New paradigms and tools in drug design for pain and addiction

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

Research output: Chapter in Book/Report/Conference proceedingChapter

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 δ 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.

Original languageEnglish (US)
Title of host publicationDrug Addiction
Subtitle of host publicationFrom Basic Research to Therapy
PublisherSpringer New York
Pages477-494
Number of pages18
ISBN (Print)9780387766775
DOIs
StatePublished - Dec 1 2008

Keywords

  • GPCRs
  • bifunctional ligands
  • cholecystokinin receptors
  • drug design
  • neuropathic pain
  • opioid receptors
  • plasmon waveguide resonance spectroscopy

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)

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