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

doi:10.1007/978-0-387-76678-2_28

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 proceeding › Chapter

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 language	English (US)
Title of host publication	Drug Addiction
Subtitle of host publication	From Basic Research to Therapy
Publisher	Springer New York
Pages	477-494
Number of pages	18
ISBN (Print)	9780387766775
DOIs	https://doi.org/10.1007/978-0-387-76678-2_28
State	Published - 2008

Keywords

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

ASJC Scopus subject areas

General Pharmacology, Toxicology and Pharmaceutics

Access to Document

10.1007/978-0-387-76678-2_28

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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. (2008). New paradigms and tools in drug design for pain and addiction. In Drug Addiction: From Basic Research to Therapy (pp. 477-494). Springer New York. https://doi.org/10.1007/978-0-387-76678-2_28

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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 = "GPCRs, bifunctional ligands, cholecystokinin receptors, drug design, 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 William Roeske and Todd Vanderah and Josephine Lai",

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doi = "10.1007/978-0-387-76678-2_28",

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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

AU - Vanderah, Todd

AU - Lai, Josephine

PY - 2008

Y1 - 2008

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 - GPCRs

KW - bifunctional ligands

KW - cholecystokinin receptors

KW - drug design

KW - neuropathic pain

KW - opioid receptors

KW - plasmon waveguide resonance spectroscopy

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BT - Drug Addiction

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ER -

New paradigms and tools in drug design for pain and addiction

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Keywords

ASJC Scopus subject areas

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