigated the effect of SNPs in three major methadone metabolizers (CYP2B6, CYP2D6, and CYP3A4) on methadone binding affinity. Results showed that CYP2B6*11, CYP2B6*12, CYP2B6*18, and CYP3A4*12 have significantly higher binding affinity to R-methadone compared to wild type. S-methadone has higher binding affinity in CYP3A4*3, CYP3A4*11, and CYP3A4*12 compared to wild type. R-methadone was shown to be the active form of methadone; thus individuals with CYP alleles that binds better to R-methadone will have higher methadone metabolism rate. Therefore, a higher dosage of methadone is necessary to obtain the opiate effect compared to a normal individual and vice versa. These results provide an initial prediction on methadone metabolism rate for individuals with mutant type CYP which enables prescription of optimum methadone dosage for individuals with CYP alleles. |
url |
http://dx.doi.org/10.1155/2013/249642 |
work_keys_str_mv |
AT niknursyazanabtnikmohamedkamal theeffectofcyp2b6cyp2d6andcyp3a4allelesonmethadonebindingamoleculardockingstudy AT theamsoonlim theeffectofcyp2b6cyp2d6andcyp3a4allelesonmethadonebindingamoleculardockingstudy AT geejuntye theeffectofcyp2b6cyp2d6andcyp3a4allelesonmethadonebindingamoleculardockingstudy AT rusliismail theeffectofcyp2b6cyp2d6andcyp3a4allelesonmethadonebindingamoleculardockingstudy AT yeesiewchoong theeffectofcyp2b6cyp2d6andcyp3a4allelesonmethadonebindingamoleculardockingstudy AT niknursyazanabtnikmohamedkamal effectofcyp2b6cyp2d6andcyp3a4allelesonmethadonebindingamoleculardockingstudy AT theamsoonlim effectofcyp2b6cyp2d6andcyp3a4allelesonmethadonebindingamoleculardockingstudy AT geejuntye effectofcyp2b6cyp2d6andcyp3a4allelesonmethadonebindingamoleculardockingstudy AT rusliismail effectofcyp2b6cyp2d6andcyp3a4allelesonmethadonebindingamoleculardockingstudy AT yeesiewchoong effectofcyp2b6cyp2d6andcyp3a4allelesonmethadonebindingamoleculardockingstudy |
_version_ |
1725674102056812544 |