Developing New 4-PIOL and 4-PHP Analogues for Photoinactivation of γ-Aminobutyric Acid Type A Receptors.

The critical roles played by GABA receptors as inhibitory regulators of excitation in the central nervous system has been known for many years. Aberrant GABA receptor function and trafficking deficits have also been associated with several diseases including anxiety, depression, epilepsy, and insomnia. As a consequence, important drug groups such as the benzodiazepines, barbiturates, and many general anesthetics have become established as modulators of GABA receptor activity.

Discovery of α-Substituted Imidazole-4-acetic Acid Analogues as a Novel Class of ρ γ-Aminobutyric Acid Type A Receptor Antagonists with Effect on Retinal Vascular Tone.

The ρ-containing γ-aminobutyric acid type A receptors (GABA Rs) play an important role in controlling visual signaling. Therefore, ligands that selectively target these GABA Rs are of interest. In this study, we demonstrate that the partial GABA R agonist imidazole-4-acetic acid (IAA) is able to penetrate the blood-brain barrier in vivo; we prepared a series of α- and N-alkylated, as well as bicyclic analogues of IAA to explore the structure-activity relationship of this scaffold focusing on the acetic acid side chain of IAA.