title: Pyrazolones metabolites are relevant for identifying selective anaphylaxis to metamizole.
abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) are the most common cause of hypersensitivity reactions, with pyrazolones the most frequent drugs inducing selective reactions. Immediate selective hypersensitivity to pyrazolones is thought to be mediated by specific-IgE. Sensitivity of in vitro diagnostic tests is low and this may be due to the incomplete characterization of the structures involved. Here we investigated whether main metabolites of metamizole (dipyrone) in human could be involved in the immune response using the basophil activation test (BAT). We studied subjects with confirmed selective immediate hypersensitivity to metamizole and performed BAT with metamizole and its metabolites: 4-methylamino-antipyrine (MAA), 4-aminoantipyrine (AA), 4-acetylamino-antipyrine (AAA) and 4-formylamino-antipyrine (FAA). BAT results showed an increase of positive results from 37.5% to 62.5% using metamizole plus metabolites as compared with the BAT carried out only with the parent drug, demonstrating that metamizole metabolites have a role in the reaction and can induce specific basophil activation in patients with immediate hypersensitivity to this drug. Our findings indicate that pyrazolone metabolites are useful for improving the in vitro diagnosis of allergic reactions to metamizole.
authors.affiliation: Research Laboratory, IBIMA-Regional University Hospital of Malaga-UMA, Malaga, Spain.
authors.forename: Adriana
authors.initials: A
authors.lastname: Ariza
authors.affiliation: Department of Pharmacology, University of Extremadura, Caceres, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: García-Martín
authors.affiliation: Allergy Unit, IBIMA-Regional University Hospital of Malaga-UMA, Malaga, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Salas
authors.affiliation: Research Laboratory, IBIMA-Regional University Hospital of Malaga-UMA, Malaga, Spain.|BIONAND-Andalusian Centre for Nanomedicine and Biotechnology, Malaga, Spain.
authors.forename: María I
authors.initials: MI
authors.lastname: Montañez
authors.affiliation: Research Laboratory, IBIMA-Regional University Hospital of Malaga-UMA, Malaga, Spain.
authors.forename: Cristobalina
authors.initials: C
authors.lastname: Mayorga
authors.affiliation: Allergy Service, Infanta Leonor Hospital, Madrid, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Blanca-Lopez
authors.affiliation: Unidad Mixta de Investigación IIS La Fe-UPV, Hospital La Fe, Valencia, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Andreu
authors.affiliation: Research Laboratory, IBIMA-Regional University Hospital of Malaga-UMA, Malaga, Spain.
authors.forename: James
authors.initials: J
authors.lastname: Perkins
authors.affiliation: Allergy Unit, IBIMA-Regional University Hospital of Malaga-UMA, Malaga, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Blanca
authors.affiliation: Department of Pharmacology, University of Extremadura, Caceres, Spain.
authors.forename: José A G
authors.initials: JA
authors.lastname: Agúndez
authors.affiliation: Allergy Unit, IBIMA-Regional University Hospital of Malaga-UMA, Malaga, Spain.
authors.forename: María J
authors.initials: MJ
authors.lastname: Torres
mesh_terms: D000328:Adult; D000368:Aged; D000632:Aminopyrine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000675:Ampyrone / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000707:Anaphylaxis / Q000139:chemically induced* / Q000276:immunology / Q000503:physiopathology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000378:metabolism; D015549:Basophil Degranulation Test; D001491:Basophils / Q000187:drug effects* / Q000276:immunology; D001711:Biotransformation; D016022:Case-Control Studies; D004177:Dipyrone / Q000009:adverse effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D061251:Primary Cell Culture
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000632:Aminopyrine; D000675:Ampyrone; C011256:4-formylaminoantipyrine; D004177:Dipyrone; C010403:N-acetylaminoantipyrine