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: Contribution to journalReview article

21 Scopus citations

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)
Article number53
Pages (from-to)E450-E460
JournalAAPS Journal
Volume8
Issue number3
DOIs
StatePublished - Jul 14 2006

Keywords

  • Bifunctional ligands
  • Cholecyctokinin receptors
  • Drug design
  • GPCRs
  • Neuropathic pain
  • Opioid receptors
  • Plasmon waveguide resonance spectroscopy

ASJC Scopus subject areas

  • Pharmaceutical Science

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  • Cite this

    Hruby, V. J., Porreca, F., Yamamura, H. I., Tollin, G., Agnes, R. S., Lee, Y. S., Cai, M., Alves, I., Cowell, S., Varga, E., Davis, P., Salamon, Z., Roeske, W., Vanderah, T., & Lai, J. (2006). New paradigms and tools in drug design for pain and addiction. AAPS Journal, 8(3), E450-E460. [53]. https://doi.org/10.1208/aapsj080353