Apinocaltamide (ACT-709478) is an orally available and selective T-type calcium channel blocker that penetrates the blood-brain barrier (BBB) with IC50=6.4-18nM for Cav3.1, Cav3.2, and Cav3.3, and is commonly used in epilepsy research.

hKv11.1-hERG:5.5 μM, CYP3A4:51 μM, Cav 1.2:2410 nM, CYP2C19:25 μM, CYP2D6:15 μM, CYP2C8:14 μM, CYP2C9:22 μM, Cav 3.3:7.5 nM, CYP2B6:52 μM, Cav 3.1:6.4 nM, Cav 3.2:18 nM

Apinocaltamide (Compound 66b) blocks Cav3.1, Cav3.2, Cav3.3, Cav1.2 with IC50s of 6.4, 18, 7.5 and 2410 nM, respectively. Apinocaltamide also inhibits P450 enzymes with IC50s of 14, 15, 22, 25, 51 and 52 μM for CYP2C8,CYP2D6 CYP2C9, CYP2C19, CYP3A4, and CYP2B6, respectively[1]. Apinocaltamide blocks currents through hKv11.1-hERG channels with an IC50 of 5.5 μM[1]. Apinocaltamide blocks recombinant channel hCav3.3 potently with marked voltage-dependency (Kr≈1500 nM and Ki≈20 nM)[1].

In male juvenile DBA/2J mice (22–24 days old), oral administration of Apinocaltamide (100 or 300 mg/kg, given 1 or 3 hours prior to stimulation) significantly reduced the cumulative duration of absence-like seizures over the following 12 hours by 93%, indicating strong anti-absence seizure efficacy[1].