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Journal Article
Research Support, Non-U.S. Gov't
Neuroprotective Effects of a Structurally New Family of High Affinity Imidazoline I 2 Receptor Ligands.
ACS Chemical Neuroscience 2017 April 20
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.
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