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 R Roeske, Todd W Vanderah, Josephine Lai

Research output: Contribution to journalArticle

21 Citations (Scopus)

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
JournalAAPS Journal
Volume8
Issue number3
DOIs
StatePublished - Jul 14 2006

Fingerprint

Drug Design
Substance-Related Disorders
Cholecystokinin Receptors
Pain
Narcotic Antagonists
Opioid Receptors
G-Protein-Coupled Receptors
Chronic Pain
Nervous System
Spectrum Analysis
Ligands
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Hruby, V. J., Porreca, F., Yamamura, H. I., Tollin, G., Agnes, R. S., Lee, Y. S., ... Lai, J. (2006). New paradigms and tools in drug design for pain and addiction. AAPS Journal, 8(3), [53]. https://doi.org/10.1208/aapsj080353

New paradigms and tools in drug design for pain and addiction. / Hruby, Victor J; Porreca, Frank; Yamamura, Henry I.; Tollin, Gordon; Agnes, Richard S.; Lee, Yeon Sun; Cai, Minying; Alves, Isabel; Cowell, Scott; Varga, Eva; Davis, Peg; Salamon, Zdzislaw; Roeske, William R; Vanderah, Todd W; Lai, Josephine.

In: AAPS Journal, Vol. 8, No. 3, 53, 14.07.2006.

Research output: Contribution to journalArticle

Hruby, VJ, Porreca, F, Yamamura, HI, Tollin, G, Agnes, RS, Lee, YS, Cai, M, Alves, I, Cowell, S, Varga, E, Davis, P, Salamon, Z, Roeske, WR, Vanderah, TW & Lai, J 2006, 'New paradigms and tools in drug design for pain and addiction', AAPS Journal, vol. 8, no. 3, 53. https://doi.org/10.1208/aapsj080353
Hruby, Victor J ; Porreca, Frank ; Yamamura, Henry I. ; Tollin, Gordon ; Agnes, Richard S. ; Lee, Yeon Sun ; Cai, Minying ; Alves, Isabel ; Cowell, Scott ; Varga, Eva ; Davis, Peg ; Salamon, Zdzislaw ; Roeske, William R ; Vanderah, Todd W ; Lai, Josephine. / New paradigms and tools in drug design for pain and addiction. In: AAPS Journal. 2006 ; Vol. 8, No. 3.
@article{94f95476cb164b49bd0384a07141e33e,
title = "New paradigms and tools in drug design for pain and addiction",
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.",
keywords = "Bifunctional ligands, Cholecyctokinin receptors, Drug design, GPCRs, Neuropathic pain, Opioid receptors, Plasmon waveguide resonance spectroscopy",
author = "Hruby, {Victor J} and Frank Porreca and Yamamura, {Henry I.} and Gordon Tollin and Agnes, {Richard S.} and Lee, {Yeon Sun} and Minying Cai and Isabel Alves and Scott Cowell and Eva Varga and Peg Davis and Zdzislaw Salamon and Roeske, {William R} and Vanderah, {Todd W} and Josephine Lai",
year = "2006",
month = "7",
day = "14",
doi = "10.1208/aapsj080353",
language = "English (US)",
volume = "8",
journal = "AAPS Journal",
issn = "1550-7416",
publisher = "Springer New York",
number = "3",

}

TY - JOUR

T1 - New paradigms and tools in drug design for pain and addiction

AU - Hruby, Victor J

AU - Porreca, Frank

AU - Yamamura, Henry I.

AU - Tollin, Gordon

AU - Agnes, Richard S.

AU - Lee, Yeon Sun

AU - Cai, Minying

AU - Alves, Isabel

AU - Cowell, Scott

AU - Varga, Eva

AU - Davis, Peg

AU - Salamon, Zdzislaw

AU - Roeske, William R

AU - Vanderah, Todd W

AU - Lai, Josephine

PY - 2006/7/14

Y1 - 2006/7/14

N2 - 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.

AB - 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.

KW - Bifunctional ligands

KW - Cholecyctokinin receptors

KW - Drug design

KW - GPCRs

KW - Neuropathic pain

KW - Opioid receptors

KW - Plasmon waveguide resonance spectroscopy

UR - http://www.scopus.com/inward/record.url?scp=33746446373&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33746446373&partnerID=8YFLogxK

U2 - 10.1208/aapsj080353

DO - 10.1208/aapsj080353

M3 - Article

VL - 8

JO - AAPS Journal

JF - AAPS Journal

SN - 1550-7416

IS - 3

M1 - 53

ER -