New paradigms and tools in drug design for pain and addiction
Journal Title: The AAPS Journal - Year 2006, Vol 8, Issue 3
Abstract
New modalities providing safe and effective treatment of pain, especially prolonged pathological pain, have not appeared despite much effort. In this mini-review/overview we suggest that new paradigms of drug design are required to counter the underlying changes that occur in the nervous system that may elicit chronic pain states. We illustrate this approach with the example of designing, in a single ligand, molecules that have agonist activity at μ and σ opioid receptors and antagonist activities at cholecystokinin (CCK) receptors. Our findings thus far provide evidence in support of this new approach to drug design. We also report on a new biophysical method, plasmon waveguide resonance (PWR) spectroscopy, which can provide new insights into information transduction in g-protein coupled receptors (GPCRs) as illustrated by the δ opioid receptor.
Authors and Affiliations
Victor J. Hruby, Frank Porreca, Henry I. Yamamura, Gordon Tollin, Richard S. Agnes, Yeon Sun Lee, Minying Cai, Isabel Alves, Scott Cowell, Eva Varga, Peg Davis, Zdzislaw Salamon, William Roeske, Todd Vanderah, Josephine Lai
Receptor-targeted gene delivery viafolate-conjugated polyethylenimine
A novel synthetic gene transfer vector was evaluated for tumor cell-specific targeted gene delivery. The folate receptor is a tumor marker overexpressed in more than 90% of ovarian carcinomas and large percentages of oth...
A Network Modeling Approach for the Spatial Distribution and Structure of Bone Mineral Content
This study aims to develop a spatial model of bone for quantitative assessments of bone mineral density and microarchitecture. A spatially structured network model for bone microarchitecture was systematically investigat...
Shrinkage in Nonlinear Mixed-Effects Population Models: Quantification, Influencing Factors, and Impact
The online version of this article (doi:10.1208/s12248-012-9407-9) contains supplementary material, which is available to authorized users.
Statistical Comparison of Dissolution Profiles to Predict the Bioequivalence of Extended Release Formulations
The online version of this article (doi:10.1208/s12248-014-9615-6) contains supplementary material, which is available to authorized users.
Challenges and Opportunities in Absorption, Distribution, Metabolism, and Excretion Studies of Therapeutic Biologics
With the advancement of biotechnology in the last two decades, optimized and novel modalities and platforms of biologic moieties have emerged rapidly in drug discovery pipelines. In addition, new technologies for deliver...