Related Experiment Video
Updated: Mar 9, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Neuroprotective Effects of a Structurally New Family of High Affinity Imidazoline I2 Receptor Ligands
Sònia Abás1, Amaia M Erdozain2,3, Benjamin Keller4
1Laboratory of Medicinal Chemistry (Associated Unit to CSIC), Department of Pharmacology, Toxicology and Medicinal Chemistry, Faculty of Pharmacy and Food Sciences, and Institute of Biomedicine (IBUB), University of Barcelona , Av. Joan XXIII 27-31, E-08028 Barcelona, Spain.
Abstract:
The imidazoline I2 receptors (I2-IRs) are widely distributed in the brain, and I2-IR ligands may have therapeutic potential as neuroprotective agents. Since structural data for I2-IR remains unknown, the discovery of selective I2-IR ligands devoid of α2-adrenoceptor (α2-AR) affinity is likely to provide valuable tools in defining the pharmacological characterization of these receptors. We report the pharmacological characterization of a new family of (2-imidazolin-4-yl)phosphonates. Radioligand binding studies showed that they displayed a higher affinity for I2-IRs than idazoxan, and high I2/α2 selectivity. In vivo studies in mice showed that acute treatments with 1b and 2c significantly increased p-FADD/FADD ratio (an index of cell survival) in the hippocampus when compared with vehicle-treated controls. Additionally, acute and repeated treatments with 2c, but not with 1b, markedly reduced hippocampal p35 cleavage into neurotoxic p25. The present results indicate a neuroprotective potential of (2-imidazolin-4-yl)phosphonates acting at I2-IRs.
More Related Videos
04:48A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate
Published on: July 10, 2018
09:39Drug-induced Sensitization of Adenylyl Cyclase: Assay Streamlining and Miniaturization for Small Molecule and siRNA Screening Applications
Published on: January 27, 2014
Related Concept Videos
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Ligand-gated Ion Channels
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that...
Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
Adrenergic Agonists: Indirect-Acting Agents
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral...
Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
The direct-acting...
Drugs Affecting Neurotransmitter Release or Uptake