ML218 inhibits the burst activity in the subthalamic nucleus (STN) neurons. ML218 is an effective, selective, and orally active inhibitor of T-type Ca2+ channel (Cav3.1, Cav3.2, Cav3.3) (IC50s: 310 nM and 270 nM for Cav3.2 and Cav3.3, respectively). ML218 can penetrate the blood-brain barrier. ML218 has no significant inhibition of L- or N-type calcium channels, KATP, or hERG potassium channels.

Intrinsic clearance experiments in liver microsomes indicated that ML218 is highly cleared in the rat (CLint = 115 mL/min/kg), but low to moderately cleared in human liver microsomes (CLint = 12.7 mL/min/kg). ML218 possesses good free fraction in both rat and human, in plasma protein binding studies (equilibrium dialysis) .

ML218 (0.03-30 mg/kg; oral administration; once; male Sprague-Dawley rats) treatment reverses cataleptic behavior in rats caused by a 0.75 mg/kg dose of haloperidol. Noncompartmental pharmacokinetic analysis indicates ML218 (1 mg/kg, IV) has a mean residence time (MRT) of nearly 7 h, a value which is consistent with its terminal half-life (t1/2 = 7 h). Free brain and plasma concentrations of ML218 enhances a dose proportional manner across the dose range (3 mg/kg: [plasma] = 98 nM, [brain] = 1.66 μM; 10 mg/kg: [plasma] = 282 nM, [brain] = 5.03 μM; 30 mg/kg: 1.2 μM, [brain] = 17.7 μM).

1346233-68-8

C19H26Cl2N2O

369.33

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years