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Nepicastat HCl

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Chemical Structure| 170151-24-3 同义名 : SYN-117 hydrochloride;RS-25560-197 hydrochloride;RS 25560-197;Nepicastat (hydrochloride);Nepicastat hydrochloride
CAS号 : 170151-24-3
货号 : A148106
分子式 : C14H16ClF2N3S
纯度 : 98%
分子量 : 331.812
MDL号 : MFCD00954638
存储条件：

粉末 Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 5 mg/mL(15.07 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

H2O: 2 mg/mL(6.03 mM)
动物实验配方：

1% CMC Na+water 20 mg/mL suspension

生物活性
靶点

  • Hydroxylase

    Bovine dopamine-beta-hydroxylase, IC50:8.5 nM

    Human dopamine-beta-hydroxylase, IC50:9 nM
描述 Dopamine beta-hydroxylase is an enzyme that catalyzes the conversion of dopamine to norepinephrine. Nepicastat hydrochloride is a dopamine β-hydroxylase inhibitor with IC50 of 8.5 ± 0.8 and 9.0 ± 0.8 nM for bovine and human, respectively[3]. In vitro, Nepicastat hydrochloride exhibited selective and concentration-dependent inhibition to dopamine-β-hydroxylase in cattle and humans, with IC50 value of 8.5 nM and 9.0 nM, respectively. Nepicastat hydrochloride has quite low affinity for 12 other enzymes and 13 neurotransmitter receptors. In vivo, in the arteries, the left ventricle, and the cerebral cortex of rats with spontaneous hypertension (SHRs), Nepicastat dosage dependently decreased the level of norepinephrine, and increased the dopamine content and dopamine/norepinephrine ratio[3]. In rat brains, 50 mg/kg (i.p.) dose of Nepicastat hydrochloride led to reduction in the noradrenalin (NE), and block of the recovery of cocaine induced drug addiction [4]. In dogs with chronic heart failure, low doses of nepicastat (0.5 mg/kg) are quite suitable to prevent dysfunction and remodeling of the left ventricle (LV), and the combination of nepicastat hydrochloride and enalapril is quite suitable to use in addition to all morphological characteristics[5]. Nepicastat hydrochloride (3 mg/kg, i.v.), to be quite suitable for the use in SHRs anesthesia, plays the role of antihypertensive; it significantly reduces renal vascular resistance (38%) and increases renal blood flow (22%)[6].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.01mL

0.60mL

0.30mL

15.07mL

3.01mL

1.51mL

30.14mL

6.03mL

3.01mL
参考文献

[1]Stanley WC, Lee K, et al. Cardiovascular effects of nepicastat (RS-25560-197), a novel dopamine beta-hydroxylase inhibitor. J Cardiovasc Pharmacol. 1998 Jun;31(6):963-70.

[2]Stanley WC, Li B, et al. Catecholamine modulatory effects of nepicastat (RS-25560-197), a novel, potent and selective inhibitor of dopamine-beta-hydroxylase. Br J Pharmacol. 1997 Aug;121(8):1803-9.

[3]Stanley WC, Li B, Bonhaus DW, Johnson LG, Lee K, Porter S, Walker K, Martinez G, Eglen RM, Whiting RL, Hegde SS. Catecholamine modulatory effects of nepicastat (RS-25560-197), a novel, potent and selective inhibitor of dopamine-beta-hydroxylase. Br J Pharmacol. 1997 Aug;121(8):1803-9. doi: 10.1038/sj.bjp.0701315. PMID: 9283721; PMCID: PMC1564872.

[4]Schroeder JP, Cooper DA, Schank JR, Lyle MA, Gaval-Cruz M, Ogbonmwan YE, Pozdeyev N, Freeman KG, Iuvone PM, Edwards GL, Holmes PV, Weinshenker D. Disulfiram attenuates drug-primed reinstatement of cocaine seeking via inhibition of dopamine β-hydroxylase. Neuropsychopharmacology. 2010 Nov;35(12):2440-9. doi: 10.1038/npp.2010.127. Epub 2010 Aug 25. PMID: 20736996; PMCID: PMC2956132.

[5]Sabbah HN, Stanley WC, Sharov VG, Mishima T, Tanimura M, Benedict CR, Hegde S, Goldstein S. Effects of dopamine beta-hydroxylase inhibition with nepicastat on the progression of left ventricular dysfunction and remodeling in dogs with chronic heart failure. Circulation. 2000 Oct 17;102(16):1990-5. doi: 10.1161/01.cir.102.16.1990. PMID: 11034950.

[6]Stanley WC, Lee K, Johnson LG, Whiting RL, Eglen RM, Hegde SS. Cardiovascular effects of nepicastat (RS-25560-197), a novel dopamine beta-hydroxylase inhibitor. J Cardiovasc Pharmacol. 1998 Jun;31(6):963-70. doi: 10.1097/00005344-199806000-00023. PMID: 9641484.