Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

A four-ligand hypercube model to quantify allosteric interactions within the GABAA receptor complex.

Clementina M van Rijn1, Elly Willems-van Bree

  • 1NICI/Department of Biological Psychology, University of Nijmegen, Post-box 9104, 6500 HE Nijmegen, The Netherlands. rijn@nici.kun.nl

European Journal of Pharmacology
|February 6, 2004
PubMed
Summary

This study reveals synergistic interactions between GABA, a neuroactive steroid, and retigabine at GABA(A) receptor sites. These allosteric couplings enhance drug efficacy, offering insights into polytherapy and variable drug responses.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Rethinking Mechanical Ventilation: Can Ventilation Mode Influence Long-Term Cognitive Outcomes in ICU Patients with COVID-19?

Journal of clinical medicine·2026
Same author

Negative Pressure Ventilation Can Prevent Ventilator-associated Brain Injury.

American journal of respiratory and critical care medicine·2024
Same author

Negative pressure ventilation, an umbrella against ventilator induced lung injury.

Intensive care medicine·2024
Same author

Network analysis reveals a role of the hippocampus in absence seizures: The effects of a cannabinoid agonist.

Epilepsy research·2023
Same author

Perioperative Pulmonary Atelectasis: Comment.

Anesthesiology·2022
Same author

The interaction between pain and cognition: on the roles of task complexity and pain intensity.

Scandinavian journal of pain·2021

Area of Science:

  • Neuroscience
  • Pharmacology
  • Biochemistry

Background:

  • The GABA(A) receptor complex is a key target for various neuroactive compounds.
  • Understanding allosteric modulations is crucial for developing effective therapeutic strategies.

Purpose of the Study:

  • To investigate the allosteric couplings between binding sites on the GABA(A) receptor complex.
  • To examine the combined effects of GABA, a neuroactive steroid (Org 20549), and an antiepileptic drug (retigabine).

Main Methods:

  • Receptor-binding assays using rat brain membranes and [3H]TBOB as a tracer ligand.
  • Isobolic analysis to evaluate synergistic interactions between the three test compounds.
  • Application of a hypercube model to quantify allosteric interactions.

Related Experiment Videos

Main Results:

  • GABA, Org 20549, and retigabine all inhibited [3H]TBOB binding, with EC(50) values of 4.0, 98, and 23 microM, respectively.
  • Isobolic analysis demonstrated synergistic interactions among the three compounds in displacing [3H]TBOB.
  • A hypercube model quantified these allosteric couplings, showing enhanced affinity with simultaneous ligand binding.

Conclusions:

  • The three compounds bind to different, allosterically coupled sites on the GABA(A) receptor.
  • Synergistic interactions suggest potential for enhanced therapeutic effects in polytherapy.
  • Findings may explain individual variability in drug responses and inform rational polypharmacy.