Calculation of agonist efficacy, apparent affinity, and receptor population changes after administration of insurmountable antagonists: Comparison of different analytical approaches

Gerald Zernig, Tom Issaevitch, James H. Woods

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

The determination of the affinity and efficacy of an agonist in functional (as opposed to radioligand binding) experiments is necessary to explain its potency. Using modeled dose-response data both in their ideal form and with an added average deviation as well as previously published experimental data, a variety of analytical approaches were compared which differed in goodness-of-fit, ease of handling, and range of successful application. A nonlinear curve-fitting algorithm that analyzed several dose-response curves simultaneously and fitted them to an extended version of the operational model of Black and Leff (1983) (Proc R Soc Lond B 220:141-162) was demonstrated to be superior to the other approaches using the above criteria. However, judging from the limitations of the analytical approaches, claims of efficacy or affinity differences between agonists that are based on less than 10-fold numerical differences in the same behavioral paradigm should be viewed with skepticism. Et was also found that simple inspection of dose-response curves obtained before and after administration of an insurmountable antagonist give estimates of fair accuracy under most circumstances.

Original languageEnglish (US)
Pages (from-to)223-237
Number of pages15
JournalJournal of Pharmacological and Toxicological Methods
Volume35
Issue number4
DOIs
StatePublished - Aug 1996
Externally publishedYes

Keywords

  • Alfentanil
  • Analgesia
  • Antinociception
  • Apparent in vivo affinity
  • Efficacy
  • Modeling
  • Morphine
  • Operational model
  • Opioids
  • Receptor reserve
  • Spare receptors

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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