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

Keywords

Related Articles

Opioid Tolerance Development: A Pharmacokinetic/Pharmacodynamic Perspective

The opioids are commonly used to treat acute and severe pain. Long-term opioid administration eventually reaches a dose ceiling that is attributable to the rapid onset of analgesic tolerance coupled with the slow develop...

Are Cutaneous Microdialysis Cytokine Findings Supported by End Point Biopsy Immunohistochemistry Findings?

Insertion of a cutaneous microdialysis catheter into normal dermis has been shown to induce the production of IL1b, IL6 and IL8 in an innate response to minimal trauma. In the present study, skin biopsy for immunohistoch...

Utilizing Internal Standard Responses to Assess Risk on Reporting Bioanalytical Results from Hemolyzed Samples

Bioanalytical analysis of toxicokinetic and pharmacokinetic samples is an integral part of small molecule drugs development and liquid chromatography—tandem mass spectrometry (LC-MS/MS) has been the technique of...

FDA Critical Path Initiatives: Opportunities for Generic Drug Development

FDA’s critical path initiative documents have focused on the challenges involved in the development of new drugs. Some of the focus areas identified apply equally to the production of generic drugs. However, ther...

Download PDF file
  • EP ID EP681800
  • DOI  10.1208/aapsj080353
  • Views 116
  • Downloads 0

How To Cite

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 (2006). New paradigms and tools in drug design for pain and addiction. The AAPS Journal, 8(3), -. https://www.europub.co.uk/articles/-A-681800