Research Article Open Access

On the Hormetic Behaviour of Drugs Binding to Different Redox States of Amine Oxidase Enzymes

Deepak Narang1, G. Reid McDonald1, David J. Smith2, Maria Luisa Di Paolo3, Dale E. Edmondson4 and Andrew Holt1
  • 1 University of Alberta, Canada
  • 2 Tykistökatu 6, Finland
  • 3 University of Padua, Italy
  • 4 Emory University School of Medicine, United States

Abstract

Classical monoamine oxidases and copper-containing semicarbazide-sensitive amine oxidases are drug targets for a variety of established and novel pharmaceuticals used to treat conditions such as depression, Parkinsonism and inflammatory disorders. Development of enzyme inhibitors, both historically and currently, assumes an underlying adherence of these enzymes to Michaelis-Menten kinetic principles. In this mini-review, we discuss historical data from several laboratories and novel data from our own laboratories which show clearly that such an assumption is invalid. Rather, these enzymes often display hormetic behaviour towards their substrates, resulting in bell-shaped kinetic plots. We outline possible underlying mechanisms which might account for this behaviour and show how novel reversible hormetic drugs may capitalise on these mechanisms to introduce a new dimension in selectivity. The potential future benefits for therapeutic modulation of amine oxidase activities are discussed.

American Journal of Pharmacology and Toxicology
Volume 3 No. 1, 2008, 125-136

DOI: https://doi.org/10.3844/ajptsp.2008.125.136

Submitted On: 21 April 2008 Published On: 31 March 2008

How to Cite: Narang, D., McDonald, G. R., Smith, D. J., Di Paolo, M. L., Edmondson, D. E. & Holt, A. (2008). On the Hormetic Behaviour of Drugs Binding to Different Redox States of Amine Oxidase Enzymes. American Journal of Pharmacology and Toxicology, 3(1), 125-136. https://doi.org/10.3844/ajptsp.2008.125.136

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Keywords

  • enzyme kinetics
  • amine oxidases
  • substrates
  • imidazolines
  • cations