Nepicastat Free Base | CAS# 173997-05-2 (free base) | dopamine beta-hydroxylase inhibitor

MedKoo Cat#: 414330 | Name: Nepicastat Free Base

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Nepicastat Free Base is an inhibitor of dopamine beta-hydroxylase, an enzyme that catalyzes the conversion of dopamine to norepinephrine. It has been studied as a possible treatment for congestive heart failure, and appears to be well tolerated as such.

Chemical Structure

Nepicastat Free Base

CAS#173997-05-2 (free base)

Theoretical Analysis

MedKoo Cat#: 414330

Name: Nepicastat Free Base

CAS#: 173997-05-2 (free base)

Chemical Formula: C14H15F2N3S

Exact Mass: 295.0955

Molecular Weight: 295.35

Elemental Analysis: C, 56.93; H, 5.12; F, 12.86; N, 14.23; S, 10.85

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Related CAS #

170151-24-3 (HCl) 173997-05-2 (free base) 195881-94-8 (HCl R isomer) 177645-08-8 (HCl hydrate)

Synonym

Nepicastat Free Base

IUPAC/Chemical Name

5-(Aminomethyl)-1-((S)-5,7-difluoro-1,2,3,4-tetrahydro-2-naphthyl)-4-imidazoline-2-thione

InChi Key

YZZVIKDAOTXDEB-JTQLQIEISA-N

InChi Code

InChI=1S/C14H15F2N3S/c15-9-3-8-4-10(1-2-12(8)13(16)5-9)19-11(6-17)7-18-14(19)20/h3,5,7,10H,1-2,4,6,17H2,(H,18,20)/t10-/m0/s1

SMILES Code

S=C1NC=C(CN)N1[C@@H]2CC3=C(C(F)=CC(F)=C3)CC2

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

To be determined

Shelf Life

>2 years if stored properly

Drug Formulation

To be determined

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Nepicastat (SYN117) is a selective, potent, and orally active inhibitor of dopamine-beta-hydroxylase.

In vitro activity:

Nepicastat produced concentration-dependent inhibition of bovine (IC50 = 8.5 +/- 0.8 nM) and human (IC50 = 9.0 +/- 0.8 nM) dopamine-beta-hydroxylase. Reference: Br J Pharmacol. 1997 Aug;121(8):1803-9. https://pubmed.ncbi.nlm.nih.gov/9283721/

In vivo activity:

Acute oral administration of nepicastat (0.3, 1, 3, 10, and 30 mg/kg) produced attenuation of the pressor and positive chronotropic responses to preganglionic sympathetic nerve stimulation (about twofold to sixfold shift in the frequency-response curve) in pithed spontaneously hypertensive rats (SHRs). In inactin-anesthetized SHRs, the antihypertensive effects of nepicastat (3 mg/kg, i.v.) were accompanied by a significant decrease in renal vascular resistance (38%), a tendency toward an increase in renal blood flow (22%), and no adverse effects on urine output and Na/K excretion. Reference: J Cardiovasc Pharmacol. 1998 Jun;31(6):963-70. https://pubmed.ncbi.nlm.nih.gov/9641484/

	Solvent	mg/mL	mM
Solubility
	DMSO	48.0	162.52

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 295.35 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. 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. 2. 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. 3. 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.

In vitro protocol:

In vivo protocol:

1. 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. 2. 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.

1: Catelas DN, Serrão MP, Soares-Da-Silva P. Effects of nepicastat upon dopamine-β-hydroxylase activity and dopamine and norepinephrine levels in the rat left ventricle, kidney, and adrenal gland. Clin Exp Hypertens. 2020;42(2):118-125. doi: 10.1080/10641963.2019.1583245. Epub 2019 Mar 1. PMID: 30821508. 2: Colombo G, Maccioni P, Vargiolu D, Loi B, Lobina C, Zaru A, Carai MA, Gessa GL. The dopamine β-hydroxylase inhibitor, nepicastat, reduces different alcohol- related behaviors in rats. Alcohol Clin Exp Res. 2014 Sep;38(9):2345-53. doi: 10.1111/acer.12520. PMID: 25257286. 3: Schroeder JP, Epps SA, Grice TW, Weinshenker D. The selective dopamine β-hydroxylase inhibitor nepicastat attenuates multiple aspects of cocaine- seeking behavior. Neuropsychopharmacology. 2013 May;38(6):1032-8. doi: 10.1038/npp.2012.267. Epub 2013 Jan 3. PMID: 23303068; PMCID: PMC3629392. 4: 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. 5: De La Garza R 2nd, Bubar MJ, Carbone CL, Moeller FG, Newton TF, Anastasio NC, Harper TA, Ware DL, Fuller MA, Holstein GJ, Jayroe JB, Bandak SI, Reiman KZ, Neale AC, Pickford LB, Cunningham KA. Evaluation of the dopamine β-hydroxylase (DβH) inhibitor nepicastat in participants who meet criteria for cocaine use disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2015 Jun 3;59:40-48. doi: 10.1016/j.pnpbp.2015.01.009. Epub 2015 Jan 17. PMID: 25602710; PMCID: PMC4777897. 6: Zaru A, Maccioni P, Colombo G, Gessa GL. The dopamine β-hydroxylase inhibitor, nepicastat, suppresses chocolate self-administration and reinstatement of chocolate seeking in rats. Br J Nutr. 2013 Oct;110(8):1524-33. doi: 10.1017/S0007114513000743. Epub 2013 Apr 8. PMID: 23561307. 7: Devoto P, Flore G, Saba P, Bini V, Gessa GL. The dopamine beta-hydroxylase inhibitor nepicastat increases dopamine release and potentiates psychostimulant- induced dopamine release in the prefrontal cortex. Addict Biol. 2014 Jul;19(4):612-22. doi: 10.1111/adb.12026. Epub 2013 Jan 7. PMID: 23289939. 8: 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. 9: Bonifácio MJ, Sousa F, Neves M, Palma N, Igreja B, Pires NM, Wright LC, Soares-da-Silva P. Characterization of the interaction of the novel antihypertensive etamicastat with human dopamine-β-hydroxylase: comparison with nepicastat. Eur J Pharmacol. 2015 Mar 15;751:50-8. doi: 10.1016/j.ejphar.2015.01.034. Epub 2015 Jan 29. PMID: 25641750. 10: Loureiro AI, Bonifácio MJ, Fernandes-Lopes C, Pires N, Igreja B, Wright LC, Soares-da-Silva P. Role of P-glycoprotein and permeability upon the brain distribution and pharmacodynamics of etamicastat: a comparison with nepicastat. Xenobiotica. 2015;45(9):828-39. doi: 10.3109/00498254.2015.1018985. Epub 2015 Jun 10. PMID: 25915108.