A urea derivative that acts as a potent, selective, and reversible positive allosteric modulator for the a7 subtype of neural nicotinic acetylcholine receptors (EC50 = 216nM), with no significant effect on a4B2, a3B4 and a9a10 receptors. Specifically increase a-7 nAChR-mediated channel currents and channel mean open time in cultured neurons (~1mM). However, it does neither affect ion selectivity nor unitary conductance. Shown to cross the blood-brain barrier. Causes conformational changes in the ligand binding domain of a7 nicotinic receptors that partially overlap with those caused by acetylcholine. Causes changes in cysteine accessibility at the inner beta sheet, transition zone, and agonist binding site. Also reported to potentiate agonist-evoked GABAergic postsynaptic inward currents in somatodendritic membrane of hippocampal interneurons.
Storage and Stability:Lyophilized powder may be stored at -20°C. Stable for 12 months at -20°C. Reconstitute with sterile buffer or dH2O. Aliquot to avoid repeated freezing and thawing. Store at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.
