The Interaction of Fatty Acid Amide Hydrolase (FAAH) Inhibitors with an Anandamide Carrier Protein Using 19F-NMR
Journal Title: The AAPS Journal - Year 2013, Vol 15, Issue 2
Abstract
It has been reported that the endocannabinoid anandamide (AEA) binds to a class of fatty acid-binding proteins and serum albumin which can serve as carrier proteins and potentiate the cellular uptake of AEA and its intracellular translocation. Here, we employed 19F nuclear magnetic resonance spectroscopy to study the interactions of serum albumin with two inhibitors of fatty acid amide hydrolase (FAAH), the enzyme involved in the deactivation of anandamide. We found that, for both inhibitors AM5206 and AM5207, the primary binding site on serum albumin is drug site 1 located at subdomain IIA. Neither inhibitor binds to drug site 2. While AM5207 binds exclusively to drug site 1, AM5206 also interacts with other fatty acid-binding sites on serum albumin. Additionally, AM5206 has an affinity for serum albumin approximately one order of magnitude higher than that of AM5207. The data suggest that interactions of FAAH inhibitors with albumin may provide added advantages for their ability to modulate endocannabinoid levels for a range of applications including analgesia, antiemesis, and neuroprotection.
Authors and Affiliations
Jianqin Zhuang, De-Ping Yang, Spyros P. Nikas, Jianhong Zhao, Jianxin Guo, Alexandros Makriyannis
Keywords
Related Articles
- EP ID EP681099
- DOI 10.1208/s12248-013-9455-9
- Views 65
- Downloads 0
Use of Different Parameters and Equations for Calculation of IC50 Values in Efflux Assays: Potential Sources of Variability in IC50 Determination
The online version of this article (doi:10.1208/s12248-013-9554-7) contains supplementary material, which is available to authorized users.
An automated process for building reliable and optimal in vitro/in vivo correlation models based on Monte Carlo simulations
Many mathematical models have been proposed for establishing an in vitro/in vivo correlation (IVIVC). The traditional IVIVC model building process consists of 5 steps: deconvolution, model fitting, convolution, predictio...
A Mass Balance-Based Semiparametric Approach to Evaluate Neonatal Erythropoiesis
Postnatal hemoglobin (Hb) production in anemic preterm infants is determined by several factors including the endogenous erythropoietin levels, allogeneic RBC transfusions administered to treat anemia, and developmental...
Preparation and ocular pharmacokinetics of ganciclovir liposomes
Ophthalmic liposomes of ganciclovir (GCV) were prepared by the reverse phase evaporation method, and their ocular pharmacokinetics in albino rabbits were compared with those obtained after dosing with GCV solution. The i...
Supersaturated Self-Nanoemulsifying Drug Delivery Systems (Super-SNEDDS) Enhance the Bioavailability of the Poorly Water-Soluble Drug Simvastatin in Dogs
This study investigates the potential of supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) to improve the bioavailability of poorly water-soluble drugs compared to conventional SNEDDS. Conventional...