AVE-0118

AVE-0118 is a Kv1.5 potassium channel blocker and antiarrhythmic agent. AVE-0118 blocks neuronal Kv1.5 potassium channels, thereby enhancing the release of norepinephrine. AVE-0118 enhances field stimulation-induced neurogenic contraction, an effect sensitive to α1-adrenergic receptor blockade. AVE-0118 terminates persistent atrial fibrillation in some dogs. AVE-0118 is applicable to research related to atrial fibrillation and persistent atrial fibrillation^[1][2]. IC50 & Target:IC50: 1.1 μM (Kv1.5), 3.4 uM (I_to), 4.5 uM (I_KAch), 8.4 uM (I_Kr)^[1] In Vitro:AVE-0118 (0.1 μM; 20 min) does not alter basal tone or noradrenaline-induced contractions in isolated third- or fourth-order rat small mesenteric artery ring segments^[1].
AVE-0118 (0.1 μM; 20 min) significantly potentiates electrical field stimulation-induced neurogenic contractions in isolated third- or fourth-order rat small mesenteric artery ring segments, increasing the 16 Hz EFS response from 19.7% to 44.9% of maximum phenylephrine-induced tone^[1]. In Vivo:AVE-0118 (6 mg/kg; i.v.; single dose) terminates persistent atrial fibrillation in 43% of treated beagle dogs with AF-induced atrial remodeling, with sustained sinus rhythm maintained in 29% of animals^[2].