Comparison of some conformationally rigid benzylamine analogs as substrates for rabbit lung N-methyltransferase

7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline hydrochloride (SK&F 64139) and 8,9-dichloro-2,3,4,5-tetrahydro-1H-2-benzazepine hydrochloride (LY134046) were found to be excellent substrates for rabbit lung N-methyltransferase using S-adenosyl-L-methionine-methyl-14C as the methyl donor. These conformationally rigid analogs of benzylamine had Km values lower than, and Vmax values at least as high as, those of the physiologically occurring amines usually considered as the best substrates for this enzyme (tryptamine, N-methyltryptamine and serotonin). Since LY134046 and SK&F 64139 have high affinity as competitive inhibitors of norepinephrine N-methyltransferase, some similarity in the active site of these two enzymes is suggested.