JNJ-26489112 is a CNS-active agent and inhibitor of voltage-gated Na+ channels and N-type Ca2+ channels with broad-spectrum anticonvulsant activity in rodents and can be used to study neurological disorders.

N-type channel activity:70 μM, calcium inward flow:34 μM

JNJ-26489112 inhibited calcium inward flow under depolarizing conditions (fluorescence assay) with an IC50 value of 34 μM. When N-type channel activity was measured directly by whole-cell patch-clamp assay with low-frequency stimulation (0.07 Hz), JNJ-26489112 enhanced its inhibitory effect in a concentration-dependent manner with an IC50 of 70 μM. This compound is an activator of KCNQ2 channels, especially at -50 mV. [1]

Intraperitoneal injection of JNJ-26489112 effectively prevented forelimb clonic seizures induced by bisuccinic acid (Bic), picric acid (Pic), or pentylenetetrazole (PTZ) in male CF-1 mice, with 1-hour ED50s of 197, 189, and 109 mg/kg.[1]
In a pharmacokinetic study, after oral administration of 10 mg/kg JNJ-26489112 to adult male rats, plasma Cmax was 9090 ng/mL (33 μM), tmax was 53 minutes, bioavailability (F) was 95%, t1/2 was 8.2 hours, and the AUC (total exposure) was 53,200 ng-h/mL. At doses of 10, 30, and 300 mg/kg, a linear relationship between exposure and dose was observed. The volume of distribution (Vdss) was 390 mL/kg and clearance (CL) was 96 mL/h/kg after intravenous injection of 2 mg/kg.
In female beagles, after oral administration of 10 mg/kg JNJ-26489112, Cmax reached 11,500 ng/mL (41 μM), tmax was 55 minutes, F was 83%, t1/2 was 20 hours, and the AUC was 212,000 ng-h/mL. after intravenous administration of 2 mg/kg, Vdss and CL were 630 mL/kg and 30 mL/h/kg, respectively.[1]