Structural features of potent inhibitors of rat kidney histamine N-methyltransferase.

Three antimalarial drugs amodiaquine, quinacrine and chloroquine were compared side-by-side with the antiseptic agent chlorhexidine and the neuromuscular blocker alcuronium for their capacity to competitively inhibit in vitro the activity of the enzyme histamine N-methyltransferase (HMT) from rat kidney over the concentration range 10(-3)-10(-8). Amodiaquine was clearly the most potent HMT inhibitor followed by quinacrine, chlorhexidine, alcuronium and chloroquine. Investigation of the structure-activity relationships by examining space-filling models revealed marked similarities in the conformations of the arrangement of three N atoms in histamine and in each of the compounds tested.