Studies on SK&F 29661, an organ-specific inhibitor of phenylethanolamine N-methyltransferase.

SK&F 29661 is an effective, reversible inhibitor of both central nervous system and adrenal phenylethanolamine N-methyl-transferase in vitro; its Ki values in our standard assay systems were 6 X 10(-7) M (central nervous system) and 3 X 10(-7) M (adrenal), respectively. In vivo, the drug inhibited the conversion of [3H]norepinephrine to [3H]epinephrine in the rat adrenal gland and upon chronic administration decreased the endogenous adrenal epinephrine/norepinephrine ratio in both the rat and squirrel monkey. SK&F 29661 did not, however, reduce rat brain stem PNMT activity after systemic administration; subsequent radioautographic studies indicated that the compound did not enter the central nervous system, presumably because of its high polarity. This drug may be useful in defining the physiological importance of peripheral phenylethanolamine N-methyltransferase inhibition.