product name Nepicastat (SYN-117) HCl
Description: Nepicastat HCl , also known as SYN117 and RS-25560-197, is a potent and selective inhibitor of both bovine and human dopamine-β-hydroxylase with IC50 of 8.5 nM and 9 nM, with negligible affinity for twelve other enzymes and thirteen neurotransmitter receptors. Dopamine beta-hydroxylase is an enzyme that catalyzes the conversion of dopamine to norepinephrine. Nepicastat has been studied as a possible treatment for congestive heart failure, and appears to be well tolerated.
References: Br J Pharmacol. 1997 Aug;121(8):1803-9; J Cardiovasc Pharmacol. 1998 Jun;31(6):963-70.
331.81
Formula
C14H15F2N3S.HCl
CAS No.
170151-24-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 66 mg/mL (198.9 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: In vitro, Nepicastat hydrochloride shows the selective and concentration-dependent inhibition effects on bovine and human dopamine-beta-hydroxylase activity with IC50 of 8.5 nM and 9.0 nM, respectively. While Nepicastat hydrochloride has negligible affinity for twelve other enzymes and thirteen neurotransmitter receptors. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | In the artery, left ventricle and cerebral cortex of spontaneously hypertensive rats (SHRs), Nepicastat hydrochloride reduces noradrenaline content, and increases dopamine content and dopamine/noradrenaline ratio in a dose-dependent manner. In addition, Nepicastat hydrochloride also produces the similar effects on noradrenaline, dopamine and dopamine/noradrenaline ratio in tissues and plasma of beagle dogs. In inactin-anesthetized SHRs, Nepicastat hydrochloride (3 mg/kg, i.v.) produces the antihypertensive effects and causes a significant decrease in renal vascular resistance (38%) and an increase in renal blood flow (22%). In dogs with chronic heart failure, low-dose Nepicastat hydrochloride (0.5 mg/kg) prevents left ventricular (LV) dysfunction and remodeling, and combination therapy of Nepicastat hydrochloride and enalapril results in additional improvements in all morphological features. In rat brain, Nepicastat hydrochloride at a dose of 50 mg/kg ( i.p.) leads to the reduction of norepinephrine (NE) and blocks cocaine-primed reinstatement of cocaine seeking. |
| Animal model | Spontaneously hypertensive rats (SHRs). |
| Formulation & Dosage | Dissolved in distilled water; 100 mg/kg; p.o. |
| References | Br J Pharmacol. 1997 Aug;121(8):1803-9; J Cardiovasc Pharmacol. 1998 Jun;31(6):963-70. |
