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 Concept Videos

Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

3.7K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
3.7K
Drug-Receptor Interaction: Agonist01:25

Drug-Receptor Interaction: Agonist

3.7K
Agonists are drugs that interact with specific receptors in the body to produce a biological response. When an agonist binds to a receptor, it activates or enhances the receptor's function, leading to physiological effects. The interaction between agonist drugs and receptors is crucial for their therapeutic action in various medical treatments.
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous...
3.7K
The Two-State Receptor Model01:29

The Two-State Receptor Model

3.0K
The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with...
3.0K
Drug-Receptor Interactions01:29

Drug-Receptor Interactions

7.2K
Drug-receptor interaction describes the binding of receptors by drugs, but not all drug-receptor interactions result in activation and tissue response. For instance, the binding of agonists activates the receptor to generate a cellular reaction, while antagonists bind to receptors without causing their activation.
Several parameters, such as the drug's affinity for its receptor and its efficacy, which is its ability to activate the receptor, determine the drug's effect on the tissue....
7.2K
Drugs Acting on Autonomic Ganglia: Stimulants01:23

Drugs Acting on Autonomic Ganglia: Stimulants

2.0K

Ganglionic stimulants activate NM nicotinic receptors in autonomic ganglia, falling into two categories: nicotine mimetics [e.g., lobeline, dimethylpiperazine, tetramethylammonium] and muscarinic receptor agonists [e.g., muscarine, methacholine]. The first category's action is rapid and blocked by nicotinic receptor antagonists, while the second category's action is delayed and blocked by atropine-like agents. Nicotine, an alkaloid, affects the heart rate by stimulating...
2.0K
Cholinergic Receptors: Nicotinic01:15

Cholinergic Receptors: Nicotinic

5.2K
Nicotinic receptors are ligand-gated ion channels that are activated by acetylcholine and nicotine. Upon activation, they cause a rapid increase in the permeability of cells to K+, Na+, and Ca2+, followed by depolarization and excitation. They are in the autonomic ganglia, skeletal neuromuscular junction, CNS, and adrenal medulla.
There are two types of nicotinic receptors: neuromuscular (NM/NM/N1) and neuronal (NN/NN/N2). The two families differ based on their location and selectivity to...
5.2K

You might also read

Related Articles

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

Sort by
Same author

Impact of body mass index on outcomes after radical cystectomy: A retrospective Australian cohort study.

BJUI compass·2026
Same author

A cannabidiol-sensitive region involved in the allosteric modulation of the α7 nicotinic receptor.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same author

Jet-induced rainfall seasonality and C<sub>4</sub> migration over East Asia.

Nature communications·2026
Same author

Author Correction: Salt and chronic kidney disease.

Nature reviews. Nephrology·2026
Same author

Salt and chronic kidney disease.

Nature reviews. Nephrology·2026
Same author

Ligand-driven modulation of chaperone-cochaperone networks shapes proteostasis outcomes.

Protein science : a publication of the Protein Society·2026

Related Experiment Video

Updated: Jan 8, 2026

Local Application of Drugs to Study Nicotinic Acetylcholine Receptor Function in Mouse Brain Slices
10:04

Local Application of Drugs to Study Nicotinic Acetylcholine Receptor Function in Mouse Brain Slices

Published on: October 29, 2012

19.8K

Understanding varenicline function via key receptor and ligand interactions.

Sheenagh G Aiken1, Daniele Fiorito1, Matthew Harper1

  • 1School of Chemistry, University of Bristol, Bristol BS8 1TS, UK.

Cell Reports. Physical Science
|December 22, 2025
PubMed
Summary

Varenicline, a smoking cessation drug, has unique interactions at the α4β2 nicotinic acetylcholine receptor (nAChR). Key residues like β2S133 are crucial for its function, revealing its distinct mechanism of action.

Keywords:
binding profilefunctional mutationsfunctional profileligand functionligand selectivitymolecular dynamics simulationsnicotinic acetylcholine receptorreceptor-agonist interactionsserotonin 5-HT receptor

More Related Videos

Live Imaging of Nicotine Induced Calcium Signaling and Neurotransmitter Release Along Ventral Hippocampal Axons
12:19

Live Imaging of Nicotine Induced Calcium Signaling and Neurotransmitter Release Along Ventral Hippocampal Axons

Published on: June 24, 2015

9.4K
Utilizing pHluorin-tagged Receptors to Monitor Subcellular Localization and Trafficking
09:59

Utilizing pHluorin-tagged Receptors to Monitor Subcellular Localization and Trafficking

Published on: March 16, 2017

9.3K

Related Experiment Videos

Last Updated: Jan 8, 2026

Local Application of Drugs to Study Nicotinic Acetylcholine Receptor Function in Mouse Brain Slices
10:04

Local Application of Drugs to Study Nicotinic Acetylcholine Receptor Function in Mouse Brain Slices

Published on: October 29, 2012

19.8K
Live Imaging of Nicotine Induced Calcium Signaling and Neurotransmitter Release Along Ventral Hippocampal Axons
12:19

Live Imaging of Nicotine Induced Calcium Signaling and Neurotransmitter Release Along Ventral Hippocampal Axons

Published on: June 24, 2015

9.4K
Utilizing pHluorin-tagged Receptors to Monitor Subcellular Localization and Trafficking
09:59

Utilizing pHluorin-tagged Receptors to Monitor Subcellular Localization and Trafficking

Published on: March 16, 2017

9.3K

Area of Science:

  • Pharmacology
  • Neuroscience
  • Molecular Biology

Background:

  • Varenicline, approved in 2006, is a first-in-class nicotinic-based smoking cessation therapy.
  • It targets the α4β2 nicotinic acetylcholine receptor (nAChR), but its precise molecular interactions remain unclear.
  • Understanding these interactions is key to explaining its clinical efficacy and distinguishing it from related compounds like nicotine and cytisine.

Purpose of the Study:

  • To elucidate the specific molecular interactions of varenicline at the α4β2 nAChR.
  • To identify key amino acid residues and structural features responsible for varenicline's unique pharmacological profile.
  • To deepen the understanding of varenicline's mechanism of action in smoking cessation.

Main Methods:

  • Multidisciplinary approach combining molecular and functional assays.
  • Site-directed mutagenesis to probe the role of specific binding-site residues (e.g., α4T139, α4T183, β2S133).
  • Analysis of novel varenicline variants to assess the importance of structural moieties like the quinoxaline group.

Main Results:

  • Identified specific binding-site residues (α4T139, α4T183, β2S133) as critical modulators of varenicline's function.
  • Demonstrated that substitution of β2S133 with valine significantly reduced varenicline's efficacy, highlighting its crucial role.
  • Found that the positioning of the quinoxaline moiety is essential for varenicline-mediated receptor activation.

Conclusions:

  • Varenicline exhibits a unique interaction network at the α4β2 nAChR, differentiating it from nicotine and cytisine.
  • Specific residues, particularly β2S133, and the quinoxaline moiety's placement are key determinants of varenicline's efficacy.
  • These findings provide a deeper molecular understanding of varenicline's mechanism of action for smoking cessation.