α 2 andrenoreceptor affinity of some inhibitors of norepinephrine N-methyltransferase

Abstract

Because certain inhibitors of norepinephrine N-methyltransferase (NMT, the epinephrine-forming enzyme) are α 2 adrenoreceptor blockers, we compared the ability of various compounds to inhibit rat brain NMT activity and the binding of tritiated clonidine to rat brain membranes in vitro . There was no correlation between potency of NMT inhibition and potency of α 2 receptor antagonism (as measured by inhibition of tritiated clonidine binding) among NMT inhibitors representing several chemical classes or among members of a single class of compounds, l-aminoindans. In addition, several potent α 2 blocking drugs were essentially inactive as NMT inhibitors. These findings indicate that NMT inhibition and α 2 blockade are dissociable activities. Future development of NMT inhibitors should include this dissociation as a goal to increase the usefulness of NMT inhibitors as pharmacologic tools.