Differential inhibition of neuronal and extraneuronal monoamine oxidase

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.