XE 991 dihydrochloride

XE 991 dihydrochloride (CAS No.: 122955-13-9) is a potent small-molecule inhibitor of Kv7 (KCNQ) voltage-gated potassium channels widely used in neurophysiology and ion channel research. It effectively blocks multiple KCNQ channel subtypes, including Kv7.1 (KCNQ1), Kv7.2 (KCNQ2), and heteromeric Kv7.2/Kv7.3 channels, as well as the neuronal M-current, with inhibitory activity in the low micromolar range. By suppressing M-current, XE 991 dihydrochloride enhances neuronal excitability and neurotransmitter release, as demonstrated by increased acetylcholine release in rat brain slice preparations, highlighting its utility as a pharmacological tool to investigate cholinergic signaling and synaptic transmission. Mechanistically, it modulates membrane excitability through inhibition of KCNQ-mediated potassium conductance, thereby influencing action potential firing and neuronal responsiveness. This compound is commonly applied in electrophysiological studies, cellular assays, and in vivo models to dissect the functional roles of Kv7 channels in neurological processes, including learning, memory, and epilepsy, as well as in drug discovery efforts targeting ion channel modulation. Experimental concentrations and dosing regimens vary depending on the biological system and specific research objectives.