AUT1 is a positive modulator of the voltage-gated potassium channel subtypes Kv3.1b, Kv3.2a, and Kv3.3 (EC50s = 4.7, 4.9, and 31.6 μM, respectively, in a patch-clamp assay). It is selective for Kv3.1b, Kv3.2a, and Kv3.3 over Kv1.5 and Kv7.1/minK channels but also inhibits the serotonin (5-HT) transporter, 5-HT3 receptor, and α1 subunit-containing nicotinic acetylcholine receptor (nAChR) in a panel of 26 ion channels, receptors, and transporters. AUT1 increases tetraethylammonium-induced decreases in the firing frequency and amplitude of action potentials in mouse somatosensory cortex slices when used at concentrations of 1 and 10 μM.
(5R)-5-Ethyl-3-[6-(3-methoxy-4-methylphenoxy)-3-pyridinyl]-2,4-imidazolidinedione, is a novel modulator of Kv3 potassium channels which biological studies have shown it regulates the firing of parvalbumin-positive cortical interneurons.
