Zamicastat

Zamicastat (BIA 5-1058) is a dopamine β-hydroxylase (DBH) inhibitor and can cross the blood-brain barrier (BBB) to cause central as well as peripheral effects. Zamicastat is also a concentration-dependent dual P-gp and BCRP inhibitor with IC50 values of 73.8 μM and 17.0 μM, respectively. Zamicastat reduces high blood pressure.

Product information

CAS Number: 1080028-80-3

Molecular Weight: 401.47

Formula: C21H21F2N3OS

Chemical Name: 5-[2-(benzylamino)ethyl]-1-[(3R)-6,8-difluoro-3,4-dihydro-2H-1-benzopyran-3-yl]-2,3-dihydro-1H-imidazole-2-thione

Smiles: FC1C=C(F)C=C2C[C@H](COC=12)N1C(=S)NC=C1CCNCC1C=CC=CC=1

InChiKey: ZSSLCFLHEFXANG-GOSISDBHSA-N

InChi: InChI=1S/C21H21F2N3OS/c22-16-8-15-9-18(13-27-20(15)19(23)10-16)26-17(12-25-21(26)28)6-7-24-11-14-4-2-1-3-5-14/h1-5,8,10,12,18,24H,6-7,9,11,13H2,(H,25,28)/t18-/m1/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 150 mg/mL (373.63 mM; Need ultrasonic).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

Following 4 hours of incubation (5, 10, 20, 50, 80, 100 μM), a significant loss of cell viability is verified with 100 μM Zamicastat (p=0.010) in MDCK-BCRP cells. No significant losses of cell viability are observed after 4 h of incubation for other concentrations in all cell lines. By decreasing the incubation period to 30 min, there is no significant loss of cell viability (p>0.05) at 100 μM in all cell lines.

In Vivo:

Zamicastat (10, 30 and 100 mg/kg/day; oral bolus, 7 days) is tested acutely against salt-induced hypertension in the Dahl SS rat. Zamicastat produces a dose-dependent decrease in blood pressure. 24 h after Zamicastat administration mean systolic blood pressure (SBP) decrease is -12.6±4.1 mm Hg (P=0.0284), -15.2±2.7 mm Hg (P=0.0026) and -19.0±3.7 mm Hg (P=0.0036) for the 10, 30, and 100 mg/kg body weight dose, respectively. Zamicastat administration also produces a significant 24-h average decrease in diastolic blood pressure (DBP) of - 14.6±3.4 mm Hg (P=0.0073) with 10 mg/kg body weight dose, -13.0±4.5 mm Hg (P=0.0347) with 30 mg/kg body weight dose and -15.0±3.1 mm Hg (P=0.0046) with 100 mg/kg body weight dose. Zamicastat administration leads to a decrease in the 24h post-dose mean arterial pressure (MAP) of -13.4±3.8 mm Hg (P=0.0162), -14.0±3.5 mm Hg (P=0.0101) and -20.6±3.7 mm Hg (P=0.0026) for the 10, 30, and 100 mg/kg body weight dose, respectively. There is a small, but significant, effect of Zamicastat on the 24-h mean heart rate (HR) post-dose for all tested doses (10 mg/kg: -19.1±3.2 beats/min, P=0.0019; 30 mg/kg: -13.0±4.5 beats/min, P=0.0347; 100 mg/kg: -21.6±6.6 beats/min, P=0.0235).

Products are for research use only. Not for human use.