Differential Inhibition of Neuronal and Extraneuronal Monoamine Oxidase

Abstract

This study examined whether the neuronal and extraneuronal sites of action of two monoamine oxidase (MAO) inhibitors, l-deprenyl and debrisoquin, could be distinguished by their effects on plasma concentrations of catecholamine metabolites. Plasma concentrations of the intraneuronal deaminated metabolite of norepinephrine, dihydroxyphenylglycol (DHPG), were decreased by 77% after debrisoquin and by 64% after l-deprenyl administration. Plasma concentrations of the extraneuronal O-methylated metabolite of norepinephrine, normetanephrine, were increased substantially more during treatment with l-deprenyl than with debrisoquin (255% compared to a 27% increase). The comparable decreases in plasma concentrations of DHPG indicate a similar inhibition of intraneuronal MAO by both drugs. Much larger increases in normetanephrine after l-deprenyl than after debrisoquin are consistent with a site of action of the latter drug directed at the neuronal rather than the extraneuronal compartment. Thus, differential changes in deaminated and O-methylated amine metabolites allows identification of neuronal and extraneuronal sites of action of MAO inhibitors.

Author information

Correspondence to Graeme Eisenhofer Ph.D.

Rights and permissions

Reprints and Permissions

About this article

Keywords

  • Monoamine oxidase
  • Monoamine oxidase inhibitors
  • Catecholamines
  • Metabolism
  • Norepinephrine
  • Normetanephrine

Further reading