Testing for Inverse Agonism with Constitutive Receptor Systems

Terry Kenakin1

1 GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 9.5
DOI:  10.1002/0471141755.ph0905s32
Online Posting Date:  April, 2006
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This unit discusses the use of constitutive 7‐transmembrane/G protein coupled receptor (7TM/GPCR) activity for screening new drug entities. Following an introduction to constitutive 7TM/GPCR activity, the unit centers on the three basic components of a constitutive screening system: the receptor, the receptor coupling components (G protein), and the response reporting system. The design of specific assays to detect inverse agonism and the application of such systems to drug screening are also discussed. Finally, the relative advantages and disadvantages of inverse agonists as therapeutic agents are considered.

Keywords: constitutive; inverse agonist; neutral antagonist; G protein coupled receptors; orphan receptors; drug screening

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Table of Contents

  • GPCR Constitutive Activity
  • The Influence of Ligands on Constitutive GPCR Systems
  • Optimal Conditions for Constitutively Active Systems
  • Advantages and Disadvantages of Constitutively Active GPCR Assay Systems
  • Conclusions
  • Literature Cited
  • Figures
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Literature Cited

Literature Cited
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