Methapyrilene HCl | CAS#135-23-9 | Histamine H1 receptor antagonist

MedKoo Cat#: 341569 | Name: Methapyrilene HCl

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Description:

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

Methapyrilene is a histamine H1 receptor antagonist (Ki = 4.5 nM) and non-genotoxic carcinogen. Dietary administration of methapyrilene (0.1%) induces liver tumors in rats, with greater than 50% of rats incurring distant metastases. It decreases the acetylation of histone 3 lysine 9 (H3K9) and H3K56, as well as the di- and trimethylation of H3K4 and H4K20, respectively, in rat liver when administered at 40 mg/kg per day for six weeks. Methapyrilene also increases 4-hydroxy nonenal (4-NHE) protein adducts in rat liver. Formulations containing methapyrilene were previously used as sleep aids.

Chemical Structure

Methapyrilene HCl

CAS#135-23-9

Theoretical Analysis

MedKoo Cat#: 341569

Name: Methapyrilene HCl

CAS#: 135-23-9

Chemical Formula: C14H20ClN3S

Exact Mass: 297.1066

Molecular Weight: 297.85

Elemental Analysis: C, 56.46; H, 6.77; Cl, 11.90; N, 14.11; S, 10.76

Price and Availability

Size	Price	Availability	Quantity
100mg	USD 285.00	2 Weeks
250mg	USD 550.00	2 Weeks

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Synonym

Methapyrilene hydrochloride; Methapyrilene HCl; Coryzol; Teralin;

IUPAC/Chemical Name

1,2-Ethanediamine, N,N-dimethyl-N'-2-pyridinyl-N'-(2-thienylmethyl)-, monohydrochloride

InChi Key

BONORRGKLJBGRV-UHFFFAOYSA-N

InChi Code

InChI=1S/C14H19N3S.ClH/c1-16(2)9-10-17(12-13-6-5-11-18-13)14-7-3-4-8-15-14;/h3-8,11H,9-10,12H2,1-2H3;1H

SMILES Code

CN(C)CCN(C1=NC=CC=C1)CC2=CC=CS2.[H]Cl

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

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

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

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Product Data

Product Data

Instruction

View handling instruction

Biological target:

Methapyrilene (Thenylpyramine) hydrochloride is an orally active H1-receptor antihistamine.

In vitro activity:

A decrease in the level of TF (transferrin) and an increase in the level of FTL (ferritin, light chain) also occurred in methapyrilene-treated differentiated HepaRG cells, indicating the existence of interspecies and in vitro-in vivo similarities in the disturbance of cellular iron homeostasis upon liver injury. Reference: Toxicol Lett. 2017 Nov 5;281:65-73. https://pubmed.ncbi.nlm.nih.gov/28935588/

In vivo activity:

Administration of high doses of the histamine antagonist methapyrilene to rats causes periportal liver necrosis. Male rats were dosed with methapyrilene for 3 days at 150 mg/kg/day, which was sufficient to induce liver necrosis, or a subtoxic dose of 50 mg/kg/day. Urine was collected over 24 h each day, while blood and liver tissues were obtained at 2 h after the final dose. The resulting data further define the changes that occur in signal transduction and metabolic pathways during methapyrilene hepatotoxicity, revealing modification of expression levels of genes and proteins associated with oxidative stress and a change in energy usage that is reflected in both gene/protein expression patterns and metabolites. Reference: J Proteome Res. 2006 Jul;5(7):1586-601. https://pubmed.ncbi.nlm.nih.gov/16823966/

	Solvent	mg/mL	mM
Solubility
	DMF	15.0	50.36
	DMSO	10.0	33.57
	Ethanol	1.0	3.36
	PBS (pH 7.2)	1.0	3.36

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 297.85 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. Braeuning A, Oberemm A, Heise T, Gundert-Remy U, Hengstler JG, Lampen A. In vitro proteomic analysis of methapyrilene toxicity in rat hepatocytes reveals effects on intermediary metabolism. Arch Toxicol. 2019 Feb;93(2):369-383. doi: 10.1007/s00204-018-2360-3. Epub 2018 Nov 22. PMID: 30467583. 2. Kindrat I, Dreval K, Shpyleva S, Tryndyak V, de Conti A, Mudalige TK, Chen T, Erstenyuk AM, Beland FA, Pogribny IP. Effect of methapyrilene hydrochloride on hepatic intracellular iron metabolism in vivo and in vitro. Toxicol Lett. 2017 Nov 5;281:65-73. doi: 10.1016/j.toxlet.2017.09.011. Epub 2017 Sep 19. PMID: 28935588. 3. Slopianka M, Herrmann A, Pavkovic M, Ellinger-Ziegelbauer H, Ernst R, Mally A, Keck M, Riefke B. Quantitative targeted bile acid profiling as new markers for DILI in a model of methapyrilene-induced liver injury in rats. Toxicology. 2017 Jul 1;386:1-10. doi: 10.1016/j.tox.2017.05.009. Epub 2017 May 19. PMID: 28529062. 4. Craig A, Sidaway J, Holmes E, Orton T, Jackson D, Rowlinson R, Nickson J, Tonge R, Wilson I, Nicholson J. Systems toxicology: integrated genomic, proteomic and metabonomic analysis of methapyrilene induced hepatotoxicity in the rat. J Proteome Res. 2006 Jul;5(7):1586-601. doi: 10.1021/pr0503376. PMID: 16823966.

In vitro protocol:

In vivo protocol:

1. Slopianka M, Herrmann A, Pavkovic M, Ellinger-Ziegelbauer H, Ernst R, Mally A, Keck M, Riefke B. Quantitative targeted bile acid profiling as new markers for DILI in a model of methapyrilene-induced liver injury in rats. Toxicology. 2017 Jul 1;386:1-10. doi: 10.1016/j.tox.2017.05.009. Epub 2017 May 19. PMID: 28529062. 2. Craig A, Sidaway J, Holmes E, Orton T, Jackson D, Rowlinson R, Nickson J, Tonge R, Wilson I, Nicholson J. Systems toxicology: integrated genomic, proteomic and metabonomic analysis of methapyrilene induced hepatotoxicity in the rat. J Proteome Res. 2006 Jul;5(7):1586-601. doi: 10.1021/pr0503376. PMID: 16823966.

1: Kindrat I, Dreval K, Shpyleva S, Tryndyak V, de Conti A, Mudalige TK, Chen T, Erstenyuk AM, Beland FA, Pogribny IP. Effect of methapyrilene hydrochloride on hepatic intracellular iron metabolism in vivo and in vitro. Toxicol Lett. 2017 Nov 5;281:65-73. doi: 10.1016/j.toxlet.2017.09.011. Epub 2017 Sep 19. PubMed PMID: 28935588. 2: Inoue K, Ochi A, Koda A, Wako Y, Kawasako K, Doi T. The 14-day repeated dose liver micronucleus test with methapyrilene hydrochloride using young adult rats. Mutat Res Genet Toxicol Environ Mutagen. 2015 Mar;780-781:123-7. doi: 10.1016/j.mrgentox.2014.04.004. Epub 2014 Apr 24. PubMed PMID: 24768639. 3: Doktorova TY, Ates G, Vinken M, Vanhaecke T, Rogiers V. Way forward in case of a false positive in vitro genotoxicity result for a cosmetic substance? Toxicol In Vitro. 2014 Feb;28(1):54-9. doi: 10.1016/j.tiv.2013.09.022. Epub 2013 Oct 2. PubMed PMID: 24095862. 4: Yafune A, Taniai E, Morita R, Akane H, Kimura M, Mitsumori K, Shibutani M. Immunohistochemical cellular distribution of proteins related to M phase regulation in early proliferative lesions induced by tumor promotion in rat two-stage carcinogenesis models. Exp Toxicol Pathol. 2014 Jan;66(1):1-11. doi: 10.1016/j.etp.2013.07.001. Epub 2013 Jul 23. PubMed PMID: 23890812. 5: Taniai E, Yafune A, Kimura M, Morita R, Nakane F, Suzuki K, Mitsumori K, Shibutani M. Fluctuations in cell proliferation, apoptosis, and cell cycle regulation at the early stage of tumor promotion in rat two-stage carcinogenesis models. J Toxicol Sci. 2012;37(6):1113-26. PubMed PMID: 23208427. 6: Doktorova TY, Ellinger-Ziegelbauer H, Vinken M, Vanhaecke T, van Delft J, Kleinjans J, Ahr HJ, Rogiers V. Comparison of hepatocarcinogen-induced gene expression profiles in conventional primary rat hepatocytes with in vivo rat liver. Arch Toxicol. 2012 Sep;86(9):1399-411. doi: 10.1007/s00204-012-0847-x. Epub 2012 Apr 8. PubMed PMID: 22484513. 7: Sakai A, Sasaki K, Hayashi K, Muramatsu D, Arai S, Endou N, Kuroda S, Poth A, Bohnenberger S, Kunkelmann T, Asakura M, Hirose H, Ishii N, Mizuhashi F, Kasamoto S, Nagai M, Pant K, Bruce SW, Sly JE, Yamazaki S, Umeda M, Tanaka N. An international validation study of a Bhas 42 cell transformation assay for the prediction of chemical carcinogenicity. Mutat Res. 2011 Oct 9;725(1-2):57-77. doi: 10.1016/j.mrgentox.2011.07.006. Epub 2011 Jul 27. PubMed PMID: 21801851. 8: Wu G, Vashishtha SC, Erve JC. Characterization of glutathione conjugates of duloxetine by mass spectrometry and evaluation of in silico approaches to rationalize the site of conjugation for thiophene containing drugs. Chem Res Toxicol. 2010 Aug 16;23(8):1393-404. doi: 10.1021/tx100141d. PubMed PMID: 20669986. 9: NTP Hepatotoxicity Studies of the Liver Carcinogen Methapyrilene Hydrochloride (CAS No. 135-23-9) Administered in Feed to Male F344/N Rats. Toxic Rep Ser. 2000 Feb;46:1-C7. PubMed PMID: 11986676. 10: Horn DM, Jordan WH, Holloway DC, Smith WC, Richardson FC. Dose-dependent induction of GST-P+ staining foci by the rat hepatocarcinogen methapyrilene in the medium-term bioassay. Fundam Appl Toxicol. 1996 Feb;29(2):194-7. PubMed PMID: 8742315. 11: Greenman DL, Sheldon W, Schieferstein G, Allen R, Allaben WT. Triprolidine: 104-week feeding study in rats. Fundam Appl Toxicol. 1995 Sep;27(2):223-31. PubMed PMID: 8529817. 12: Lee HK, Kim YH, Roh JK. Clastogenicity of methapyrilene hydrochloride in cultured Chinese hamster cells. Mutat Res. 1994 Dec;341(2):77-82. Erratum in: Mutat Res 1995 Apr;342(3-4):197. PubMed PMID: 7990858. 13: Lijinsky W, Kovatch RM, Thomas BJ. The carcinogenic effect of methapyrilene combined with nitrosodiethylamine given to rats in low doses. Carcinogenesis. 1992 Jul;13(7):1293-7. PubMed PMID: 1638702. 14: Casciano DA, Talaska G, Clive D. The potent hepatocarcinogen methapyrilene induces mutations in L5178Y mouse lymphoma cells in the apparent absence of DNA adduct formation. Mutat Res. 1991 Jun;263(2):127-32. PubMed PMID: 2046705. 15: Glauert HP, Pitot HC. Effect of the antihistamine, methapyrilene, as an initiator of hepatocarcinogenesis in female rats. Cancer Lett. 1989 Aug;46(3):189-94. PubMed PMID: 2569926. 16: Hernandez L, Allen PT, Poirier LA, Lijinsky W. S-adenosylmethionine, S-adenosylhomocysteine and DNA methylation levels in the liver of rats fed methapyrilene and analogs. Carcinogenesis. 1989 Mar;10(3):557-62. PubMed PMID: 2924400. 17: Lay JO Jr, Getek TA, Kelly DW, Slikker W Jr, Korfmacher WA. Fast-atom bombardment and thermospray mass spectrometry for the characterization of two glucuronide metabolites of methapyrilene. Rapid Commun Mass Spectrom. 1989 Mar;3(3):72-5. PubMed PMID: 2520227. 18: Casciano DA, Shaddock JG, Talaska G. The potent hepatocarcinogen methapyrilene does not form DNA adducts in livers of Fischer 344 rats. Mutat Res. 1988 Jul;208(3-4):129-35. PubMed PMID: 3398863. 19: Jones CA, Huberman E, Callaham MF, Tu A, Halloween W, Pallota S, Sivak A, Lubet RA, Avery MD, Kouri RE, Spalding J, Tennant RW. An interlaboratory evaluation of the Syrian hamster embryo cell transformation assay using eighteen coded chemicals. Toxicol In Vitro. 1988;2(2):103-16. PubMed PMID: 20702344. 20: Perera MI, Katyal SL, Shinozuka H. Choline deficient diet enhances the initiating and promoting effects of methapyrilene hydrochloride in rat liver as assayed by the induction of gamma-glutamyltranspeptidase-positive hepatocyte foci. Br J Cancer. 1987 Dec;56(6):774-8. PubMed PMID: 2893639; PubMed Central PMCID: PMC2002423.