Brain penetration of methadone (R)- and (S)-enantiomers is greatly increased by P-glycoprotein deficiency in the blood?brain barrier of Abcb1a gene knockout mice
| العنوان: | Brain penetration of methadone (R)- and (S)-enantiomers is greatly increased by P-glycoprotein deficiency in the blood?brain barrier of Abcb1a gene knockout mice |
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| المؤلفون: | John S. Markowitz, C. Lindsay DeVane, Ying Ruan, Robin M. Taylor, Jennifer L. Donovan, Jun-Sheng Wang |
| المصدر: | Psychopharmacology. 173:132-138 |
| بيانات النشر: | Springer Science and Business Media LLC, 2004. |
| سنة النشر: | 2004 |
| مصطلحات موضوعية: | Male, Narcotics, Methadone maintenance, Pyrrolidines, Metabolite, Central nervous system, Biological Availability, Pharmacology, Blood–brain barrier, Mice, chemistry.chemical_compound, medicine, Animals, Tissue Distribution, ATP Binding Cassette Transporter, Subfamily B, Member 1, Chromatography, High Pressure Liquid, Gene knockout, P-glycoprotein, Mice, Knockout, biology, Biological Transport, medicine.anatomical_structure, chemistry, Blood-Brain Barrier, Area Under Curve, Knockout mouse, biology.protein, ATP-Binding Cassette Transporters, Methadone, medicine.drug |
| الوصف: | Methadone maintenance treatment is complicated by the wide variability of efficacy among patients. The large interindividual variability of the plasma concentrations of methadone was previously thought to be responsible for the variable therapeutic efficacy. However, recent studies suggested that methadone may be a substrate of P-glycoprotein (P-gp). Therefore, the function of P-gp in blood–brain barrier (BBB) may affect the concentration of methadone at its site(s) of action in the central nervous system, thereby contributing to its therapeutic efficacy and/or adverse events. To investigate the effect of P-gp on brain penetration of methadone (R)- and (S)-enantiomers and their major oxidative metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP). We compared the tissue distribution of methadone (R)- and (S)-enantiomers and EDDP in the Abcb1a−/− gene knockout mice and the Abcb1a+/+ wild-type mice 1 h following intraperitoneal administration of 15 μg Rac-methadone/g mouse. Plasma concentrations of (R)- and (S)-methadone were similar between the two animal groups. However, the brain concentrations of (R)- and (S)-methadone in the Abcb1a−/− mice were markedly higher (15- and 23-fold, respectively, P |
| تدمد: | 1432-2072 0033-3158 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::48f0f5b27b66df802bde578693bbcd27 https://doi.org/10.1007/s00213-003-1718-1 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....48f0f5b27b66df802bde578693bbcd27 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14322072 00333158 |
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