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. 2006 Jul 14;8(3):E450–E460. doi: 10.1208/aapsj080353

New paradigms and tools in drug design for pain and addiction

Victor J Hruby 1,3,✉, Frank Porreca 2, Henry I Yamamura 2, Gordon Tollin 1,3, Richard S Agnes 1, Yeon Sun Lee 1, Minying Cai 1, Isabel Alves 1,3, Scott Cowell 1, Eva Varga 2, Peg Davis 2, Zdzislaw Salamon 3, William Roeske 2, Todd Vanderah 2, Josephine Lai 2
PMCID: PMC1764851  NIHMSID: NIHMS13261  PMID: 17025262

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.

Keywords: drug design, neuropathic pain, bifunctional ligands, plasmon waveguide resonance spectroscopy, GPCRs, opioid receptors, cholecystokinin receptors

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