Taking the time to study competitive antagonism

Br J Pharmacol. 2007 Mar;150(5):541-51. doi: 10.1038/sj.bjp.0706997. Epub 2007 Jan 22.


Selective receptor antagonists are one of the most powerful resources in a pharmacologist's toolkit and are essential for the identification and classification of receptor subtypes and dissecting their roles in normal and abnormal body function. However, when the actions of antagonists are measured inappropriately and misleading results are reported, confusion and wrong interpretations ensue. This article gives a general overview of Schild analysis and the method of determining antagonist equilibrium constants. We demonstrate why this technique is preferable in the study of competitive receptor antagonism than the calculation of antagonist concentration that inhibit agonist-evoked responses by 50%. In addition we show how the use of Schild analysis can provide information on the outcome of single amino acid mutations in structure-function studies of receptors. Finally, we illustrate the need for caution when studying the effects of potent antagonists on synaptic transmission where the timescale of events under investigation is such that ligands and receptors never reach steady-state occupancy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Binding, Competitive*
  • Computer Simulation
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical / methods
  • Excitatory Amino Acid Agonists / metabolism
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / metabolism
  • Excitatory Amino Acid Antagonists / pharmacology
  • Humans
  • Ion Channel Gating / drug effects*
  • Ion Channels / agonists
  • Ion Channels / antagonists & inhibitors*
  • Ion Channels / genetics
  • Ion Channels / metabolism
  • Kinetics
  • Ligands*
  • Models, Biological
  • Nicotinic Agonists / metabolism
  • Nicotinic Agonists / pharmacology
  • Nicotinic Antagonists / metabolism
  • Nicotinic Antagonists / pharmacology
  • Point Mutation
  • Protein Binding
  • Receptors, Cell Surface / agonists
  • Receptors, Cell Surface / antagonists & inhibitors*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, Nicotinic / drug effects
  • Reproducibility of Results
  • Synaptic Transmission / drug effects


  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Ion Channels
  • Ligands
  • Nicotinic Agonists
  • Nicotinic Antagonists
  • Receptors, Cell Surface
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Nicotinic