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Kinetics, mechanism and inhibition of monoamine oxidase
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dc.contributor.author | Ramsay, Rona R. | |
dc.contributor.author | Albreht, Alen | |
dc.date.accessioned | 2019-03-07T00:37:51Z | |
dc.date.available | 2019-03-07T00:37:51Z | |
dc.date.issued | 2018-11 | |
dc.identifier.citation | Ramsay , R R & Albreht , A 2018 , ' Kinetics, mechanism and inhibition of monoamine oxidase ' , Journal of Neural Transmission , vol. 125 , no. 11 , pp. 1659–1683 . https://doi.org/10.1007/s00702-018-1861-9 | en |
dc.identifier.issn | 0300-9564 | |
dc.identifier.other | PURE: 252404764 | |
dc.identifier.other | PURE UUID: a2434b96-5335-4462-96a0-607b7c8258b5 | |
dc.identifier.other | Scopus: 85042934061 | |
dc.identifier.other | WOS: 000449118500011 | |
dc.identifier.uri | https://hdl.handle.net/10023/17231 | |
dc.description | Funding: EU COST Action CM1103. | en |
dc.description.abstract | Monoamine oxidases (MAOs) catalyse the oxidation of neurotransmitter amines and a wide variety of primary, secondary and tertiary amine xenobiotics, including therapeutic drugs. While inhibition of MAO activity in the periphery removes protection from biogenic amines and so is undesirable, inhibition in the brain gives vital anti-depressant and behavioural advantages that make MAO a major pharmaceutical target for inhibitor design. In neurodegenerative diseases, MAO inhibitors can help maintain neurotransmitter levels, making it a common feature in novel multi-target combinations designed to combat Alzheimer’s disease, albeit not yet proven clinically. Vital information for inhibitor design comes from an understanding of the structure, mechanism and kinetics of the catalyst. This review will summarize the kinetic behaviour of MAO A and B and the kinetic evaluation of reversible inhibitors that transiently decrease catalysis. Kinetic parameters and crystal structures have enabled computational approaches to ligand discovery and validation of hits by docking. Kinetics and a wide variety of substrates and inhibitors along with theoretical modeling have also contributed to proposed schemes for the still debated chemical mechanism of amine oxidation, However, most of the marketed MAO drugs are long-lasting irreversible inactivators. The mechanism of irreversible inhibition by hydrazine, cyclopropylamine and propargylamine drugs will be discussed. The article finishes with some examples of the propargylamine moiety in multi-target ligand design to combat neurodegeneration. | |
dc.format.extent | 25 | |
dc.language.iso | eng | |
dc.relation.ispartof | Journal of Neural Transmission | en |
dc.rights | © 2018, Springer-Verlag GmbH Austria, part of Springer Nature. This work has been made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at https://doi.org/10.1007/s00702-018-1861-9 | en |
dc.subject | Enzyme kinetics | en |
dc.subject | Irreversible inhibition | en |
dc.subject | Multi-target drug design | en |
dc.subject | Monoamine neurotransmitters | en |
dc.subject | Computation and modelling | en |
dc.subject | Chemical mechanism | en |
dc.subject | QD Chemistry | en |
dc.subject | QH301 Biology | en |
dc.subject | RM Therapeutics. Pharmacology | en |
dc.subject | Chemistry(all) | en |
dc.subject | Analytical Chemistry | en |
dc.subject | Biochemistry | en |
dc.subject | Drug Discovery | en |
dc.subject.lcc | QD | en |
dc.subject.lcc | QH301 | en |
dc.subject.lcc | RM | en |
dc.title | Kinetics, mechanism and inhibition of monoamine oxidase | en |
dc.type | Journal item | en |
dc.contributor.sponsor | European Commission | en |
dc.description.version | Postprint | en |
dc.contributor.institution | University of St Andrews. School of Biology | en |
dc.contributor.institution | University of St Andrews. Biomedical Sciences Research Complex | en |
dc.identifier.doi | https://doi.org/10.1007/s00702-018-1861-9 | |
dc.description.status | Peer reviewed | en |
dc.date.embargoedUntil | 2019-03-07 | |
dc.identifier.grantnumber | oc-2010-2-8526 | en |
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