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dc.contributor.authorHagenow, Stefanie
dc.contributor.authorStasiak, A.
dc.contributor.authorRamsay, Rona R.
dc.contributor.authorStark, Holger
dc.date.accessioned2017-01-13T13:30:11Z
dc.date.available2017-01-13T13:30:11Z
dc.date.issued2017-01-13
dc.identifier.citationHagenow , S , Stasiak , A , Ramsay , R R & Stark , H 2017 , ' Ciproxifan, a H 3 receptor inverse agonist, reversibly inhibits human monoamine oxidase A and B ' Scientific Reports , vol. 7 , 40541 . DOI: 10.1038/srep40541en
dc.identifier.issn2045-2322
dc.identifier.otherPURE: 248138966
dc.identifier.otherPURE UUID: 20421b1f-1082-4982-bbb0-90660334c8ae
dc.identifier.otherScopus: 85009503928
dc.identifier.urihttp://hdl.handle.net/10023/10096
dc.descriptionSupport was kindly provided by the EU COST Actions CM1103 and CA15135 as well by DFG INST 208/664-1 FUGG and the Polish National Science Centre HARMONY 2012/04/M/N24/00212.en
dc.description.abstractCiproxifan is a well-investigated histamine H3 receptor (H3R) inverse agonist/antagonist, showing an exclusively high species-specific affinity at rodent compared to human H3R. It is well studied as reference compound for H3R in rodent models for neurological diseases connected with neurotransmitter dysregulation, e.g. attention deficit hyperactivity disorder or Alzheimer’s disease. In a screening for potential monoamine oxidase A and B inhibition ciproxifan showed efficacy on both enzyme isoforms. Further characterization of ciproxifan revealed IC50 values in a micromolar concentration range for human and rat monoamine oxidases with slight preference for monoamine oxidase B in both species. The inhibition by ciproxifan was reversible for both human isoforms. Regarding inhibitory potency of ciproxifan on rat brain MAO, these findings should be considered, when using high doses in rat models for neurological diseases. As the H3R and monoamine oxidases are all capable of affecting neurotransmitter modulation in brain, we consider dual targeting ligands as interesting approach for treatment of neurological disorders. Since ciproxifan shows only moderate activity at human targets, further investigations in animals are not of primary interest. On the other hand, it may serve as starting point for the development of dual targeting ligands.en
dc.format.extent6en
dc.language.isoeng
dc.relation.ispartofScientific Reportsen
dc.rightsCopyright the Authors, 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/en
dc.subjectHistamine H3 receptorsen
dc.subjectMonoamine oxidaseen
dc.subjectInverse agonist/antagonisten
dc.subjectDual-target liganden
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.subjectRM Therapeutics. Pharmacologyen
dc.subjectPharmacologyen
dc.subjectNDASen
dc.subject.lccRC0321en
dc.subject.lccRMen
dc.titleCiproxifan, a H3 receptor inverse agonist, reversibly inhibits human monoamine oxidase A and Ben
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.1038/srep40541
dc.description.statusPeer revieweden


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