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 mu and delta 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 delta opioid receptor.
authors.affiliation: Department of Chemistry, University of Arizona, Tucson, AZ 85721, USA. hruby@u.arizona.edu
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Hruby
authors.forename: Frank
authors.initials: F
authors.lastname: Porreca
authors.forename: Henry I
authors.initials: HI
authors.lastname: Yamamura
authors.forename: Gordon
authors.initials: G
authors.lastname: Tollin
authors.forename: Richard S
authors.initials: RS
authors.lastname: Agnes
authors.forename: Yeon Sun
authors.initials: YS
authors.lastname: Lee
authors.forename: Minying
authors.initials: M
authors.lastname: Cai
authors.forename: Isabel
authors.initials: I
authors.lastname: Alves
authors.forename: Scott
authors.initials: S
authors.lastname: Cowell
authors.forename: Eva
authors.initials: E
authors.lastname: Varga
authors.forename: Peg
authors.initials: P
authors.lastname: Davis
authors.forename: Zdzislaw
authors.initials: Z
authors.lastname: Salamon
authors.forename: William
authors.initials: W
authors.lastname: Roeske
authors.forename: Todd
authors.initials: T
authors.lastname: Vanderah
authors.forename: Josephine
authors.initials: J
authors.lastname: Lai
mesh_terms: D016739:Behavior, Addictive / Q000188:drug therapy*; D015195:Drug Design; D018847:Opioid Peptides / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy*; D018710:Pain Clinics; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
chemical_list: D018847:Opioid Peptides; D043562:Receptors, G-Protein-Coupled