[CAS NO. 1346233-68-8] ML218
PRODUCTS SPECIFICATIONS [1346233-68-8]
DESCRIPTION [1346233-68-8]
Overview
| MDL | MFCD23704169 |
|---|---|
| Molecular Weight | 369.33 |
| Molecular Formula | C19H26Cl2N2O |
| SMILES | O=C(NC[C@@H]1[C@@]2([H])CN(CCC(C)(C)C)C[C@@]12[H])C3=CC(Cl)=CC(Cl)=C3 |
Summary
ML218 is a potent, selective and orally active T-type Ca 2+ channels (Cav3.1, Cav3.2, Cav3.3) inhibitor with IC 50 s of 310 nM and 270 nM for Cav3.2 and Cav3.3 , respectively. ML218 inhibits the burst activity in subthalamic nucleus (STN) neurons. ML218 has no significant inhibition of L- or N-type calcium channels, K ATP or hERG potassium channels. ML218 can penetrate the blood-brain barrier [1] .
IC50 & Target
IC50: 310 nM (Cav3.2), 270 nM (Cav3.3), and 150 nM (Ca 2+ flux) [1]
In Vitro
In plasma protein binding studies (equilibrium dialysis), ML218 possesses good free fraction in both rat and human. Intrinsic clearance experiments in liver microsomes indicated that ML218 is highly cleared in rat (CL int = 115 mL/min/kg), but low to moderately cleared in human liver microsomes (CL int = 12.7 mL/min/kg) [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
ML218 (0.03-30 mg/kg; oral administration; once; male Sprague-Dawley rats) treatment reverses cataleptic behavior in rats induced by a 0.75 mg/kg dose of haloperidol
[1]
.
Free brain and plasma concentrations of ML218 increases in 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)
[1]
.
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 (t
1/2
= 7 h)
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Male Sprague-Dawley rats (275-299 g) induced by haloperidol [1] |
| Dosage: | 0.03 mg/kg, 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg, 30 mg/kg |
| Administration: | Oral administration; once |
| Result: | Reversed cataleptic behavior in rats induced by a 0.75 mg/kg dose of haloperidol. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 125 mg/mL ( 338.45 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.7076 mL | 13.5380 mL | 27.0761 mL |
| 5 mM | 0.5415 mL | 2.7076 mL | 5.4152 mL |
| 10 mM | 0.2708 mL | 1.3538 mL | 2.7076 mL |
-
1.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 6.25 mg/mL (16.92 mM); Clear solution
