Nilvadipine-d4 | CAS#unknown | Nilvadipine internal standard

MedKoo Cat#: 464843 | Name: Nilvadipine-d4

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Description:

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

Nilvadipine-d4 is intended for use as an internal standard for the quantification of nilvadipine by GC- or LC-MS. Nilvadipine is a dihydropyridine L-type calcium channel blocker. It is selective for L-type over N-, P/Q-, and R-type calcium channels at 10 μM. Nilvadipine (10 mg/kg per day, p.o.) inhibits increases in systolic blood pressure induced by chronic intravenous infusion of the peptide vasoconstrictor endothelin in rats. It decreases cortical and hippocampal amyloid-β burden in the APPsw (Tg2576) and PS1/APPsw transgenic mouse models of Alzheimer's disease when administered at a dose of 0.03% (w/w) in the diet for 17 and 10 months, respectively.3 Nilvadipine (3.2 mg/kg, s.c.) reduces infarct volume in a rat model of focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO).

Chemical Structure

Nilvadipine-d4

CAS#unknown

Theoretical Analysis

MedKoo Cat#: 464843

Name: Nilvadipine-d4

CAS#: unknown

Chemical Formula: C19H15D4N3O6

Exact Mass: 389.1525

Molecular Weight: 389.40

Elemental Analysis: C, 58.61; H, 5.95; N, 10.79; O, 24.65

Price and Availability

Size	Price	Availability	Quantity
1mg	USD 550.00	2 Weeks
5mg	USD 1,650.00	2 Weeks

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Related CAS #

No Data

Synonym

Nilvadipine-d4; Nilvadipine d4; (±)-Nilvadipine-d4; (±) Nilvadipine-d4;

IUPAC/Chemical Name

5-isopropyl 3-methyl 2-cyano-6-methyl-4-(3-nitrophenyl-2,4,5,6-d4)-1,4-dihydropyridine-3,5-dicarboxylate

InChi Key

FAIIFDPAEUKBEP-KDWZCNHSSA-N

InChi Code

InChI=1S/C19H19N3O6/c1-10(2)28-19(24)15-11(3)21-14(9-20)17(18(23)27-4)16(15)12-6-5-7-13(8-12)22(25)26/h5-8,10,16,21H,1-4H3/i5D,6D,7D,8D

SMILES Code

CC1=C(C(C(C(OC)=O)=C(N1)C#N)C2=C(C([N+]([O-])=O)=C(C([2H])=C2[2H])[2H])[2H])C(OC(C)C)=O

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:

Nilvadipine-d4 is deuterium labeled Nilvadipine. Nilvadipine is a potent calcium channel antagonist.

In vitro activity:

The chemotactic activities of inflammatory cell products for rat aortic smooth muscle cells (SMC) were examined in modified Boyden chambers. The chemotaxis, irrespective of the attractants used, was strongly inhibited by nilvadipine, a potent calcium antagonist, and the IC50 values were around 1 x 10(-10) M. Reference: Atherosclerosis. 1988 Aug;72(2-3):213-9. https://pubmed.ncbi.nlm.nih.gov/2850808/

In vivo activity:

The antiatherogenic activity of FR34235 (Nilvadipine), a calcium antagonist, was examined in rabbits with carotid arteries sheathed with polyethylene cuffs, and compared with that of nifedipine, verapamil and diltiazem. FR34235 dose-dependently inhibited the cuff-induced intimal thickening, and was more potent than the other calcium antagonists, whose order of potency was nifedipine, diltiazem and verapamil. Reference: Atherosclerosis. 1987 Apr;64(2-3):255-61. https://pubmed.ncbi.nlm.nih.gov/3606723/

Preparing Stock Solutions

The following data is based on the product molecular weight 389.40 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. Iwasaki Y, Asai M, Yoshida M, Nigawara T, Kambayashi M, Oiso Y, Nakashima N. Nilvadipine inhibits nuclear factor-kappaB-dependent transcription in hepatic cells. Clin Chim Acta. 2004 Dec;350(1-2):151-7. doi: 10.1016/j.cccn.2004.07.012. PMID: 15530472. 2. Nomoto A, Mutoh S, Hagihara H, Yamaguchi I. Smooth muscle cell migration induced by inflammatory cell products and its inhibition by a potent calcium antagonist, nilvadipine. Atherosclerosis. 1988 Aug;72(2-3):213-9. doi: 10.1016/0021-9150(88)90083-4. PMID: 2850808. 3. Yamazaki H, Ohguro H, Maeda T, Maruyama I, Takano Y, Metoki T, Nakazawa M, Sawada H, Dezawa M. Preservation of retinal morphology and functions in royal college surgeons rat by nilvadipine, a Ca(2+) antagonist. Invest Ophthalmol Vis Sci. 2002 Apr;43(4):919-26. PMID: 11923229. 4. Nomoto A, Hirosumi J, Sekiguchi C, Mutoh S, Yamaguchi I, Aoki H. Antiatherogenic activity of FR34235 (Nilvadipine), a new potent calcium antagonist. Effect on cuff-induced intimal thickening of rabbit carotid artery. Atherosclerosis. 1987 Apr;64(2-3):255-61. doi: 10.1016/0021-9150(87)90253-x. PMID: 3606723.

In vitro protocol:

In vivo protocol:

1. Yamazaki H, Ohguro H, Maeda T, Maruyama I, Takano Y, Metoki T, Nakazawa M, Sawada H, Dezawa M. Preservation of retinal morphology and functions in royal college surgeons rat by nilvadipine, a Ca(2+) antagonist. Invest Ophthalmol Vis Sci. 2002 Apr;43(4):919-26. PMID: 11923229. 2. Nomoto A, Hirosumi J, Sekiguchi C, Mutoh S, Yamaguchi I, Aoki H. Antiatherogenic activity of FR34235 (Nilvadipine), a new potent calcium antagonist. Effect on cuff-induced intimal thickening of rabbit carotid artery. Atherosclerosis. 1987 Apr;64(2-3):255-61. doi: 10.1016/0021-9150(87)90253-x. PMID: 3606723.

1: Morin A, Mouzon B, Ferguson S, Paris D, Browning M, Stewart W, Mullan M, Crawford F. Nilvadipine suppresses inflammation via inhibition of P-SYK and restores spatial memory deficits in a mouse model of repetitive mild TBI. Acta Neuropathol Commun. 2020 Oct 19;8(1):166. doi: 10.1186/s40478-020-01045-x. PMID: 33076989; PMCID: PMC7574534. 2: Türkeş C, Demir Y, Beydemir Ş. Some calcium-channel blockers: kinetic and in silico studies on paraoxonase-I. J Biomol Struct Dyn. 2020 Aug 12:1-9. doi: 10.1080/07391102.2020.1806927. Epub ahead of print. PMID: 32783605. 3: Dyer AH, Lawlor B, Kennelly SP; NILVAD Study Group. Gait speed, cognition and falls in people living with mild-to-moderate Alzheimer disease: data from NILVAD. BMC Geriatr. 2020 Mar 30;20(1):117. doi: 10.1186/s12877-020-01531-w. PMID: 32228468; PMCID: PMC7106668. 4: Abdullah L, Crawford F, Tsolaki M, Börjesson-Hanson A, Olde Rikkert M, Pasquier F, Wallin A, Kennelly S, Ait-Ghezala G, Paris D, Hendrix S, Blennow K, Lawlor B, Mullan M. The Influence of Baseline Alzheimer's Disease Severity on Cognitive Decline and CSF Biomarkers in the NILVAD Trial. Front Neurol. 2020 Mar 6;11:149. doi: 10.3389/fneur.2020.00149. PMID: 32210906; PMCID: PMC7067750. 5: Türkeş C, Demir Y, Beydemir Ş. Calcium channel blockers: molecular docking and inhibition studies on carbonic anhydrase I and II isoenzymes. J Biomol Struct Dyn. 2021 Mar;39(5):1672-1680. doi: 10.1080/07391102.2020.1736631. Epub 2020 Mar 9. PMID: 32107977. 6: Dyer AH, Murphy C, Segurado R, Lawlor B, Kennelly SP; NILVAD Study Group. Is Ongoing Anticholinergic Burden Associated With Greater Cognitive Decline and Dementia Severity in Mild to Moderate Alzheimer's Disease? J Gerontol A Biol Sci Med Sci. 2020 Apr 17;75(5):987-994. doi: 10.1093/gerona/glz244. PMID: 31613323. 7: Dyer AH, Murphy C, Lawlor B, Kennelly SP; NILVAD Study Group. Cognitive Outcomes of Long-term Benzodiazepine and Related Drug (BDZR) Use in People Living With Mild to Moderate Alzheimer's Disease: Results From NILVAD. J Am Med Dir Assoc. 2020 Feb;21(2):194-200. doi: 10.1016/j.jamda.2019.08.006. Epub 2019 Oct 8. PMID: 31604674. 8: de Heus RAA, Olde Rikkert MGM, Tully PJ, Lawlor BA, Claassen JAHR; NILVAD Study Group. Blood Pressure Variability and Progression of Clinical Alzheimer Disease. Hypertension. 2019 Nov;74(5):1172-1180. doi: 10.1161/HYPERTENSIONAHA.119.13664. Epub 2019 Sep 23. PMID: 31542965. 9: de Jong DLK, de Heus RAA, Rijpma A, Donders R, Olde Rikkert MGM, Günther M, Lawlor BA, van Osch MJP, Claassen JAHR. Effects of Nilvadipine on Cerebral Blood Flow in Patients With Alzheimer Disease. Hypertension. 2019 Aug;74(2):413-420. doi: 10.1161/HYPERTENSIONAHA.119.12892. Epub 2019 Jun 17. PMID: 31203725. 10: de Heus RAA, Donders R, Santoso AMM, Olde Rikkert MGM, Lawlor BA, Claassen JAHR; Nilvad Study Group. Blood Pressure Lowering With Nilvadipine in Patients With Mild-to-Moderate Alzheimer Disease Does Not Increase the Prevalence of Orthostatic Hypotension. J Am Heart Assoc. 2019 May 21;8(10):e011938. doi: 10.1161/JAHA.119.011938. PMID: 31088188; PMCID: PMC6585342. 11: Türkeş C, Demir Y, Beydemir Ş. Anti-diabetic Properties of Calcium Channel Blockers: Inhibition Effects on Aldose Reductase Enzyme Activity. Appl Biochem Biotechnol. 2019 Sep;189(1):318-329. doi: 10.1007/s12010-019-03009-x. Epub 2019 Apr 13. PMID: 30980289. 12: Ikemura N, Yamaori S, Kobayashi C, Kamijo S, Murayama N, Yamazaki H, Ohmori S. Inhibitory effects of antihypertensive drugs on human cytochrome P450 2J2 activity: Potent inhibition by azelnidipine and manidipine. Chem Biol Interact. 2019 Jun 1;306:1-9. doi: 10.1016/j.cbi.2019.04.005. Epub 2019 Apr 6. PMID: 30965050. 13: Ježíková Z, Pagáč T, Víglaš J, Pfeiferová B, Šoltys K, Bujdáková H, Černáková L, Olejníková P. Synergy Over Monotherapy. Curr Microbiol. 2019 Jun;76(6):673-677. doi: 10.1007/s00284-019-01678-9. Epub 2019 Apr 2. PMID: 30941538. 14: Saboo S, Mugheirbi NA, Zemlyanov DY, Kestur US, Taylor LS. Congruent release of drug and polymer: A "sweet spot" in the dissolution of amorphous solid dispersions. J Control Release. 2019 Mar 28;298:68-82. doi: 10.1016/j.jconrel.2019.01.039. Epub 2019 Feb 4. PMID: 30731151. 15: Morin A, Mouzon B, Ferguson S, Paris D, Saltiel N, Lungmus C, Mullan M, Crawford F. Treatment With Nilvadipine Mitigates Inflammatory Pathology and Improves Spatial Memory in Aged hTau Mice After Repetitive Mild TBI. Front Aging Neurosci. 2018 Oct 11;10:292. doi: 10.3389/fnagi.2018.00292. PMID: 30364309; PMCID: PMC6193195. 16: Lawlor B, Segurado R, Kennelly S, Olde Rikkert MGM, Howard R, Pasquier F, Börjesson-Hanson A, Tsolaki M, Lucca U, Molloy DW, Coen R, Riepe MW, Kálmán J, Kenny RA, Cregg F, O'Dwyer S, Walsh C, Adams J, Banzi R, Breuilh L, Daly L, Hendrix S, Aisen P, Gaynor S, Sheikhi A, Taekema DG, Verhey FR, Nemni R, Nobili F, Franceschi M, Frisoni G, Zanetti O, Konsta A, Anastasios O, Nenopoulou S, Tsolaki-Tagaraki F, Pakaski M, Dereeper O, de la Sayette V, Sénéchal O, Lavenu I, Devendeville A, Calais G, Crawford F, Mullan M; NILVAD Study Group. Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial. PLoS Med. 2018 Sep 24;15(9):e1002660. doi: 10.1371/journal.pmed.1002660. PMID: 30248105; PMCID: PMC6152871. 17: Hori T, Ouchi M, Otani N, Nohara M, Morita A, Otsuka Y, Jutabha P, Shibasaki I, Matsushita Y, Fujita T, Fukuda H, Anzai N. The uricosuric effects of dihydropyridine calcium channel blockers in vivo using urate under-excretion animal models. J Pharmacol Sci. 2018 Apr;136(4):196-202. doi: 10.1016/j.jphs.2017.11.011. Epub 2018 Mar 8. PMID: 29656005. 18: Atkin TA, Maher CM, Gerlach AC, Gay BC, Antonio BM, Santos SC, Padilla KM, Rader J, Krafte DS, Fox MA, Stewart GR, Petrovski S, Devinsky O, Might M, Petrou S, Goldstein DB. A comprehensive approach to identifying repurposed drugs to treat SCN8A epilepsy. Epilepsia. 2018 Apr;59(4):802-813. doi: 10.1111/epi.14037. Epub 2018 Mar 25. PMID: 29574705. 19: Sahoo AK, Dandapat J, Dash UC, Kanhar S. Features and outcomes of drugs for combination therapy as multi-targets strategy to combat Alzheimer's disease. J Ethnopharmacol. 2018 Apr 6;215:42-73. doi: 10.1016/j.jep.2017.12.015. Epub 2017 Dec 14. PMID: 29248451. 20: Deguchi S, Otake H, Nakazawa Y, Hiramatsu N, Yamamoto N, Nagai N. Ophthalmic Formulation Containing Nilvadipine Nanoparticles Prevents Retinal Dysfunction in Rats Injected with Streptozotocin. Int J Mol Sci. 2017 Dec 15;18(12):2720. doi: 10.3390/ijms18122720. PMID: 29244747; PMCID: PMC5751321.