methapyrilene

Summary

Summary: Histamine H1 antagonist with sedative action used as a hypnotic and in allergies.

Top Publications

  1. Ratra G, Cottrell S, Powell C. Effects of induction and inhibition of cytochromes P450 on the hepatotoxicity of methapyrilene. Toxicol Sci. 1998;46:185-96 pubmed
    The mechanisms by which the antihistamine drug methapyrilene causes acute periportal hepatotoxicity in rats are not yet elucidated...
  2. Auman J, Chou J, Gerrish K, Huang Q, Jayadev S, Blanchard K, et al. Identification of genes implicated in methapyrilene-induced hepatotoxicity by comparing differential gene expression in target and nontarget tissue. Environ Health Perspect. 2007;115:572-8 pubmed
    ..Toxicogenomics experiments often reveal thousands of transcript alterations that are related to multiple processes, making it difficult to identify key gene changes that are related to the toxicity of interest...
  3. Craig A, Sidaway J, Holmes E, Orton T, Jackson D, Rowlinson R, et al. Systems toxicology: integrated genomic, proteomic and metabonomic analysis of methapyrilene induced hepatotoxicity in the rat. J Proteome Res. 2006;5:1586-601 pubmed
    Administration of high doses of the histamine antagonist methapyrilene to rats causes periportal liver necrosis...
  4. Hamadeh H, Knight B, Haugen A, Sieber S, Amin R, Bushel P, et al. Methapyrilene toxicity: anchorage of pathologic observations to gene expression alterations. Toxicol Pathol. 2002;30:470-82 pubmed
    b>Methapyrilene (MP) exposure of animals can result in an array of adverse pathological responses including hepatotoxicity...
  5. Ratra G, Morgan W, Mullervy J, Powell C, Wright M. Methapyrilene hepatotoxicity is associated with oxidative stress, mitochondrial disfunction and is prevented by the Ca2+ channel blocker verapamil. Toxicology. 1998;130:79-93 pubmed
    b>Methapyrilene (MP) is an unusual hepatotoxin in that it causes periportal necrosis in rats. The mechanism of acute methapyrilene hepatotoxicity has, therefore, been investigated in cultured male rat hepatocytes...
  6. Ratra G, Powell C, Park B, Maggs J, Cottrell S. Methapyrilene hepatotoxicity is associated with increased hepatic glutathione, the formation of glucuronide conjugates, and enterohepatic recirculation. Chem Biol Interact. 2000;129:279-95 pubmed
    The mechanisms by which acute administration of methapyrilene, an H(1)-receptor antihistamine causes periportal necrosis to rats are unknown...
  7. Ulrich R, Rockett J, Gibson G, Pettit S. Overview of an interlaboratory collaboration on evaluating the effects of model hepatotoxicants on hepatic gene expression. Environ Health Perspect. 2004;112:423-7 pubmed
    ..compared biological and gene expression responses in rats exposed to two model hepatotoxins--clofibrate and methapyrilene. This collaborative effort provided an unprecedented opportunity for the working group to evaluate and compare ..
  8. Waring J, Ulrich R, Flint N, Morfitt D, Kalkuhl A, Staedtler F, et al. Interlaboratory evaluation of rat hepatic gene expression changes induced by methapyrilene. Environ Health Perspect. 2004;112:439-48 pubmed
    ..Health and Environmental Sciences Institute evaluated the liver gene expression profiles of rats treated with methapyrilene (MP)...
  9. Lay J, Getek T, Kelly D, Slikker W, Korfmacher W. Fast-atom bombardment and thermospray mass spectrometry for the characterization of two glucuronide metabolites of methapyrilene. Rapid Commun Mass Spectrom. 1989;3:72-5 pubmed
    Two conjugated metabolites of methapyrilene hydrochloride isolated from mouse-hepatocytes were examined by mass spectrometry using fast-atom bombardment (FAB) and thermospray ionization...
  10. Steinmetz K, Tyson C, Meierhenry E, Spalding J, Mirsalis J. Examination of genotoxicity, toxicity and morphologic alterations in hepatocytes following in vivo or in vitro exposure to methapyrilene. Carcinogenesis. 1988;9:959-63 pubmed
    The antihistamine methapyrilene (MP) was widely used as a component of cold, allergy and sleep-aid medications in the 1970s until it was identified as a potent rat liver carcinogen...

Detail Information

Publications69

  1. Ratra G, Cottrell S, Powell C. Effects of induction and inhibition of cytochromes P450 on the hepatotoxicity of methapyrilene. Toxicol Sci. 1998;46:185-96 pubmed
    The mechanisms by which the antihistamine drug methapyrilene causes acute periportal hepatotoxicity in rats are not yet elucidated...
  2. Auman J, Chou J, Gerrish K, Huang Q, Jayadev S, Blanchard K, et al. Identification of genes implicated in methapyrilene-induced hepatotoxicity by comparing differential gene expression in target and nontarget tissue. Environ Health Perspect. 2007;115:572-8 pubmed
    ..Toxicogenomics experiments often reveal thousands of transcript alterations that are related to multiple processes, making it difficult to identify key gene changes that are related to the toxicity of interest...
  3. Craig A, Sidaway J, Holmes E, Orton T, Jackson D, Rowlinson R, et al. Systems toxicology: integrated genomic, proteomic and metabonomic analysis of methapyrilene induced hepatotoxicity in the rat. J Proteome Res. 2006;5:1586-601 pubmed
    Administration of high doses of the histamine antagonist methapyrilene to rats causes periportal liver necrosis...
  4. Hamadeh H, Knight B, Haugen A, Sieber S, Amin R, Bushel P, et al. Methapyrilene toxicity: anchorage of pathologic observations to gene expression alterations. Toxicol Pathol. 2002;30:470-82 pubmed
    b>Methapyrilene (MP) exposure of animals can result in an array of adverse pathological responses including hepatotoxicity...
  5. Ratra G, Morgan W, Mullervy J, Powell C, Wright M. Methapyrilene hepatotoxicity is associated with oxidative stress, mitochondrial disfunction and is prevented by the Ca2+ channel blocker verapamil. Toxicology. 1998;130:79-93 pubmed
    b>Methapyrilene (MP) is an unusual hepatotoxin in that it causes periportal necrosis in rats. The mechanism of acute methapyrilene hepatotoxicity has, therefore, been investigated in cultured male rat hepatocytes...
  6. Ratra G, Powell C, Park B, Maggs J, Cottrell S. Methapyrilene hepatotoxicity is associated with increased hepatic glutathione, the formation of glucuronide conjugates, and enterohepatic recirculation. Chem Biol Interact. 2000;129:279-95 pubmed
    The mechanisms by which acute administration of methapyrilene, an H(1)-receptor antihistamine causes periportal necrosis to rats are unknown...
  7. Ulrich R, Rockett J, Gibson G, Pettit S. Overview of an interlaboratory collaboration on evaluating the effects of model hepatotoxicants on hepatic gene expression. Environ Health Perspect. 2004;112:423-7 pubmed
    ..compared biological and gene expression responses in rats exposed to two model hepatotoxins--clofibrate and methapyrilene. This collaborative effort provided an unprecedented opportunity for the working group to evaluate and compare ..
  8. Waring J, Ulrich R, Flint N, Morfitt D, Kalkuhl A, Staedtler F, et al. Interlaboratory evaluation of rat hepatic gene expression changes induced by methapyrilene. Environ Health Perspect. 2004;112:439-48 pubmed
    ..Health and Environmental Sciences Institute evaluated the liver gene expression profiles of rats treated with methapyrilene (MP)...
  9. Lay J, Getek T, Kelly D, Slikker W, Korfmacher W. Fast-atom bombardment and thermospray mass spectrometry for the characterization of two glucuronide metabolites of methapyrilene. Rapid Commun Mass Spectrom. 1989;3:72-5 pubmed
    Two conjugated metabolites of methapyrilene hydrochloride isolated from mouse-hepatocytes were examined by mass spectrometry using fast-atom bombardment (FAB) and thermospray ionization...
  10. Steinmetz K, Tyson C, Meierhenry E, Spalding J, Mirsalis J. Examination of genotoxicity, toxicity and morphologic alterations in hepatocytes following in vivo or in vitro exposure to methapyrilene. Carcinogenesis. 1988;9:959-63 pubmed
    The antihistamine methapyrilene (MP) was widely used as a component of cold, allergy and sleep-aid medications in the 1970s until it was identified as a potent rat liver carcinogen...
  11. Beekman J, Boess F, Hildebrand H, Kalkuhl A, Suter L. Gene expression analysis of the hepatotoxicant methapyrilene in primary rat hepatocytes: an interlaboratory study. Environ Health Perspect. 2006;114:92-9 pubmed
    ..We evaluated gene expression patterns from cultured rat primary hepatocytes after a 24-hr incubation with methapyrilene (MP)...
  12. Wrighton S, VandenBranden M, Brown T, Van Pelt C, Thomas P, Shipley L. Modulation of rat hepatic cytochromes P450 by chronic methapyrilene treatment. Biochem Pharmacol. 1991;42:1093-7 pubmed
    The antihistaminic compound methapyrilene (MP) when chronically administered has been shown to be a rat-specific hepatocarcinogen. To examine the effects of chronic MP treatment on the hepatic microsomal cytochromes P450...
  13. Uehara T, Kiyosawa N, Hirode M, Omura K, Shimizu T, Ono A, et al. Gene expression profiling of methapyrilene-induced hepatotoxicity in rat. J Toxicol Sci. 2008;33:37-50 pubmed
    ..b>Methapyrilene (MP) 100 mg/kg produced obvious histopathological changes in liver of rats by single or repeated dose up to 28 ..
  14. Chu T, Deng S, Wolfinger R, Paules R, Hamadeh H. Cross-site comparison of gene expression data reveals high similarity. Environ Health Perspect. 2004;112:449-55 pubmed
    ..these factors by comparing high-density gene expression data sets generated on two sets of RNA from methapyrilene (MP) experiments conducted at Abbott Laboratories and Boehringer-Ingelheim Pharmaceuticals, Inc...
  15. Man W, White I, Bryant D, Bugelski P, Camilleri P, Cutler P, et al. Protein expression analysis of drug-mediated hepatotoxicity in the Sprague-Dawley rat. Proteomics. 2002;2:1577-85 pubmed
    This study has investigated the protein changes in rat liver elicited by a group of model hepatotoxicants, methapyrilene, cyproterone acetate and dexamethasone and offers a compelling argument in support of the use of two-dimensional ..
  16. Kindrat I, Dreval K, Shpyleva S, Tryndyak V, de Conti A, Mudalige T, et al. Effect of methapyrilene hydrochloride on hepatic intracellular iron metabolism in vivo and in vitro. Toxicol Lett. 2017;281:65-73 pubmed publisher
    ..In the present study, we investigated the effect of the hepatotoxicant and hepatocarcinogen methapyrilene hydrochloride on iron metabolism in rat liver in a repeat-dose in vivo toxicity study and in human HepaRG ..
  17. Hernandez L, Petropoulos C, Hughes S, Lijinsky W. DNA methylation and oncogene expression in methapyrilene-induced rat liver tumors and in treated hepatocytes in culture. Mol Carcinog. 1991;4:203-9 pubmed
    Continued exposure of rats to carcinogenic doses of methapyrilene (MP) leads to elevated levels of 5-methyl-deoxycytidine (5MC) in liver DNA...
  18. Korfmacher W, Freeman J, Hansen E, Holder C, Getek T. Characterization of the antihistamines tripelennamine, methapyrilene, and thenyldiamine and their N-oxides by thermospray mass spectrometry. J Anal Toxicol. 1989;13:94-6 pubmed
    This study describes an investigation of the thermospray (TS) mass spectrometric analysis of tripelennamine, methapyrilene, thenyldiamine, and their N-oxide derivatives...
  19. Kimura M, Mizukami S, Watanabe Y, Hasegawa Baba Y, Onda N, Yoshida T, et al. Disruption of spindle checkpoint function ahead of facilitation of cell proliferation by repeated administration of hepatocarcinogens in rats. J Toxicol Sci. 2015;40:855-71 pubmed publisher
    ..Thus, rats were repeatedly administered with hepatocarcinogens (methapyrilene, carbadox and thioacetamide), a marginal hepatocarcinogen (leucomalachite green), hepatocarcinogenic promoters ..
  20. Ozden S, Turgut Kara N, Sezerman O, Durasi Ä, Chen T, Demirel G, et al. Assessment of global and gene-specific DNA methylation in rat liver and kidney in response to non-genotoxic carcinogen exposure. Toxicol Appl Pharmacol. 2015;289:203-12 pubmed publisher
    ..of non-genotoxic hepatocarcinogens, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), hexachlorobenzene (HCB), methapyrilene (MPY) and male rat kidney carcinogens, d-limonene, p-dichlorobenzene (DCB), chloroform and ochratoxin A (OTA) ..
  21. Hernandez L, Lijinsky W. Glutathione and lipid peroxide levels in rat liver following administration of methapyrilene and analogs. Chem Biol Interact. 1989;69:217-24 pubmed
    The possibility was examined that the induction of tumors in rat liver by feeding methapyrilene, which is not mutagenic, is related to effects on glutathione levels and lipid peroxidation...
  22. Slopianka M, Herrmann A, Pavkovic M, Ellinger Ziegelbauer H, Ernst R, Mally A, et al. Quantitative targeted bile acid profiling as new markers for DILI in a model of methapyrilene-induced liver injury in rats. Toxicology. 2017;386:1-10 pubmed publisher
    ..injury, 20 specific BAs were quantitatively profiled via LC-MS/MS in plasma and liver tissue in a model of methapyrilene-induced liver injury in rats...
  23. Anderson N, Copple D, Bendele R, Probst G, Richardson F. Covalent protein modifications and gene expression changes in rodent liver following administration of methapyrilene: a study using two-dimensional electrophoresis. Fundam Appl Toxicol. 1992;18:570-80 pubmed
    The effect of methapyrilene (MP), a mitochondrial proliferator and presumed nongenotoxic carcinogen, has been examined in rodent liver by means of high-resolution two-dimensional electrophoretic analysis of total proteins...
  24. Sharma A, Hexdall A, Chang E, Nelson L, Hoffman R. Diphenhydramine-induced wide complex dysrhythmia responds to treatment with sodium bicarbonate. Am J Emerg Med. 2003;21:212-5 pubmed
    ..We describe 3 cases of diphenhydramine-induced cardiac toxicity that were responsive to bicarbonate...
  25. Greenman D, Sheldon W, Schieferstein G, Allen R, Allaben W. Triprolidine: 104-week feeding study in rats. Fundam Appl Toxicol. 1995;27:223-31 pubmed
    ..Triprolidine was not carcinogenic in F344 rats...
  26. Leitch A, Probert P, Shayman J, Meyer S, Kass G, Wright M. B-13 progenitor-derived hepatocytes (B-13/H cells) model lipid dysregulation in response to drugs and chemicals. Toxicology. 2017;386:120-132 pubmed publisher
    ..Through application of this model, hepatotoxin methapyrilene exposure was shown to induce phospholipidosis in both B-13 and B-13/H cells in a time- and dose-dependent ..
  27. Horn D, Jordan W, Holloway D, Smith W, Richardson F. Dose-dependent induction of GST-P+ staining foci by the rat hepatocarcinogen methapyrilene in the medium-term bioassay. Fundam Appl Toxicol. 1996;29:194-7 pubmed
    Previous studies have demonstrated that methapyrilene hydrochloride (MP) is a rat-specific nongenotoxic carcinogen which induces liver tumors in a dose-dependent manner following chronic exposure in the diet...
  28. Richardson F, Strom S, Copple D, Bendele R, Probst G, Anderson N. Comparisons of protein changes in human and rodent hepatocytes induced by the rat-specific carcinogen, methapyrilene. Electrophoresis. 1993;14:157-61 pubmed
    ..similarities and differences in the response of rodents and humans to the rat-specific hepatocarcinogen, methapyrilene (MP)...
  29. Albertini S, Gocke E. Phenobarbital: does the positive result in TA1535 indicate genotoxic properties?. Environ Mol Mutagen. 1992;19:161-6 pubmed
    ..Thus in the usual sense, PB is not genotoxic in the Ames test. Methapyrilene, another liver carcinogen with an assumed nongenotoxic mode of action, showed almost identical properties in ..
  30. Richardson F, Horn D, Anderson N. Dose-responses in rat hepatic protein modification and expression following exposure to the rat hepatocarcinogen methapyrilene. Carcinogenesis. 1994;15:325-9 pubmed
    Dose-related effects of methapyrilene (MP) on protein modification and expression were examined using two-dimensional gel electrophoresis (2-D PAGE) coupled with computer analysis...
  31. Cerniglia C, Hansen E, Lambert K, Korfmacher W, Miller D. Fungal transformations of antihistamines: metabolism of methapyrilene, thenyldiamine and tripelennamine to N-oxide and N-demethylated derivatives. Xenobiotica. 1988;18:301-12 pubmed
    ..Cunninghamella elegans ATCC 9245 and 36112 were tested for their ability to transform the antihistamines methapyrilene (I), thenyldiamine (II) and tripelennamine (III). 2. Antihistamine metabolites were isolated by h.p.l.c...
  32. Singer S, Lijinsky W, Kratz L, Castagnoli N, Rose J. A comparison of in vivo and in vitro metabolites of the H1-antagonist N,N-dimethyl-N'-2-pyridyl-N'-(2-thienylmethyl)-1,2-ethanediamine (methapyrilene) in the rat. Xenobiotica. 1987;17:1279-91 pubmed
    1. The H1-antagonist N,N-dimethyl-N'-2-pyridyl-N'-(2-thienylmethyl)-1,2-ethanediamine (methapyrilene) is carcinogenic in rats. 2...
  33. Lampe M, Kammerer R. Cytochrome P-450 dependent binding of methapyrilene to DNA in vitro. Carcinogenesis. 1987;8:1525-9 pubmed
    b>Methapyrilene ([14C]MPH) was found to bind to calf thymus DNA only after activation by both rat liver microsomes and NADPH...
  34. Wright M, Issa R, Smart D, Trim N, Murray G, Primrose J, et al. Gliotoxin stimulates the apoptosis of human and rat hepatic stellate cells and enhances the resolution of liver fibrosis in rats. Gastroenterology. 2001;121:685-98 pubmed
    ..Hepatic stellate cells (HSCs) play a pivotal role in liver fibrosis and stimulating their apoptosis could be an effective treatment for liver fibrosis...
  35. Priestley C, Regan S, Kevin Park B, Williams D. The genotoxic potential of methapyrilene using the alkaline Comet assay in vitro and in vivo. Toxicology. 2011;290:249-57 pubmed publisher
  36. Caldwell J. Perspective on the usefulness of the mouse lymphoma assay as an indicator of a genotoxic carcinogen: ten compounds which are positive in the mouse lymphoma assay but are not genotoxic carcinogens. Teratog Carcinog Mutagen. 1993;13:185-90 pubmed
    ..It is concluded that a positive mouse lymphoma assay alone cannot be a barrier to the human use of drugs and other chemicals...
  37. Lee H, Kim Y, Roh J. Clastogenicity of methapyrilene hydrochloride in cultured Chinese hamster cells. Mutat Res. 1994;341:77-82 pubmed
    The antihistaminic agent methapyrilene hydrochloride (MPH, CAS No. 135-23-9) has been reported as a potent rat hepatocarcinogen. However, neither the action mechanism nor mutagenicity of MPH have been clearly elucidated yet...
  38. Mercer A, Regan S, Hirst C, Graham E, Antoine D, Benson C, et al. Functional and toxicological consequences of metabolic bioactivation of methapyrilene via thiophene S-oxidation: Induction of cell defence, apoptosis and hepatic necrosis. Toxicol Appl Pharmacol. 2009;239:297-305 pubmed publisher
    b>Methapyrilene, [N,N-dimethyl-N'-pyridyl-N'(2-thienylmethyl)-1,2-ethanediamine] (MP) was withdrawn from, clinical use due to reported periportal hepatic necrosis and hepatocarcinogenicity in the rat, via S-oxidation of the thiophene group...
  39. Casciano D, Shaddock J, Talaska G. The potent hepatocarcinogen methapyrilene does not form DNA adducts in livers of Fischer 344 rats. Mutat Res. 1988;208:129-35 pubmed
    The antihistamine methapyrilene hydrochloride has been shown to be a potent hepatocarcinogen in Fischer 344 rats. It has also been evaluated in a number of short-term in vitro genotoxicity assays resulting in conflicting reports...
  40. Korfmacher W, Getek T, Hansen E, Cerniglia C. Direct analysis of microbial extracts containing metabolites of ethylenediamine-type antihistamines via high-performance liquid chromatography-thermospray mass spectrometry. Anal Biochem. 1990;185:136-42 pubmed
    ..mass spectrometry (HPLC-TSMS) for the characterization of the ethylenediamine-type antihistamines, pyrilamine, methapyrilene, tripelennamine, and thenyldiamine, and their methylene chloride-extractable microbial metabolites from a ..
  41. Casciano D, 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;263:127-32 pubmed
    The antihistamine methapyrilene hydrochloride has been shown to be a potent hepatocarcinogen in Fischer 344 rats. It has also been evaluated in a number of short-term in vivo and in vitro genotoxicity assays with conflicting results...
  42. Bryant D, Monte S, Man W, Kramer K, Bugelski P, Neville W, et al. Principal component analysis of mass spectra of peptides generated from the tryptic digestion of protein mixtures. Rapid Commun Mass Spectrom. 2001;15:418-27 pubmed
    ..Two up-regulated proteins, glutathione S-transferase with methapyrilene and peroxisomal bifunctional enzyme with SB-219994, were identified in this manner.
  43. Lampe M, Kammerer R. Species differences in the metabolism and macromolecular binding of methapyrilene: a comparison of rat, mouse and hamster. Xenobiotica. 1990;20:1269-80 pubmed
    1. The metabolism of methapyrilene (MPH) by rat, hamster and mouse liver microsomes in vitro was investigated together with the binding of 14C-MPH to calf thymus DNA after metabolic activation. 2...
  44. Ashby J, Callander R, Paton D, Zeiger E, Ratpan F. Weak and unexpected mutagenicity to Salmonella of the rat hepatocarcinogen methapyrilene. Environ Mol Mutagen. 1988;12:243-52 pubmed
    The rat liver carcinogen methapyrilene is shown to be a selective mutagen to strain TA1535 of Salmonella typhimurium when tested in the absence of S9 mix and using the standard plate-incorporation assay protocol...
  45. Schug M, Heise T, Bauer A, Storm D, Blaszkewicz M, Bedawy E, et al. Primary rat hepatocytes as in vitro system for gene expression studies: comparison of sandwich, Matrigel and 2D cultures. Arch Toxicol. 2008;82:923-31 pubmed publisher
    ..Sult1a1 that recently have been reported to be influenced by the antihistamine and non-genotoxic carcinogen methapyrilene (MPy). The most reproducible effects of MPy were observed in sandwich cultures...
  46. Lijinsky W, Kovatch R, Thomas B. The carcinogenic effect of methapyrilene combined with nitrosodiethylamine given to rats in low doses. Carcinogenesis. 1992;13:1293-7 pubmed
    The carcinogenic effects of combinations of methapyrilene hydrochloride (MP), nitrosodiethylamine (NDEA), and phenobarbital (PB) or partial hepatectomy (PH) were examined following sequential treatment of rats...
  47. Richardson F, Copple D, Eacho P. Effects of methapyrilene on DNA synthesis in mice and rats following continuous dietary exposure. Carcinogenesis. 1992;13:2453-7 pubmed
    The effects of the antihistamine methapyrilene (MP) on DNA synthesis in rats and mice were investigated. Previous studies have demonstrated a dose response for tumor induction in the rat but no carcinogenic effect in the mouse...
  48. Graham E, Walsh R, Hirst C, Maggs J, Martin S, Wild M, et al. Identification of the thiophene ring of methapyrilene as a novel bioactivation-dependent hepatic toxicophore. J Pharmacol Exp Ther. 2008;326:657-71 pubmed publisher
    b>Methapyrilene (MP), a 2-thiophene H(1)-receptor antagonist, is a model toxicant in the genomic and proteomic analyses of hepatotoxicity...
  49. Geenen S, Michopoulos F, Kenna J, Kolaja K, Westerhoff H, Wilson I. HPLC-MS/MS methods for the quantitative analysis of ophthalmic acid in rodent plasma and hepatic cell line culture medium. J Pharm Biomed Anal. 2011;54:1128-35 pubmed publisher
    ..to the determination of OA in samples obtained following the chronic administration of the rat hepatotoxin methapyrilene, where plasma OA concentrations were observed to show a weak negative correlation with those of established ..
  50. Rosenkranz H, Klopman G. Methapyrilene: DNA as a possible target. Mutat Res. 1990;245:239-43 pubmed
    The structural features contributing to the potential carcinogenicity, DNA-reactivity and genotoxicity of methapyrilene and its non-carcinogenic congener pyrilamine were examined...
  51. Glauert H, Pitot H. Effect of the antihistamine, methapyrilene, as an initiator of hepatocarcinogenesis in female rats. Cancer Lett. 1989;46:189-94 pubmed
    The antihistamine methapyrilene was examined for its ability to initiate hepatocarcinogenesis in rats...
  52. Schug M, Stöber R, Heise T, Mielke H, Gundert Remy U, Godoy P, et al. Pharmacokinetics explain in vivo/in vitro discrepancies of carcinogen-induced gene expression alterations in rat liver and cultivated hepatocytes. Arch Toxicol. 2013;87:337-45 pubmed publisher
    ..Recently, an in vivo/in vitro discrepancy has been described, whereby the non-genotoxic rat liver carcinogen methapyrilene alters the expression of the metabolizing genes SULT1A1 and ABAT, as well as the DNA damage response gene ..
  53. Shelton M, Ashby J, Demarini D. Mutation spectrum of a binary mixture of mutagens (methapyrilene and sodium azide) in strain TA1535 of Salmonella. Mutat Res. 1994;323:35-9 pubmed
    b>Methapyrilene (MP) is a rat-liver carcinogen and cocarcinogen that exhibits a narrow spectrum of mutagenic activity in Salmonella typhimurium, inducing only a 2-fold increase in revertants only in the base-substitution strain TA1535; it ..
  54. Goodsaid F, Smith R, Rosenblum I. Quantitative PCR deconstruction of discrepancies between results reported by different hybridization platforms. Environ Health Perspect. 2004;112:456-60 pubmed
    ..cDNA and Affymetrix oligo platforms used to evaluate hepatic gene expression changes in rats exposed to methapyrilene. Caldesmon cDNA platform hybridization results showed decreases in gene expression levels for the high-dose ..
  55. Heise T, Schug M, Storm D, Ellinger Ziegelbauer H, Ahr H, Hellwig B, et al. In vitro - in vivo correlation of gene expression alterations induced by liver carcinogens. Curr Med Chem. 2012;19:1721-30 pubmed
    ..livers of rats after oral administration of the liver carcinogens aflatoxin B1 (AB1), 2-nitrofluorene (2-NF), methapyrilene (MP) or piperonyl-butoxide (PBO). The functions of the 22 genes have been classified into two groups...
  56. Mally A, Chipman J. Non-genotoxic carcinogens: early effects on gap junctions, cell proliferation and apoptosis in the rat. Toxicology. 2002;180:233-48 pubmed
    ..dose-dependent effects of the non-genotoxic hepatocarcinogens Wy-14,643, 2,3,7,8-tetrachlorodibenzo-p-dioxin, methapyrilene and hexachlorobenzene and the male rat kidney carcinogens chloroform, p-dichlorobenzene and d-limonene on gap ..
  57. Kelly D, Holder C, Korfmacher W, Slikker W. Plasma elimination and urinary excretion of methapyrilene in the rat. Drug Metab Dispos. 1990;18:1018-24 pubmed
    The metabolism and elimination of methapyrilene (2-[(2-dimethylaminoethyl)-2-thenylamino]pyridine) were characterized after the iv administration of 0.7 mg/kg or 3...
  58. Turner N, Woolley J, Hozier J, Sawyer J, Clive D. Methapyrilene is a genotoxic carcinogen: studies on methapyrilene and pyrilamine in the L5178Y/TK +/- mouse lymphoma assay. Mutat Res. 1987;189:285-97 pubmed
    b>Methapyrilene (MP), a sedating antihistamine, is a potent rat hepatocarcinogen which has been thought to be non-genotoxic on the basis of the negative results in a small number of short-term mutagenicity tests...
  59. Bercu J, Jolly R, Flagella K, Baker T, Romero P, Stevens J. Toxicogenomics and cancer risk assessment: a framework for key event analysis and dose-response assessment for nongenotoxic carcinogens. Regul Toxicol Pharmacol. 2010;58:369-81 pubmed publisher
    ..be identified following short-term oral rat exposure with two nongenotoxic rodent carcinogens, fenofibrate and methapyrilene, using a benchmark dose analysis of genes aggregated in Kyoto Encyclopedia of Genes and Genomes (KEGG) ..
  60. Kelly D, Holder C, Korfmacher W, Getek T, Lay J, Casciano D, et al. Metabolism of methapyrilene by Fischer-344 rat and B6C3F1 mouse hepatocytes. Xenobiotica. 1992;22:1367-81 pubmed
    ..F344 rat and B6C3F1 mouse hepatocytes were compared for their ability to transform various concentrations of methapyrilene (MP). 2. MP metabolites were isolated and purified by h.p.l.c...
  61. Perera M, Katyal S, 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;56:774-8 pubmed
    Earlier we demonstrated that short-term feeding of methapyrilene hydrochloride (MPH) and of a choline deficient (CD) diet to rats induced peroxidative damage of microsomal membrane lipids of liver cells...
  62. Lijinsky W, Yamashita K. Lack of binding of methapyrilene and similar antihistamines to rat liver DNA examined by 32P postlabeling. Cancer Res. 1988;48:6475-7 pubmed
    The nonmutagenic carcinogen methapyrilene, together with several noncarcinogenic analogues, was administered to rats p.o. for as long as 4 wk at concentrations of 0.1%...
  63. O Brien P, Slaughter M, Polley S, Kramer K. Advantages of glutamate dehydrogenase as a blood biomarker of acute hepatic injury in rats. Lab Anim. 2002;36:313-21 pubmed
    ..injury in rats using several other models of hepatic injury, including partial hepatectomy and exposure to methapyrilene, dexamethasone, cyproterone, isoniazid, lead nitrate, and Wyeth-14643...
  64. Kammerer R, Schmitz D. Species differences in the in vitro metabolism of methapyrilene. Xenobiotica. 1987;17:1121-30 pubmed
    1. The metabolism of N,N-dimethyl-N'-(2-pyridyl)-N'-(2-thienylmethyl)-1,2- ethanediamine(methapyrilene, I) by liver microsomes from rat, guinea pig, and rabbit has been examined. 2...
  65. Uehara T, Hirode M, Ono A, Kiyosawa N, Omura K, Shimizu T, et al. A toxicogenomics approach for early assessment of potential non-genotoxic hepatocarcinogenicity of chemicals in rats. Toxicology. 2008;250:15-26 pubmed publisher
    ..As prototypic non-genotoxic hepatocarcinogens, thioacetamide (TAA) and methapyrilene (MP) were selected and 349 commonly changed genes were extracted by statistical analysis...
  66. Kammerer R, Schmitz D. A comparative in vitro metabolic study of methaphenilene and pyribenzamine. Xenobiotica. 1988;18:1085-96 pubmed
  67. Gocke E, Albertini S. Synergistic/comutagenic action in the Ames test as an indication of irrelevant positive findings. Mutat Res. 1996;350:51-7 pubmed
    ..e. DNa-damaging) properties in the Ames test...
  68. Oberly T, Scheuring J, Richardson K, Richardson F, Garriott M. The evaluation of methapyrilene for bacterial mutation with metabolic activation by Aroclor-induced, methapyrilene-induced and noninduced rat-liver S9. Mutat Res. 1993;299:77-84 pubmed
    The antihistamine methapyrilene (MP) has been shown to be a potent hepatocarcinogen in rats. However, it has demonstrated little genotoxic activity in a wide variety of short-term tests...