Studies on the mechanism of phenylethan-olamine-N-methyl-transferase inhibition by a dichloro-substituted benzimidazole

Abstract 2-Amino-5-6,-dichlorobenzimidazole (DCB) is the most potent inhibitor in vitro of phenylethanolamine- N- methyl-transferase (PNMT) known; in our laboratory its I 50 for inhibiting a partially purified rabbit adrenal enzyme preparation with norepine-phrine and S -adenosylmethionine as co-substrates was 4 × 10 −7 M. DCB was not a substrate for PNMT at concentrations encompassing its inhibitory range (10 −4 −10 −8 M) and its antagonistic effect upon the enzyme after 30 min of preincubation was reversible. Kinetically, DCB was a noncompetitive inhibitor of norepinephrine and antagonized S -adenosylmethionine uncompetitively. Thus, the inhibition produced by this compound was not surmountable by either substrate. In kinetic studies at 1 × 10 −4 M, epinephrine behaved as did DCB, which demonstrates a similarity in the mode of inhibitory action of the two compounds.